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FOXN1

2021-05-12T15:38:36Z

OdysseusBot: Новая страница: «Forkhead box protein N1 (Winged-helix transcription factor nude) [RONU] [WHN] ==Publications== {{medline-entry |title=Thymic rejuvenation via FOXN1-reprogra...»

Forkhead box protein N1 (Winged-helix transcription factor nude) [RONU] [WHN]

==Publications==

{{medline-entry
|title=Thymic rejuvenation via [[FOXN1]]-reprogrammed embryonic fibroblasts (FREFs) to counteract age-related inflammation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32790650
|abstract=Age-associated systemic, chronic inflammation is partially attributed to increased self-autoreactivity, resulting from disruption of central tolerance in the aged, involuted thymus. This involution causally results from gradually decreased expression of the transcription factor [[FOXN1]] in thymic epithelial cells (TECs), whereas exogenous [[FOXN1]] in TECs can partially rescue age-related thymic involution. TECs induced from [[FOXN1]]-overexpressing embryonic fibroblasts can generate an ectopic de novo thymus under the kidney capsule, and intrathymic injection of naturally young TECs can lead to middle-aged thymus regrowth. Therefore, as a thymic rejuvenation strategy, we extended these 2 findings by combining them with 2 types of promoter-driven (Rosa26CreERT and FoxN1Cre) Cre-mediated [[FOXN1]]-reprogrammed embryonic fibroblasts (FREFs). We engrafted these FREFs directly into the aged murine thymus. We found substantial regrowth of the native aged thymus with rejuvenated architecture and function in both males and females, exhibiting increased thymopoiesis and reinforced thymocyte negative selection, along with reduced senescent T cells and autoreactive T cell-mediated inflammation in old mice. Therefore, this approach has preclinical significance and presents a strategy to potentially rescue decreased thymopoiesis and perturbed negative selection to substantially, albeit partially, restore defective central tolerance and reduce subclinical autoimmune symptoms in elderly people.

|keywords=* Aging
* Immunology
* Immunotherapy
* T cell development
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526556
}}
{{medline-entry
|title=Role of Bone Marrow Maturity, Insulin-Like Growth Factor 1 Receptor, and Forkhead Box Protein N1 in Thymic Involution and Rejuvenation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27145342
|abstract=Thymic involution is associated with age-related changes of the immune system. Utilizing our innovative technique of transplantation of a thymus as an isolated vascularized graft in MHC-inbred miniature swine, we have previously demonstrated that aged thymi are rejuvenated after transplantation into juvenile swine. Here we have studied the role of insulin-like growth factor (IGF) and forkhead-box protein-N1 ([[FOXN1]]) as well as bone marrow (BM) in thymic rejuvenation and involution. We examined thymic rejuvenation and involution by means of histology and flow cytometry. Thymic function was assessed by the ability to induce tolerance of allogeneic kidneys. Aged thymi were rejuvenated in a juvenile environment, and successfully induced organ tolerance, while juvenile thymi in aged recipients involuted and had a limited ability to induce tolerance. However, juvenile BM inhibited the involution process of juvenile thymi in aged recipients. An elevated expression of both [[FOXN1]] and [[IGF1]] receptors (IGF-1R) was observed in juvenile thymi and rejuvenated thymi. Juvenile BM plays a role in promoting the local thymic milieu as indicated by its ability to inhibit thymic involution in aged animals. The expression of [[FOXN1]] and IGF-1R was noted to increase under conditions that stimulated rejuvenation, suggesting that these factors are involved in thymic recovery.
|mesh-terms=* Aging
* Animals
* Bone Marrow
* Cell Differentiation
* Forkhead Transcription Factors
* Graft Survival
* Immune Tolerance
* Receptor, IGF Type 1
* Rejuvenation
* Swine
* Swine, Miniature
* Thymus Gland
|keywords=* animal models: porcine
* basic (laboratory) research/science
* bone marrow/hematopoietic stem cell transplantation
* immunobiology
* kidney transplantation/nephrology
* thymus/thymic biology
* tolerance: experimental
* translational research/science
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097038
}}
{{medline-entry
|title=Foxn1 Is Dynamically Regulated in Thymic Epithelial Cells during Embryogenesis and at the Onset of Thymic Involution.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26983083
|abstract=Thymus function requires extensive cross-talk between developing T-cells and the thymic epithelium, which consists of cortical and medullary [[TEC]]. The transcription factor [[FOXN1]] is the master regulator of [[TEC]] differentiation and function, and declining Foxn1 expression with age results in stereotypical thymic involution. Understanding of the dynamics of Foxn1 expression is, however, limited by a lack of single cell resolution data. We have generated a novel reporter of Foxn1 expression, Foxn1G, to monitor changes in Foxn1 expression during embryogenesis and involution. Our data reveal that early differentiation and maturation of cortical and medullary [[TEC]] coincides with precise sub-lineage-specific regulation of Foxn1 expression levels. We further show that initiation of thymic involution is associated with reduced c[[TEC]] functionality, and proportional expansion of [[FOXN1]]-negative [[TEC]] in both cortical and medullary sub-lineages. Cortex-specific down-regulation of Foxn1 between 1 and 3 months of age may therefore be a key driver of the early stages of age-related thymic involution.
|mesh-terms=* Aging
* Animals
* Cell Differentiation
* Cell Lineage
* Down-Regulation
* Embryonic Development
* Epithelial Cells
* Forkhead Transcription Factors
* Mice
* Thymus Gland

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794177
}}
{{medline-entry
|title=A deletion in [[FOXN1]] is associated with a syndrome characterized by congenital hypotrichosis and short life expectancy in Birman cats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25781316
|abstract=An autosomal recessive syndrome characterized by congenital hypotrichosis and short life expectancy has been described in the Birman cat breed (Felis silvestris catus). We hypothesized that a [[FOXN1]] (forkhead box N1) loss-of-function allele, associated with the nude phenotype in humans, mice and rats, may account for the syndrome observed in Birman cats. To the best of our knowledge, spontaneous mutations in [[FOXN1]] have never been described in non-human, non-rodent mammalian species. We identified a recessive c.1030_1033delCTGT deletion in [[FOXN1]] in Birman cats. This 4-bp deletion was associated with the syndrome when present in two copies. Percentage of healthy carriers in our French panel of genotyped Birman cats was estimated to be 3.2%. The deletion led to a frameshift and a premature stop codon at position 547 in the protein. In silico, the truncated [[FOXN1]] protein was predicted to lack the activation domain and critical parts of the forkhead DNA binding domain, both involved in the interaction between [[FOXN1]] and its targets, a mandatory step to promote normal hair and thymic epithelial development. Our results enlarge the panel of recessive [[FOXN1]] loss-of-function alleles described in mammals. A DNA test is available; it will help owners avoid matings at risk and should prevent the dissemination of this morbid mutation in domestic felines.
|mesh-terms=* Amino Acid Sequence
* Animals
* Binding Sites
* Cats
* Forkhead Transcription Factors
* Gene Deletion
* Gene Frequency
* Hypotrichosis
* Life Expectancy
* Molecular Sequence Data

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363148
}}
{{medline-entry
|title=Regeneration of the aged thymus by a single transcription factor.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24715454
|abstract=Thymic involution is central to the decline in immune system function that occurs with age. By regenerating the thymus, it may therefore be possible to improve the ability of the aged immune system to respond to novel antigens. Recently, diminished expression of the thymic epithelial cell ([[TEC]])-specific transcription factor Forkhead box N1 ([[FOXN1]]) has been implicated as a component of the mechanism regulating age-related involution. The effects of upregulating [[FOXN1]] function in the aged thymus are, however, unknown. Here, we show that forced, [[TEC]]-specific upregulation of [[FOXN1]] in the fully involuted thymus of aged mice results in robust thymus regeneration characterized by increased thymopoiesis and increased naive T cell output. We demonstrate that the regenerated organ closely resembles the juvenile thymus in terms of architecture and gene expression profile, and further show that this [[FOXN1]]-mediated regeneration stems from an enlarged [[TEC]] compartment, rebuilt from progenitor [[TEC]]s. Collectively, our data establish that upregulation of a single transcription factor can substantially reverse age-related thymic involution, identifying [[FOXN1]] as a specific target for improving thymus function and, thus, immune competence in patients. More widely, they demonstrate that organ regeneration in an aged mammal can be directed by manipulation of a single transcription factor, providing a provocative paradigm that may be of broad impact for regenerative biology.
|mesh-terms=* Aging
* Animals
* Cell Proliferation
* Cellular Microenvironment
* Epithelial Cells
* Forkhead Transcription Factors
* Lymphocyte Count
* Mice
* Mice, Transgenic
* Models, Animal
* Phenotype
* Regeneration
* Stem Cells
* T-Lymphocytes
* Thymus Gland
* Up-Regulation
|keywords=* FOXN1
* Mouse
* Organ regeneration
* Thymic involution
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978836
}}

FOXM1

2021-05-12T15:38:34Z

OdysseusBot: Новая страница: «Forkhead box protein M1 (Forkhead-related protein FKHL16) (Hepatocyte nuclear factor 3 forkhead homolog 11) (HFH-11) (HNF-3/fork-head homolog 11) (M-phase phospho...»

Forkhead box protein M1 (Forkhead-related protein FKHL16) (Hepatocyte nuclear factor 3 forkhead homolog 11) (HFH-11) (HNF-3/fork-head homolog 11) (M-phase phosphoprotein 2) (MPM-2 reactive phosphoprotein 2) (Transcription factor Trident) (Winged-helix factor from INS-1 cells) [FKHL16] [HFH11] [MPP2] [WIN]

==Publications==

{{medline-entry
|title=Sirtuin 6 deficiency induces endothelial cell senescence via downregulation of forkhead box M1 expression.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33171439
|abstract=Cellular senescence of endothelial cells causes vascular dysfunction, promotes atherosclerosis, and contributes to the development of age-related vascular diseases. Sirtuin 6 ([[SIRT6]]), a conserved NAD -dependent protein deacetylase, has beneficial effects against aging, despite the fact that its functional mechanisms are largely uncharacterized. Here, we show that [[SIRT6]] protects endothelial cells from senescence. [[SIRT6]] expression is progressively decreased during both oxidative stress-induced senescence and replicative senescence. [[SIRT6]] deficiency leads to endothelial dysfunction, growth arrest, and premature senescence. Using genetically engineered endothelial cell-specific [[SIRT6]] knockout mice, we also show that down-regulation of [[SIRT6]] expression in endothelial cells exacerbates vascular aging. Expression microarray analysis demonstrated that [[SIRT6]] modulates the expression of multiple genes involved in cell cycle regulation. Specifically, [[SIRT6]] appears to regulate the expression of forkhead box M1 ([[FOXM1]]), a critical transcription factor for cell cycle progression and senescence. Overexpression of [[FOXM1]] ameliorates [[SIRT6]] deficiency-induced endothelial cell senescence. In this work, we demonstrate the role of [[SIRT6]] as an anti-aging factor in the vasculature. These data may provide the basis for future novel therapeutic approaches against age-related vascular disorders.

|keywords=* FOXM1
* SIRT6
* cell cycle
* endothelial cell
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695388
}}
{{medline-entry
|title=Upregulation of [[FOXM1]] leads to diminished drug sensitivity in myeloma.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30463534
|abstract=Following up on previous work demonstrating the involvement of the transcription factor forkhead box M1 ([[FOXM1]]) in the biology and outcome of a high-risk subset of newly diagnosed multiple myeloma (nMM), this study evaluated whether [[FOXM1]] gene expression may be further upregulated upon tumor recurrence in patients with relapsed multiple myeloma (rMM). Also assessed was the hypothesis that increased levels of [[FOXM1]] diminish the sensitivity of myeloma cells to commonly used myeloma drugs, such as the proteasome inhibitor bortezomib (Bz) and the DNA intercalator doxorubicin (Dox). [[FOXM1]] message was evaluated in 88 paired myeloma samples from patients with nMM and rMM, using gene expression microarrays as measurement tool. Sources of differential gene expression were identified and outlier analyses were performed using statistical methods. Two independent human myeloma cell lines (HMCLs) containing normal levels of [[FOXM1]] ([[FOXM1]] ) or elevated levels of lentivirus-encoded [[FOXM1]] ([[FOXM1]] ) were employed to determine [[FOXM1]]-dependent changes in cell proliferation, survival, efflux-pump activity, and drug sensitivity. Levels of retinoblastoma (Rb) protein were determined with the assistance of Western blotting. Upregulation of [[FOXM1]] occurred in 61 of 88 (69%) patients with rMM, including 4 patients that exhibited > 20-fold elevated expression peaks. Increased [[FOXM1]] levels in [[FOXM1]] myeloma cells caused partial resistance to Bz (1.9-5.6 fold) and Dox (1.5-2.9 fold) in vitro, using [[FOXM1]] myeloma as control. Reduced sensitivity of [[FOXM1]] cells to Bz was confirmed in vivo using myeloma-in-mouse xenografts. [[FOXM1]]-dependent regulation of total and phosphorylated Rb agreed with a working model of myeloma suggesting that [[FOXM1]] governs both chromosomal instability (CIN) and E2F-dependent proliferation, using a mechanism that involves interaction with NIMA related kinase 2 ([[NEK2]]) and cyclin dependent kinase 6 (CDK6), respectively. These findings enhanced our understanding of the emerging [[FOXM1]] genetic network in myeloma and provided preclinical support for the therapeutic targeting of the [[FOXM1]]-[[NEK2]] and CDK4/6-Rb-E2F pathways using small-drug CDK and [[NEK2]] inhibitors. Clinical research is warranted to assess whether this approach may overcome drug resistance in [[FOXM1]] myeloma and, thereby, improve the outcome of patients in which the transcription factor is expressed at high levels.
|mesh-terms=* Animals
* Antineoplastic Agents
* Bortezomib
* Cell Line, Tumor
* Cell Proliferation
* Cell Survival
* Doxorubicin
* Drug Resistance
* Drug Tolerance
* Forkhead Box Protein M1
* Gene Expression Profiling
* Gene Expression Regulation, Neoplastic
* Humans
* Mice, Inbred NOD
* Mice, Knockout
* Mice, SCID
* Multiple Myeloma
* Up-Regulation
* Xenograft Model Antitumor Assays
|keywords=* Cellular senescence
* Plasma-cell neoplasm
* Small-drug inhibitor
* Targeted cancer therapy
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249818
}}
{{medline-entry
|title=Preclinical characterization of abemaciclib in hormone receptor positive breast cancer.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29050219
|abstract=Abemaciclib is an ATP-competitive, reversible kinase inhibitor selective for [[CDK4]] and [[CDK6]] that has shown antitumor activity as a single agent in hormone receptor positive (HR ) metastatic breast cancer in clinical trials. Here, we examined the mechanistic effects of abemaciclib treatment using [i]in vitro[/i] and [i]in vivo[/i] breast cancer models. Treatment of estrogen receptor positive (ER ) breast cancer cells with abemaciclib alone led to a decrease in phosphorylation of Rb, arrest at G1, and a decrease in cell proliferation. Moreover, abemaciclib exposure led to durable inhibition of pRb, TopoIIα expression and DNA synthesis, which were maintained after drug removal. Treatment of ER breast cancer cells also led to a senescence response as indicated by accumulation of β-galactosidase, formation of senescence-associated heterochromatin foci, and a decrease in [[FOXM1]] positive cells. Continuous exposure to abemaciclib altered breast cancer cell metabolism and induced apoptosis. In a xenograft model of ER breast cancer, abemaciclib monotherapy caused regression of tumor growth. Overall these data indicate that abemaciclib is a [[CDK4]] and [[CDK6]] inhibitor that, as a single agent, blocks breast cancer cell progression, and upon longer treatment can lead to sustained antitumor effects through the induction of senescence, apoptosis, and alteration of cellular metabolism.

|keywords=* abemaciclib
* apoptosis
* cell cycle
* hormone receptor positive breast cancer
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642494
}}
{{medline-entry
|title=Age-dependent human β cell proliferation induced by glucagon-like peptide 1 and calcineurin signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28920919
|abstract=Inadequate pancreatic β cell function underlies type 1 and type 2 diabetes mellitus. Strategies to expand functional cells have focused on discovering and controlling mechanisms that limit the proliferation of human β cells. Here, we developed an engraftment strategy to examine age-associated human islet cell replication competence and reveal mechanisms underlying age-dependent decline of β cell proliferation in human islets. We found that exendin-4 (Ex-4), an agonist of the glucagon-like peptide 1 receptor (GLP-1R), stimulates human β cell proliferation in juvenile but not adult islets. This age-dependent responsiveness does not reflect loss of GLP-1R signaling in adult islets, since Ex-4 treatment stimulated insulin secretion by both juvenile and adult human β cells. We show that the mitogenic effect of Ex-4 requires calcineurin/nuclear factor of activated T cells (NFAT) signaling. In juvenile islets, Ex-4 induced expression of calcineurin/NFAT signaling components as well as target genes for proliferation-promoting factors, including [[NFATC1]], [[FOXM1]], and [[CCNA1]]. By contrast, expression of these factors in adult islet β cells was not affected by Ex-4 exposure. These studies reveal age-dependent signaling mechanisms regulating human β cell proliferation, and identify elements that could be adapted for therapeutic expansion of human β cells.
|mesh-terms=* Adult
* Aging
* Animals
* Calcineurin
* Cyclin A1
* Exenatide
* Female
* Forkhead Box Protein M1
* Glucagon-Like Peptide 1
* Glucagon-Like Peptide-1 Receptor
* Humans
* Insulin
* Insulin Secretion
* Insulin-Secreting Cells
* Male
* Mice, Inbred NOD
* Middle Aged
* NFATC Transcription Factors
* Peptides
* Signal Transduction
* Venoms

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617654
}}
{{medline-entry
|title=[[FOXM1]] regulates proliferation, senescence and oxidative stress in keratinocytes and cancer cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27385468
|abstract=Several transcription factors, including the master regulator of the epidermis, p63, are involved in controlling human keratinocyte proliferation and differentiation. Here, we report that in normal keratinocytes, the expression of [[FOXM1]], a member of the Forkhead superfamily of transcription factors, is controlled by p63. We observe that, together with p63, [[FOXM1]] strongly contributes to the maintenance of high proliferative potential in keratinocytes, whereas its expression decreases during differentiation, as well as during replicative-induced senescence. Depletion of [[FOXM1]] is sufficient to induce keratinocyte senescence, paralleled by an increased ROS production and an inhibition of ROS-scavenger genes (SOD2, [[CAT]], [[GPX2]], PRDX). Interestingly, [[FOXM1]] expression is strongly reduced in keratinocytes isolated from old human subjects compared with young subjects. [[FOXM1]] depletion sensitizes both normal keratinocytes and squamous carcinoma cells to apoptosis and ROS-induced apoptosis. Together, these data identify [[FOXM1]] as a key regulator of ROS in normal dividing epithelial cells and suggest that squamous carcinoma cells may also use [[FOXM1]] to control oxidative stress to escape premature senescence and apoptosis.
|mesh-terms=* Carcinoma, Squamous Cell
* Cell Death
* Cell Differentiation
* Cell Line, Tumor
* Cell Proliferation
* Cellular Senescence
* Forkhead Box Protein M1
* Humans
* Keratinocytes
* Oxidative Stress
* Reactive Oxygen Species
* Skin Aging
|keywords=* FOXM1
* head and neck cancer
* oxidative stress
* p63
* senescence
* skin
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993337
}}
{{medline-entry
|title=[[MELK]]-T1, a small-molecule inhibitor of protein kinase [[MELK]], decreases DNA-damage tolerance in proliferating cancer cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26431963
|abstract=Maternal embryonic leucine zipper kinase ([[MELK]]), a serine/threonine protein kinase, has oncogenic properties and is overexpressed in many cancer cells. The oncogenic function of [[MELK]] is attributed to its capacity to disable critical cell-cycle checkpoints and reduce replication stress. Most functional studies have relied on the use of siRNA/shRNA-mediated gene silencing. In the present study, we have explored the biological function of [[MELK]] using [[MELK]]-T1, a novel and selective small-molecule inhibitor. Strikingly, [[MELK]]-T1 triggered a rapid and proteasome-dependent degradation of the [[MELK]] protein. Treatment of MCF-7 (Michigan Cancer Foundation-7) breast adenocarcinoma cells with [[MELK]]-T1 induced the accumulation of stalled replication forks and double-strand breaks that culminated in a replicative senescence phenotype. This phenotype correlated with a rapid and long-lasting ataxia telangiectasia-mutated (ATM) activation and phosphorylation of checkpoint kinase 2 (CHK2). Furthermore, [[MELK]]-T1 induced a strong phosphorylation of p53 (cellular tumour antigen p53), a prolonged up-regulation of p21 (cyclin-dependent kinase inhibitor 1) and a down-regulation of [[FOXM1]] (Forkhead Box M1) target genes. Our data indicate that [[MELK]] is a key stimulator of proliferation by its ability to increase the threshold for DNA-damage tolerance (DDT). Thus, targeting [[MELK]] by the inhibition of both its catalytic activity and its protein stability might sensitize tumours to DNA-damaging agents or radiation therapy by lowering the DNA-damage threshold.
|mesh-terms=* Apoptosis
* Ataxia Telangiectasia Mutated Proteins
* Azepines
* Benzamides
* Breast Neoplasms
* Cell Line, Tumor
* Cell Proliferation
* DNA Damage
* Enzyme Inhibitors
* Female
* Forkhead Box Protein M1
* Forkhead Transcription Factors
* Gene Expression Regulation, Neoplastic
* Humans
* MCF-7 Cells
* Protein-Serine-Threonine Kinases
|keywords=* chemical biology
* deoxyribonucleic acid (DNA) damage response
* maternal embryonic leucine zipper kinase (MELK) kinase
* senescence
* small molecule inhibitors
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643329
}}
{{medline-entry
|title=Increased [[FOXM1]] expression can stimulate DNA repair in normal hepatocytes in vivo but also increases nuclear foci associated with senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25477198
|abstract=[[FOXM1]] is a transcription factor that has been shown to promote cell proliferation in many tissues during early development and high cell turnover tissues in adults. In a number of tumour cell lines, enrichment of [[FOXM1]] has been shown to reduce the DNA damage response (DDR) and induction of senescence by a range of DNA-damaging agents, suggesting a role for the protein in DNA repair. Endogenous [[FOXM1]] is expressed at detectable levels in hepatocytes of mice up to 2 weeks of age, but not in older mice. The aim of this investigation has been to better understand the role of the protein in DDR in normal cells in vivo. Mice with artificially prolonged elevated [[FOXM1]] expression in hepatocytes, were exposed to alkylating diethylnitrosamine. [[FOXM1]]-enriched mice had dampened DDR after treatment with this alkylating agent, which was consistent with observed increase in expression of genes involved in DNA repair. Paradoxically, mice with [[FOXM1]] expression, within weeks after exposure to the DNA-damaging agent, had increased levels of potentially senescent hepatocytes with large nuclear foci, containing 53BP1. Similarly, spontaneous accumulation of these cells seen with normal ageing in mice was increased with [[FOXM1]] enrichment. Despite its known abilities to promote proliferation and DNA repair, and to reduce ROS, enrichment of [[FOXM1]], as with other oncoproteins, may cause increased persistent DNA lesions and/or senescence in normal murine hepatocytes.
|mesh-terms=* Aging
* Animals
* Cell Nucleus
* DNA Repair
* Forkhead Box Protein M1
* Forkhead Transcription Factors
* Hepatocytes
* Mice
* Mice, Inbred C57BL

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522743
}}
{{medline-entry
|title=Cellular senescence and aging: the role of B-[[MYB]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24981831
|abstract=Cellular senescence is a stable cell cycle arrest, caused by insults, such as: telomere erosion, oncogene activation, irradiation, DNA damage, oxidative stress, and viral infection. Extrinsic stimuli such as cell culture stress can also trigger this growth arrest. Senescence is thought to have evolved as an example of antagonistic pleiotropy, as it acts as a tumor suppressor mechanism during the reproductive age, but can promote organismal aging by disrupting tissue renewal, repair, and regeneration later in life. The mechanisms underlying the senescence growth arrest are broadly considered to involve p16(INK4A) -pRB and p53-p21(CIP1/WAF1/SDI1) tumor suppressor pathways; but it is not known what makes the senescence arrest stable and what the critical downstream targets are, as they are likely to be key to the establishment and maintenance of the senescent state. [[MYB]]-related protein B (B-[[MYB]]/[[MYB]]L2), a member of the myeloblastosis family of transcription factors, has recently emerged as a potential candidate for regulating entry into senescence. Here, we review the evidence which indicates that loss of B-[[MYB]] expression has an important role in causing senescence growth arrest. We discuss how B-[[MYB]] acts, as the gatekeeper, to coordinate transit through the cell cycle, in conjunction with the multivulval class B (MuvB) complex and [[FOXM1]] transcription factors. We also evaluate the evidence connecting B-[[MYB]] to the mTOR nutrient signaling pathway and suggest that inhibition of this pathway leading to an extension of healthspan may involve activation of B-[[MYB]].
|mesh-terms=* Aging
* Animals
* Cell Cycle Checkpoints
* Cell Proliferation
* Cellular Senescence
* Humans
* Proto-Oncogene Proteins c-myb
* Signal Transduction
|keywords=* B-MYB
* MuvB
* aging
* cellular senescence
* growth arrest
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331756
}}
{{medline-entry
|title=MiR-506 suppresses proliferation and induces senescence by directly targeting the [[CDK4]]/6-[[FOXM1]] axis in ovarian cancer.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24604117
|abstract=Ovarian carcinoma is the most lethal gynaecological malignancy. Better understanding of the molecular pathogenesis of this disease and effective targeted therapies are needed to improve patient outcomes. MicroRNAs play important roles in cancer progression and have the potential for use as either therapeutic agents or targets. Studies in other cancers have suggested that miR-506 has anti-tumour activity, but its function has yet to be elucidated. We found that deregulation of miR-506 in ovarian carcinoma promotes an aggressive phenotype. Ectopic over-expression of miR-506 in ovarian cancer cells was sufficient to inhibit proliferation and to promote senescence. We also demonstrated that [[CDK4]] and [[CDK6]] are direct targets of miR-506, and that miR-506 can inhibit [[CDK4]]/6-[[FOXM1]] signalling, which is activated in the majority of serous ovarian carcinomas. This newly recognized miR-506-[[CDK4]]/6-[[FOXM1]] axis provides further insight into the pathogenesis of ovarian carcinoma and identifies a potential novel therapeutic agent.
|mesh-terms=* 3' Untranslated Regions
* Binding Sites
* Cell Line, Tumor
* Cell Proliferation
* Cell Survival
* Cellular Senescence
* Cyclin-Dependent Kinase 4
* Cyclin-Dependent Kinase 6
* Female
* Forkhead Box Protein M1
* Forkhead Transcription Factors
* Gene Expression Regulation, Neoplastic
* Genotype
* Humans
* MicroRNAs
* Neoplasms, Cystic, Mucinous, and Serous
* Ovarian Neoplasms
* Phenotype
* Signal Transduction
* Time Factors
* Transfection
|keywords=* FOXM1
* miR-506
* ovarian carcinoma
* proliferation
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144705
}}

FOXL2

2021-05-12T15:38:31Z

OdysseusBot: Новая страница: «Forkhead box protein L2 ==Publications== {{medline-entry |title=Human amniotic mesenchymal stem cells improve ovarian function in natural aging through secretin...»

Forkhead box protein L2

==Publications==

{{medline-entry
|title=Human amniotic mesenchymal stem cells improve ovarian function in natural aging through secreting hepatocyte growth factor and epidermal growth factor.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29523193
|abstract=Although many reports show that various kinds of stem cells have the ability to recover function in premature ovarian aging, few studies have looked at stem cell treatment of natural ovarian aging (NOA). We designed this experimental study to investigate whether human amniotic mesenchymal stem cells (hAMSCs) retain the ability to restore ovarian function, and how hAMSCs work in this process. To build the NOA mouse model, the mice were fed for 12-14 months normally with young fertile female mice as the normal control group (3-5 months old). Hematoxylin and eosin staining permitted follicle counting and showed the ovarian tissue structure. An enzyme-linked immunosorbent assay was used to detect the serum levels of the sex hormones estradiol (E2), anti-mullerian hormone ([[AMH]]), and follicle-stimulating hormone (FSH). The proliferation rate and marker expression level of human ovarian granule cells (hGCs) (ki67, [[AMH]], FSH receptor, [[FOXL2]], and CYP19A1) were measured by flow cytometry (FACS). Cytokines (growth factors) were measured by a protein antibody array methodology. After hepatocyte growth factor ([[HGF]]) and epidermal growth factor ([[EGF]]) were co-cultured with hGCs, proliferation (ki67) and apoptosis (Annexin V) levels were analyzed by FACS. After [[HGF]] and [[EGF]] were injected into the ovaries of natural aging mice, the total follicle numbers and hormone levels were tested. After the hAMSCs were transplanted into the NOA mouse model, the hAMSCs exerted a therapeutic activity on mouse ovarian function by improving the follicle numbers over four stages. In addition, our results showed that hAMSCs significantly promoted the proliferation rate and marker expression level of ovarian granular cells that were from NOA patients. Meanwhile, we found that the secretion level of [[EGF]] and [[HGF]] from hAMSCs was higher than other growth factors. A growth factor combination ([[HGF]] with [[EGF]]) improved the proliferation rate and inhibited the apoptosis rate more powerfully after a co-culture with hGCs, and total follicle numbers and hormone levels were elevated to a normal level after the growth factor combination was injected into the ovaries of the NOA mouse model. These findings provide insight into the notion that hAMSCs play an integral role in resistance to NOA. Furthermore, our present study demonstrates that a growth factor combination derived from hAMSCs plays a central role in inhibiting ovarian aging. Therefore, we suggest that hAMSCs improve ovarian function in natural aging by secreting [[HGF]] and [[EGF]].
|mesh-terms=* Adult
* Amnion
* Animals
* Apoptosis
* Cell Proliferation
* Cells, Cultured
* Epidermal Growth Factor
* Female
* Hepatocyte Growth Factor
* Humans
* Mesenchymal Stem Cell Transplantation
* Mesenchymal Stem Cells
* Mice
* Mice, Inbred C57BL
* Ovary
* Primary Ovarian Insufficiency
|keywords=* EGF
* HGF
* Human amniotic mesenchymal stem cells
* Natural ovarian aging
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845161
}}
{{medline-entry
|title=Different therapeutic effects of cells derived from human amniotic membrane on premature ovarian aging depend on distinct cellular biological characteristics.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28750654
|abstract=Many reports have shown that various kinds of stem cells have the ability to recover premature ovarian aging (POA) function. Transplantation of human amniotic epithelial cells (hAECs) improves ovarian function damaged by chemotherapy in a mice model. Understanding of how to evaluate the distinct effects of adult stem cells in curing POA and how to choose stem cells in clinical application is lacking. To build a different degrees of POA model, mice were administered different doses of cyclophosphamide: light dose (70 mg/kg, 2 weeks), medium dose (70 mg/kg, 1 week; 120 mg/kg, 1 week), and high dose (120 mg/kg, 2 weeks). Enzyme-linked immunosorbent assay detected serum levels of sex hormones, and hematoxylin and eosin staining allowed follicle counting and showed the ovarian tissue structure. DiIC (5)-DS was employed to label human amniotic mesenchymal stem cells (hAMSCs) and hAECs for detecting the cellular retention time in ovaries by a live imaging system. Proliferation of human ovarian granule cells (ki67, [[AMH]], [[FSHR]], [[FOXL2]], and CYP19A1) and immunological rejection of human peripheral blood mononuclear cells (CD4, CD11b, [[CD19]], and CD56) were measured by flow cytometry (fluorescence-activated cell sorting (FACS)). Distinction of cellular biological characteristics between hAECs and hAMSCs was evaluated, such as collagen secretory level (collagen I, II, III, IV, and VI), telomerase activity, pluripotent markers tested by western blot, expression level of immune molecules (HLA-ABC and HLA-DR) analyzed by FACS, and cytokines (growth factors, chemotactic factors, apoptosis factors, and inflammatory factors) measured by a protein antibody array methodology. After hAMSCs and hAECs were transplanted into a different degrees of POA model, hAMSCs exerted better therapeutic activity on mouse ovarian function in the high-dose administration group, promoting the proliferation rate of ovarian granular cells from premature ovarian failure patients, but also provoking immune rejection. Meanwhile, our results showed that the biological characteristics of hAMSCs were superior to hAECs, but not to expression of immune molecules. These results suggest that hAMSCs are a more effective cell type to improve ovarian function than hAECs. Meanwhile, this distinct effect is attributable to cellular biological characteristics of hAMSCs (telomerase activity, expression level of pluripotent markers, cytokine and collagen secretion) that are superior to hAECs, except for immunological rejection. Sufficient consideration of cell properties is warranted to move forward to more effective clinical therapy.
|mesh-terms=* Amnion
* Animals
* Disease Models, Animal
* Epithelial Cells
* Female
* Heterografts
* Humans
* Mice
* Mice, Inbred ICR
* Primary Ovarian Insufficiency
|keywords=* Cellular biological characteristics
* Human amniotic epithelial cells
* Human amniotic mesenchymal stem cells
* Premature ovarian aging
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530953
}}
{{medline-entry
|title=Interactions between genetic variants in [[AMH]] and [[[[AMH]]R2]] may modify age at natural menopause.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23544102
|abstract=The onset of menopause has important implications on women's fertility and health. We previously identified genetic variants in genes involved in initial follicle recruitment as potential modifiers of age at natural menopause. The objective of this study was to extend our previous study, by searching for pairwise interactions between tagging single nucleotide polymorphisms (tSNPs) in the 5 genes previously selected ([[AMH]], [[[[AMH]]R2]], [[BMP15]], [[FOXL2]], GDF9). We performed a cross-sectional study among 3445 women with a natural menopause participating in the Prospect-EPIC study, a population-based prospective cohort study, initiated between 1993 and 1997. Based on the model-based multifactor dimensionality reduction (MB-MDR) test with a permutation-based maxT correction for multiple testing, we found a statistically significant interaction between rs10407022 in [[AMH]] and rs11170547 in [[[[AMH]]R2]] (p = 0.019) associated with age at natural menopause. Rs10407022 did not have a statistically significant main effect. However, rs10407022 is an eQTL SNP that has been shown to influence mRNA expression levels in lymphoblastoid cell lines. This study provides additional insights into the genetic background of age at natural menopause and suggests a role of the [[AMH]] signaling pathway in the onset of natural menopause. However, these results remain suggestive and replication by independent studies is necessary.
|mesh-terms=* Age Factors
* Aging
* Anti-Mullerian Hormone
* Epistasis, Genetic
* Female
* Humans
* Menopause
* Middle Aged
* Ovarian Follicle
* Polymorphism, Single Nucleotide
* Receptors, Peptide
* Receptors, Transforming Growth Factor beta

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609726
}}
{{medline-entry
|title=[[DMRT1]] prevents female reprogramming in the postnatal mammalian testis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21775990
|abstract=Sex in mammals is determined in the fetal gonad by the presence or absence of the Y chromosome gene Sry, which controls whether bipotential precursor cells differentiate into testicular Sertoli cells or ovarian granulosa cells. This pivotal decision in a single gonadal cell type ultimately controls sexual differentiation throughout the body. Sex determination can be viewed as a battle for primacy in the fetal gonad between a male regulatory gene network in which Sry activates Sox9 and a female network involving WNT/β-catenin signalling. In females the primary sex-determining decision is not final: loss of the [[FOXL2]] transcription factor in adult granulosa cells can reprogram granulosa cells into Sertoli cells. Here we show that sexual fate is also surprisingly labile in the testis: loss of the [[DMRT1]] transcription factor in mouse Sertoli cells, even in adults, activates Foxl2 and reprograms Sertoli cells into granulosa cells. In this environment, theca cells form, oestrogen is produced and germ cells appear feminized. Thus Dmrt1 is essential to maintain mammalian testis determination, and competing regulatory networks maintain gonadal sex long after the fetal choice between male and female. Dmrt1 and Foxl2 are conserved throughout vertebrates and Dmrt1-related sexual regulators are conserved throughout metazoans. Antagonism between Dmrt1 and Foxl2 for control of gonadal sex may therefore extend beyond mammals. Reprogramming due to loss of Dmrt1 also may help explain the aetiology of human syndromes linked to [[DMRT1]], including disorders of sexual differentiation and testicular cancer.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Cell Transdifferentiation
* Female
* Feminization
* Forkhead Box Protein L2
* Forkhead Transcription Factors
* Gene Expression Regulation
* Granulosa Cells
* Male
* Mice
* Models, Biological
* Ovary
* RNA, Messenger
* SOX9 Transcription Factor
* Sertoli Cells
* Sex Characteristics
* Sex Determination Processes
* Sex Differentiation
* Testis
* Theca Cells
* Transcription Factors

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150961
}}
{{medline-entry
|title=Genes involved in initial follicle recruitment may be associated with age at menopause.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21193543
|abstract=Timing of menopause is largely influenced by genetic factors. Because menopause occurs when the follicle pool in the ovaries has become exhausted, genes involved in primordial follicle recruitment can be considered as candidate genes for timing of menopause. The aim was to study the association of 23 tagging single nucleotide polymorphisms in five genes [Anti-Müllerian hormone ([[AMH]]), [[AMH]] type II receptor ([[[[AMH]]R2]]), bone morphogenetic protein 15 ([[BMP15]]), forkhead transcription factor L2 ([[FOXL2]]), and growth differentiation factor-9 ([[GDF9]])] involved in recruitment of the primary follicle pool, including the [[[[AMH]]R2]] gene, which has recently been associated with age at menopause. We conducted a cross-sectional association study. We studied a population-based sample of 3616 Dutch women with natural menopause. We measured age at natural menopause. Both studied [[[[AMH]]R2]] tagging single nucleotide polymorphisms (rs2002555 and rs11170547) in the [[[[AMH]]R2]] gene were associated with age at natural menopause in interaction with parity. Parous rs2002555 G/G carriers had menopause 1 yr later compared with A/A carriers (P = 0.01). For rs11170547, each minor allele (T) was associated with a 0.41-yr later onset of menopause in parous women (P = 0.01). Additionally, rs6521896 in [[BMP15]] was associated with later menopause (β = 0.41; P = 0.007). Variants in the [[AMH]], [[FOXL2]], and [[GDF9]] genes were not associated with timing of menopause. The present study confirms an earlier finding that variation in the [[[[AMH]]R2]] gene modifies the relation between parity and age at natural menopause. In combination with the association of [[BMP15]] with menopausal age, we find that there is evidence that genes involved in primary follicle recruitment influence timing of menopause.
|mesh-terms=* Aged
* Aging
* Alleles
* Anti-Mullerian Hormone
* Bone Morphogenetic Protein 15
* Cohort Studies
* Cross-Sectional Studies
* Female
* Forkhead Box Protein L2
* Forkhead Transcription Factors
* Genotype
* Growth Differentiation Factor 9
* Humans
* Menopause
* Middle Aged
* Netherlands
* Ovarian Follicle
* Parity
* Polymorphism, Single Nucleotide
* Postmenopause
* Receptors, Peptide
* Receptors, Transforming Growth Factor beta

|full-text-url=https://sci-hub.do/10.1210/jc.2010-1799
}}

FOXF1

2021-05-12T15:38:28Z

OdysseusBot: Новая страница: «Forkhead box protein F1 (Forkhead-related activator 1) (FREAC-1) (Forkhead-related protein FKHL5) (Forkhead-related transcription factor 1) [FKHL5] [FREAC1] ==Pu...»

Forkhead box protein F1 (Forkhead-related activator 1) (FREAC-1) (Forkhead-related protein FKHL5) (Forkhead-related transcription factor 1) [FKHL5] [FREAC1]

==Publications==

{{medline-entry
|title=Functional CRISPR screen identifies AP1-associated enhancer regulating [[FOXF1]] to modulate oncogene-induced senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30119690
|abstract=Functional characterization of non-coding elements in the human genome is a major genomic challenge and the maturation of genome-editing technologies is revolutionizing our ability to achieve this task. Oncogene-induced senescence, a cellular state of irreversible proliferation arrest that is enforced following excessive oncogenic activity, is a major barrier against cancer transformation; therefore, bypassing oncogene-induced senescence is a critical step in tumorigenesis. Here, we aim at further identification of enhancer elements that are required for the establishment of this state. We first apply genome-wide profiling of enhancer-RNAs (eRNAs) to systematically identify enhancers that are activated upon oncogenic stress. DNA motif analysis of these enhancers indicates AP-1 as a major regulator of the transcriptional program induced by oncogene-induced senescence. We thus constructed a CRISPR-Cas9 sgRNA library designed to target senescence-induced enhancers that are putatively regulated by AP-1 and used it in a functional screen. We identify a critical enhancer that we name Enh and validate that mutating the AP-1 binding site within this element results in oncogene-induced senescence bypass. Furthermore, we identify [[FOXF1]] as the gene regulated by this enhancer and demonstrate that [[FOXF1]] mediates Enh effect on the senescence phenotype. Our study elucidates a novel cascade mediated by AP-1 and [[FOXF1]] that regulates oncogene-induced senescence and further demonstrates the power of CRISPR-based functional genomic screens in deciphering the function of non-coding regulatory elements in the genome.
|mesh-terms=* CRISPR-Cas Systems
* Cellular Senescence
* Enhancer Elements, Genetic
* Forkhead Transcription Factors
* Gene Expression Profiling
* Genetic Testing
* HEK293 Cells
* Humans
* Models, Biological
* Oncogenes
* Transcription Factor AP-1
|keywords=* AP1
* CRISPR
* Enhancers
* FOS
* FOXF1
* Functional screen
* Gene regulation
* JUN
* Oncogene-induced senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097335
}}
{{medline-entry
|title=Co-culturing nucleus pulposus mesenchymal stem cells with notochordal cell-rich nucleus pulposus explants attenuates tumor necrosis factor-α-induced senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29941029
|abstract=Cell therapy for the treatment of intervertebral disc degeneration (IDD) faces serious barriers since tissue-specific adult cells such as nucleus pulposus cells (NPCs) have limited proliferative ability and poor regenerative potential; in addition, it is difficult for exogenous adult stem cells to survive the harsh environment of the degenerated intervertebral disc. Endogenous repair by nucleus pulposus mesenchymal stem cells (NPMSCs) has recently shown promising regenerative potential for the treatment of IDD. Notochordal cells (NCs) and NC-conditioned medium (NCCM) have been proven to possess regenerative ability for the treatment of IDD, but this approach is limited by the isolation and passaging of NCs. Our previous study demonstrated that modified notochordal cell-rich nucleus pulposus (NC-rich NP) has potential for the repair of IDD. However, whether this can protect NPMSCs during IDD has not been evaluated. In the current study, tumor necrosis factor ([[TNF]])-α was used to mimic the inflammatory environment of IDD. Human NPMSCs were cocultured with NC-rich NP explants from healthy rabbit lumbar spine with or without [[TNF]]-α. Cell proliferation and senescence were analyzed to investigate the effect of NC-rich NP explants on [[TNF]]-α-treated NPMSCs. The expression of mRNA encoding proteins related to matrix macromolecules (such as aggrecan, Sox-9, collagen Iα, and collagen IIα), markers related to the nucleus pulposus cell phenotype (including [[CA12]], [[FOXF1]], [[PAX1]], and HIF-1α), and senescence markers (such as p16, p21, and p53), senescence-associated proinflammatory cytokines (IL-6), and extracellular proteases (MMP-13, ADAMTS-5) was assessed. The protein expression of [[CA12]] and collagen II was also evaluated. After a 7-day treatment, the NC-rich NP explant was found to enhance cell proliferation, decrease cellular senescence, promote glycosaminoglycan (GAG), collagen II, and [[CA12]] production, upregulate the expression of extracellular matrix (ECM)-related genes (collagen I, collagen II, [[SOX9]], and ACAN), and enhance the expression of nucleus pulposus cell (NPC) markers (HIF-1α, [[FOXF1]], [[PAX1]], and [[CA12]]). Modified NC-rich NP explants can attenuate [[TNF]]-α-induced degeneration and senescence of NPMSCs in vitro. Our findings provide new insights into the therapeutic potential of NC-rich NP for the treatment of IDD.
|mesh-terms=* Adult
* Cell Proliferation
* Coculture Techniques
* Female
* Humans
* Male
* Mesenchymal Stem Cells
* Middle Aged
* Notochord
* Nucleus Pulposus
* Tumor Necrosis Factor-alpha
|keywords=* Intervertebral disc degeneration
* Notochordal cell-rich nucleus pulposus explants
* Nucleus pulposus mesenchymal stem cells
* Senescence
* TNF-α
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019307
}}

FOXC1

2021-05-12T15:38:24Z

OdysseusBot: Новая страница: «Forkhead box protein C1 (Forkhead-related protein FKHL7) (Forkhead-related transcription factor 3) (FREAC-3) [FKHL7] [FREAC3] ==Publications== {{medline-entry |...»

Forkhead box protein C1 (Forkhead-related protein FKHL7) (Forkhead-related transcription factor 3) (FREAC-3) [FKHL7] [FREAC3]

==Publications==

{{medline-entry
|title=Identification of key genes and transcription factors in aging mesenchymal stem cells by DNA microarray data.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30641220
|abstract=Mesenchymal stem cells ([[MSC]]s) are multipotent cells that can be widely used in stem cell therapy. However, few studies have revealed the potential mechanisms of the changes in aging [[MSC]]. In this study, microarray data GSE35955 was downloaded from the Gene Expression Omnibus database. Then limma package in R was used to filtrate differentially expressed genes (DEGs), Transcription factors ([[TF]]s) were predicted by DCGL package. After predicting [[TF]]s, protein-protein interaction (PPI) network and [[TF]]-mediated transcriptional regulation network were constructed. The functional and pathway enrichment analysis of screened DEGs, hub genes and [[TF]]s were conducted by the DAVID. Totally 156 up-regulated DEGs and 343 down-regulated DEGs were obtained. 6 hub genes ([[CTNNB1]], [[PPP2R1A]], [[FYN]], [[MAPK1]], [[PIK3C2A]] and [[EP300]]) were obtained from PPI network. 11 [[TF]]s (CREB1, [[[[CUX1]]]], [[EGR1]], [[EP300]], [[FOXC1]], [[HSF2]], [[MEF2A]], [[PLAU]], [[SP1]], [[STAT1]] and USF1) for DEGs were predicted and 2 highly scored co-expression relationships ([[EP300]]-[[PPP2R1A]] and [[STAT1]]-[[FOXC1]]) were acquired from the [[TF]]-mediated transcriptional regulation network. The discovery of the hub genes, [[TF]]s and pathways might contribute to the understanding of genetic and molecular functions of aging-related changes in [[MSC]]. Further validation studies on genes and [[TF]]s such as [[CTNNB1]], [[FYN]], [[PPP2R1A]], [[MAPK1]], [[EP300]] and related biological processes and pathways, including adherens junction, DNA damage caused from oxidative stress, attribution of telomere, [[MSC]] differentiation and epigenetic regulation, are urgent for clinical prevention and treatment.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Gene Expression Profiling
* Gene Expression Regulation
* Humans
* Mesenchymal Stem Cells
* Middle Aged
* Mitogen-Activated Protein Kinase 1
* Oligonucleotide Array Sequence Analysis
* Protein Interaction Maps
* Protein Phosphatase 2
* Proto-Oncogene Proteins c-fyn
* Transcription Factors
* beta Catenin
|keywords=* Differentially expressed genes
* Enrichment analysis
* Gene Expression Omnibus
* Hub genes
* Microarray analysis
* Protein-protein interaction network
* Transcriptional regulatory network
|full-text-url=https://sci-hub.do/10.1016/j.gene.2018.12.063
}}
{{medline-entry
|title=[[FOXC1]] maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26912458
|abstract=Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 ([[FOXC1]]) expressed in hair follicle SCs (HFSCs). [[FOXC1]]-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although [[FOXC1]]-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin-mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis.
|mesh-terms=* Adult Stem Cells
* Aging
* Animals
* Cadherins
* Cell Adhesion
* Cell Proliferation
* Forkhead Transcription Factors
* Gene Expression Regulation
* Hair Follicle
* Mice, Knockout
* Mice, Mutant Strains
* Regeneration
* Stem Cell Niche
|keywords=* FOXC1
* aging
* hair follicle
* quiescence
* stem cells
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801248
}}
{{medline-entry
|title=Foxf2: a novel locus for anterior segment dysgenesis adjacent to the Foxc1 gene.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22022403
|abstract=Anterior segment dysgenesis (ASD) is characterised by an abnormal migration of neural crest cells or an aberrant differentiation of the mesenchymal cells during the formation of the eye's anterior segment. These abnormalities result in multiple tissue defects affecting the iris, cornea and drainage structures of the iridocorneal angle including the ciliary body, trabecular meshwork and Schlemm's canal. In some cases, abnormal ASD development leads to glaucoma, which is usually associated with increased intraocular pressure. Haploinsufficiency through mutation or chromosomal deletion of the human [[FOXC1]] transcription factor gene or duplications of the 6p25 region is associated with a spectrum of ocular abnormalities including ASD. However, mapping data and phenotype analysis of human deletions suggests that an additional locus for this condition may be present in the same chromosomal region as [[FOXC1]]. DHPLC screening of ENU mutagenised mouse archival tissue revealed five novel mouse Foxf2 mutations. Re-derivation of one of these (the Foxf2(W174R) mouse lineage) resulted in heterozygote mice that exhibited thinning of the iris stroma, hyperplasia of the trabecular meshwork, small or absent Schlemm's canal and a reduction in the iridocorneal angle. Homozygous E18.5 mice showed absence of ciliary body projections, demonstrating a critical role for Foxf2 in the developing eye. These data provide evidence that the Foxf2 gene, separated from Foxc1 by less than 70 kb of genomic sequence (250 kb in human DNA), may explain human abnormalities in some cases of ASD where [[FOXC1]] has been excluded genetically.
|mesh-terms=* Aging
* Amino Acid Sequence
* Animals
* Base Sequence
* Biological Specimen Banks
* Cornea
* DNA
* Embryo, Mammalian
* Ethylnitrosourea
* Eye Abnormalities
* Forkhead Transcription Factors
* Genetic Loci
* Homozygote
* Iris
* Mice
* Molecular Sequence Data
* Mutation
* Phenotype
* Phylogeny

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192754
}}

FOXA3

2021-05-12T15:38:21Z

OdysseusBot: Новая страница: «Hepatocyte nuclear factor 3-gamma (HNF-3-gamma) (HNF-3G) (Fork head-related protein FKH H3) (Forkhead box protein A3) (Transcription factor 3G) (TCF-3G) [HNF3G] [...»

Hepatocyte nuclear factor 3-gamma (HNF-3-gamma) (HNF-3G) (Fork head-related protein FKH H3) (Forkhead box protein A3) (Transcription factor 3G) (TCF-3G) [HNF3G] [TCF3G]

==Publications==

{{medline-entry
|title=Glucose restriction delays senescence and promotes proliferation of HUVECs via the AMPK/[[SIRT1]]-[[FOXA3]]-Beclin1 pathway.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32768436
|abstract=Caloric restriction (CR) is an important means to delay senescence, and glucose restriction is one of the measures to achieve CR. On the basis of our previous work and bioinformatics analysis, we hypothesized that glucose restriction can up-regulate autophagy, inhibit senescence and promote proliferation via the AMPK/[[SIRT1]]-[[FOXA3]]-Beclin1 pathway in human umbilical vein endothelial cells (HUVECs). We found that compared with 5.5 mmol/L and 25 mmol/L glucose, 2.5 mmol/L glucose restriction significantly reduced senescence, enhanced autophagy, increased migration speed, relieved G /G phase arrest and enhanced proliferation of HUVECs. Furthermore, glucose restriction up-regulated AMPKα1, [[SIRT1]], [[FOXA3]] and Beclin1 expression in HUVECs. Additionally, we demonstrated that AMPKα1 phosphorylated [[FOXA3]] at S170 and S305 in the cytoplasm and promoted [[FOXA3]] nuclear translocation under glucose restriction. [[FOXA3]] in the nucleus was deacetylated by [[SIRT1]] at K214 and K221. Deacetylated [[FOXA3]] specifically bound to 109 C in the Beclin1 transcriptional regulatory region, and significantly enhanced Beclin1 transcription and expression. siRNA knock down of AMPKα1, [[SIRT1]], [[FOXA3]] or Beclin1 expression impaired the glucose restriction-induced inhibition of senescence, enhanced autophagy, increased migration, and induced proliferation of HUVECs. This study confirmed that glucose restriction can enhance autophagy, inhibit senescence, and enhance proliferation of HUVECs through the AMPK/[[SIRT1]]-[[FOXA3]]-Beclin1 pathway.

|keywords=* Beclin1
* Endothelial cells
* FOXA3
* Glucose restriction
* Proliferation
* Senescence
|full-text-url=https://sci-hub.do/10.1016/j.exger.2020.111053
}}

FOXA2

2021-05-12T15:38:19Z

OdysseusBot: Новая страница: «Hepatocyte nuclear factor 3-beta (HNF-3-beta) (HNF-3B) (Forkhead box protein A2) (Transcription factor 3B) (TCF-3B) [HNF3B] [TCF3B] ==Publications== {{medline-e...»

Hepatocyte nuclear factor 3-beta (HNF-3-beta) (HNF-3B) (Forkhead box protein A2) (Transcription factor 3B) (TCF-3B) [HNF3B] [TCF3B]

==Publications==

{{medline-entry
|title=Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons from Adult Common Marmoset Fibroblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28635509
|abstract=The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter life span compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties, including the development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers. In addition, expression of key pluripotency genes (ZFP42, [[PODXL]], [[DNMT3B]], C-[[MYC]], LIN28, [[KLF4]], [[NANOG]], [[SOX2]], and OCT4) was observed. We then tested the neural differentiation capacity and gene expression profiles of Cj-iPSCs and a marmoset embryonic stem cell line (Cj-ESC) after dual-SMAD inhibition. Exposure to CHIR99021 and sonic hedgehog (SHH) for 12 and 16 days, respectively, patterned the cells toward a ventralized midbrain dopaminergic phenotype, confirmed by expression of [[FOXA2]], [[OTX2]], EN-1, and tyrosine hydroxylase. These results demonstrate that common marmoset stem cells will be able to serve as a platform for investigating regenerative medicine approaches targeting the dopaminergic system.
|mesh-terms=* Aging
* Animals
* Callithrix
* Cell Differentiation
* Cell Lineage
* Dopaminergic Neurons
* Fibroblasts
* Gene Expression Regulation
* Induced Pluripotent Stem Cells
* Mesencephalon
|keywords=* Parkinson's disease
* induced pluripotent stem cells
* neural differentiation
* nonhuman primate model
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576272
}}
{{medline-entry
|title=Epigenetic mechanisms of peptidergic regulation of gene expression during aging of human cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25761685
|abstract=Expression levels of genes encoding specific transcription factors and other functionally important proteins vary upon aging of pancreatic and bronchial epithelium cell cultures. The peptides KEDW and AEDL tissue-specifically affect gene expression in pancreatic and bronchial cell cultures, respectively. It is established in this work that the DNA methylation patterns of the [[PDX1]], [[PAX6]], NGN3, [[NKX2-1]], and [[SCGB1A1]] gene promoter regions change upon aging in pancreatic and bronchial cell cultures in correlation with variations in their expression levels. Thus, stable changes in gene expression upon aging of cell cultures could be caused by changes in their promoter methylation patterns. The methylation patterns of the [[PAX4]] gene in pancreatic cells as well as those of the [[FOXA1]], [[SCGB3A2]], and [[SFTPA1]] genes in bronchial cells do not change upon aging and are unaffected by peptides, whereas their expression levels change in both cases. The promoter region of the [[FOXA2]] gene in pancreatic cells contains a small number of methylated CpG sites, their methylation levels being affected by cell culture aging and KEDW, though without any correlation with gene expression levels. The promoter region of the [[FOXA2]] gene is completely unmethylated in bronchial cells irrespective of cell culture age and AEDL action. Changes in promoter methylation might be the cause of age- and peptide-induced variations in expression levels of the [[PDX1]], [[PAX6]], and NGN3 genes in pancreatic cells and [[NKX2-1]] and [[SCGB1A1]] genes in bronchial cells. Expression levels of the [[PAX4]] and [[FOXA2]] genes in pancreatic cells and [[FOXA1]], [[FOXA2]], [[SCGB3A2]], and [[SFTPA1]] genes in bronchial cells seem to be controlled by some other mechanisms.
|mesh-terms=* Aging
* Cell Line
* Cellular Senescence
* DNA Methylation
* Epigenesis, Genetic
* Gene Expression Regulation
* Humans
* Peptides
* Promoter Regions, Genetic

|full-text-url=https://sci-hub.do/10.1134/S0006297915030062
}}

FOXA1

2021-05-12T15:38:16Z

OdysseusBot: Новая страница: «Hepatocyte nuclear factor 3-alpha (HNF-3-alpha) (HNF-3A) (Forkhead box protein A1) (Transcription factor 3A) (TCF-3A) [HNF3A] [TCF3A] ==Publications== {{medline...»

Hepatocyte nuclear factor 3-alpha (HNF-3-alpha) (HNF-3A) (Forkhead box protein A1) (Transcription factor 3A) (TCF-3A) [HNF3A] [TCF3A]

==Publications==

{{medline-entry
|title=Analyses of an epigenetic switch involved in the activation of pioneer factor [[FOXA1]] leading to the prognostic value of estrogen receptor and [[FOXA1]] co-expression in breast cancer.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31562808
|abstract=Forkhead box protein A1 ([i][[FOXA1]][/i]) is a pioneer factor of estrogen receptor α (ER)-chromatin binding and function, yet the role of [i][[FOXA1]][/i] in breast cancer and the underlying molecular mechanisms have not yet been elucidated. To evaluate gene expression alterations during breast carcinogenesis, [i][[FOXA1]][/i] expression was analyzed using the Serial Analysis of Gene Expression Genie suite, a gene expression profiling interactive analysis, and Oncomine analyses. The correlation between methylation and expression was analyzed using the MEXPRESS tool and UCSC Xena browser. Then, the expression and prognostic value of [[FOXA1]] was validated by our own breast cancer samples using RT-PCR. We obtained the following important results. (1) The expression level of [i][[FOXA1]][/i] was significantly higher in breast cancer than normal tissues. (2) ER, PR, HEGR-2, and nodal status were positively correlated with [i][[FOXA1]][/i] expression. (3) Among patients with ER tumors, those with higher [i][[FOXA1]][/i] expression levels had better survival probabilities. (4) The major mutation type in [i][[FOXA1]][/i] in breast cancer samples was missense mutations. (5) [i][[FOXA1]][/i] expression was significantly higher in ER breast tumors than in ER- tumors or normal tissues. Our findings suggest that the aberrant DNA hypomethylation of promoter regions is one mechanism underlying the aberrant expression of [i][[FOXA1]][/i] in ER breast cancer, which might be a potential indicator of favorable prognosis.
|mesh-terms=* Breast Neoplasms
* Down-Regulation
* Epigenesis, Genetic
* Female
* Gene Expression Regulation, Neoplastic
* Hepatocyte Nuclear Factor 3-alpha
* Humans
* Middle Aged
* Prognosis
* RNA, Messenger
* Receptor, ErbB-2
* Receptors, Estrogen
* Receptors, Progesterone
* Transcriptome
* Up-Regulation
|keywords=* FOXA1
* age-related diseases
* aging
* breast cancer
* hormone receptor
* methylation
* prognosis
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6782010
}}
{{medline-entry
|title=The correlation of copy number variations with longevity in a genome-wide association study of Han Chinese.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29883365
|abstract=Copy number variations (CNVs) have been shown to cause numerous diseases, however, their roles in human lifespan remain elusive. In this study, we investigate the association of CNVs with longevity by comparing the Han Chinese genomes of long-lived individuals from 90 to 117 years of age and the middle-aged from 30 to 65. Our data demonstrate that the numbers of CNVs, especially deletions, increase significantly in a direct correlation with longevity. We identify eleven CNVs that strongly associate with longevity; four of them locate in the chromosome bands, 7p11.2, 20q13.33, 19p12 and 8p23.3 and overlap partially with the CNVs identified in long-lived Danish or U.S. populations, while the other seven have not been reported previously. These CNV regions encode nineteen known genes, and some of which have been shown to affect aging-related phenotypes such as the shortening of telomere length ([i]ZNF208[/i]), the risk of cancer ([i][[FOXA1]], [[LAMA5]], ZNF716[/i]), and vascular and immune-related diseases ([i]ARHGEF10, [[[[TOR2A]]]], SH2D3C[/i]). In addition, we found several pathways enriched in long-lived genomes, including [[FOXA1]] and FOXA transcription factor networks involved in regulating aging or age-dependent diseases such as cancer. Thus, our study has identified longevity-associated CNV regions and their affected genes and pathways. Our results suggest that the human genome structures such as CNVs might play an important role in determining a long life in human.
|mesh-terms=* Aged
* Aged, 80 and over
* Asian Continental Ancestry Group
* DNA Copy Number Variations
* Female
* Gene Expression Regulation
* Genome
* Genome-Wide Association Study
* Humans
* Longevity
* Male
|keywords=* Han Chinese
* copy number variation
* genome association study
* long-lived
* longevity
* middle-aged controls
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046244
}}
{{medline-entry
|title=[[FOXA1]] and [[SOX9]] Expression in the Developing Urogenital Sinus of the Tammar Wallaby (Macropus eugenii).
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26406875
|abstract=The mammalian prostate is a compact structure in humans but multi-lobed in mice. In humans and mice, [[FOXA1]] and [[SOX9]] play pivotal roles in prostate morphogenesis, but few other species have been examined. We examined [[FOXA1]] and [[SOX9]] in the marsupial tammar wallaby, Macropus eugenii, which has a segmented prostate more similar to human than to mouse. In males, prostatic budding in the urogenital epithelium (UGE) was initiated by day 24 postpartum (pp), but in the female the UGE remained smooth and had begun forming the marsupial vaginal structures. [[FOXA1]] was upregulated in the male urogenital sinus (UGS) by day 51 pp, whilst in the female UGS [[FOXA1]] remained basal. [[FOXA1]] was localised in the UGE in both sexes between day 20 and 80 pp. [[SOX9]] was upregulated in the male UGS at day 21-30 pp and remained high until day 51-60 pp. [[SOX9]] protein was localised in the distal tips of prostatic buds which were highly proliferative. The persistent upregulation of the transcription factors [[SOX9]] and [[FOXA1]] after the initial peak and fall of androgen levels suggest that in the tammar, as in other mammals, these factors are required to sustain prostate differentiation, development and proliferation as androgen levels return to basal levels.
|mesh-terms=* Aging
* Animals
* Female
* Gene Expression
* Hepatocyte Nuclear Factor 3-alpha
* Humans
* Immunohistochemistry
* Macropodidae
* Male
* Mice
* Polymerase Chain Reaction
* Proliferating Cell Nuclear Antigen
* Prostate
* SOX9 Transcription Factor
* Sex Characteristics
* Urogenital System
* Vagina

|full-text-url=https://sci-hub.do/10.1159/000439499
}}
{{medline-entry
|title=Epigenetic mechanisms of peptidergic regulation of gene expression during aging of human cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25761685
|abstract=Expression levels of genes encoding specific transcription factors and other functionally important proteins vary upon aging of pancreatic and bronchial epithelium cell cultures. The peptides KEDW and AEDL tissue-specifically affect gene expression in pancreatic and bronchial cell cultures, respectively. It is established in this work that the DNA methylation patterns of the [[PDX1]], [[PAX6]], NGN3, [[NKX2-1]], and [[SCGB1A1]] gene promoter regions change upon aging in pancreatic and bronchial cell cultures in correlation with variations in their expression levels. Thus, stable changes in gene expression upon aging of cell cultures could be caused by changes in their promoter methylation patterns. The methylation patterns of the [[PAX4]] gene in pancreatic cells as well as those of the [[FOXA1]], [[SCGB3A2]], and [[SFTPA1]] genes in bronchial cells do not change upon aging and are unaffected by peptides, whereas their expression levels change in both cases. The promoter region of the [[FOXA2]] gene in pancreatic cells contains a small number of methylated CpG sites, their methylation levels being affected by cell culture aging and KEDW, though without any correlation with gene expression levels. The promoter region of the [[FOXA2]] gene is completely unmethylated in bronchial cells irrespective of cell culture age and AEDL action. Changes in promoter methylation might be the cause of age- and peptide-induced variations in expression levels of the [[PDX1]], [[PAX6]], and NGN3 genes in pancreatic cells and [[NKX2-1]] and [[SCGB1A1]] genes in bronchial cells. Expression levels of the [[PAX4]] and [[FOXA2]] genes in pancreatic cells and [[FOXA1]], [[FOXA2]], [[SCGB3A2]], and [[SFTPA1]] genes in bronchial cells seem to be controlled by some other mechanisms.
|mesh-terms=* Aging
* Cell Line
* Cellular Senescence
* DNA Methylation
* Epigenesis, Genetic
* Gene Expression Regulation
* Humans
* Peptides
* Promoter Regions, Genetic

|full-text-url=https://sci-hub.do/10.1134/S0006297915030062
}}
{{medline-entry
|title=Association of levels of fasting glucose and insulin with rare variants at the chromosome 11p11.2-[[MADD]] locus: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24951664
|abstract=Common variation at the 11p11.2 locus, encompassing [[MADD]], [[ACP2]], [[NR1H3]], [[MYBPC3]], and [[SPI1]], has been associated in genome-wide association studies with fasting glucose and insulin (FI). In the Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted Sequencing Study, we sequenced 5 gene regions at 11p11.2 to identify rare, potentially functional variants influencing fasting glucose or FI levels. Sequencing (mean depth, 38×) across 16.1 kb in 3566 individuals without diabetes mellitus identified 653 variants, 79.9% of which were rare (minor allele frequency <1%) and novel. We analyzed rare variants in 5 gene regions with FI or fasting glucose using the sequence kernel association test. At [[NR1H3]], 53 rare variants were jointly associated with FI (P=2.73×10(-3)); of these, 7 were predicted to have regulatory function and showed association with FI (P=1.28×10(-3)). Conditioning on 2 previously associated variants at [[MADD]] (rs7944584, rs10838687) did not attenuate this association, suggesting that there are >2 independent signals at 11p11.2. One predicted regulatory variant, chr11:47227430 (hg18; minor allele frequency=0.00068), contributed 20.6% to the overall sequence kernel association test score at [[NR1H3]], lies in intron 2 of [[NR1H3]], and is a predicted binding site for forkhead box A1 ([[FOXA1]]), a transcription factor associated with insulin regulation. In human HepG2 hepatoma cells, the rare chr11:47227430 A allele disrupted [[FOXA1]] binding and reduced [[FOXA1]]-dependent transcriptional activity. Sequencing at 11p11.2-[[NR1H3]] identified rare variation associated with FI. One variant, chr11:47227430, seems to be functional, with the rare A allele reducing transcription factor [[FOXA1]] binding and [[FOXA1]]-dependent transcriptional activity.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Blood Glucose
* Chromosomes, Human, Pair 11
* Cohort Studies
* Death Domain Receptor Signaling Adaptor Proteins
* Diabetes Mellitus, Type 2
* Fasting
* Female
* Gene Frequency
* Genetic Variation
* Genome-Wide Association Study
* Genomics
* Guanine Nucleotide Exchange Factors
* Heart Diseases
* Humans
* Insulin
* Male
* Middle Aged
* Polymorphism, Single Nucleotide
* Sequence Analysis, DNA
|keywords=* genetic epidemiology
* glucose
* human genetics
* insulin
* molecular genetics
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066205
}}

FOSL2

2021-05-12T15:38:13Z

OdysseusBot: Новая страница: «Fos-related antigen 2 (FRA-2) [FRA2] ==Publications== {{medline-entry |title=LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1α-FOXO4-p21...»

Fos-related antigen 2 (FRA-2) [FRA2]

==Publications==

{{medline-entry
|title=LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1α-[[FOXO4]]-p21-dependent signaling axis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32149459
|abstract=The long noncoding RNA GUARDIN functions to protect genome stability. Inhibiting GUARDIN expression can alter cell fate decisions toward senescence or apoptosis, but the underlying molecular signals are unknown. Here, we show that GUARDIN is an essential component of a transcriptional repressor complex involving LRP130 and PGC1α. GUARDIN acts as a scaffold to stabilize LRP130/PGC1α heterodimers and their occupancy at the [[FOXO4]] promotor. Destabilizing this complex by silencing of GUARDIN, LRP130, or PGC1α leads to increased expression of [[FOXO4]] and upregulation of its target gene p21, thereby driving cells into senescence. We also found that GUARDIN expression was induced by rapamycin, an agent that suppresses cell senescence. [[FOS]]-like antigen 2 ([[[[FOS]]L2]]) acts as a transcriptional repressor of GUARDIN, and lower [[[[FOS]]L2]] levels in response to rapamycin correlate with increased levels of GUARDIN. Together, these results demonstrate that GUARDIN inhibits p21-dependent senescence through a LRP130-PGC1α-[[FOXO4]] signaling axis, and moreover, GUARDIN contributes to the anti-aging activities of rapamycin.

|keywords=*
GUARDIN

* LRP130-PGC1α
* cellular senescence
* lncRNAs
* p21
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132339
}}

FNTA

2021-05-12T15:38:08Z

OdysseusBot: Новая страница: «Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha (EC 2.5.1.58) (EC 2.5.1.59) (CAAX farnesyltransferase subunit alpha) (FTase-alpha) (Ras...»

Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha (EC 2.5.1.58) (EC 2.5.1.59) (CAAX farnesyltransferase subunit alpha) (FTase-alpha) (Ras proteins prenyltransferase subunit alpha) (Type I protein geranyl-geranyltransferase subunit alpha) (GGTase-I-alpha)

==Publications==

{{medline-entry
|title=The Hip Morphology Changes with Ageing in Asian Population.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30363710
|abstract=This study aims to determine the changing in hip anatomy parameters with age and reveals the reason for the extorsion of lower extremity in the aged. Retrospective study. One hundred and forty patients who had received imaging check of the femur and acetabulum between October 2013 and October 2016 were included in this study. The femoral neck torsion angle ([[FNTA]]), neck-shaft angle (NSA), and acetabular anteversion angle (AVA) were measured by an experienced orthopedic surgeon. All the patients' demographic and physical characteristics including age, sex, body laterality, height, and weight were recorded. The Student [i]t[/i]-test, two-way ANOVA, Pearson correlation, and multiple linear regression were used for the statistical analysis. The mean age for male and female was 45.01±15.38 and 49.30±17.63 years, respectively. Outcomes revealed that the NSA on the right side of the body, 133.46±4.46° in male and 134.36±4.71° in female, was statistically higher than the left side. Female [[FNTA]] had significantly higher values than male ([i]P[/i]<0.01). Two-way ANOVA reveals that [[FNTA]] and AVA were correlated with age (P<0.05) but not weight, height, or BMI. NSA was correlated with age, weight, and BMI (P<0.05) but not height. Multiple linear regression analysis showed that only age made an independent contribution to NSA. The NSA and [[FNTA]] of Asian population may have an obvious decrease whereas AVA increases with ageing, which reveals the reason for the extorsion of lower extremity with elderly. During hip-related surgery in elderly patients, more attention should be paid to these lower extremity anatomic changes.
|mesh-terms=* Acetabulum
* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Asian Continental Ancestry Group
* Female
* Femur Head
* Femur Neck
* Hip Joint
* Humans
* Male
* Middle Aged
* Regression Analysis
* Retrospective Studies
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180959
}}

FNDC5

2021-05-12T15:38:05Z

OdysseusBot: Новая страница: «Fibronectin type III domain-containing protein 5 precursor (Fibronectin type III repeat-containing protein 2) [Contains: Irisin] [FRCP2] ==Publications== {{medl...»

Fibronectin type III domain-containing protein 5 precursor (Fibronectin type III repeat-containing protein 2) [Contains: Irisin] [FRCP2]

==Publications==

{{medline-entry
|title=Irisin Correlates Positively With BMD in a Cohort of Older Adult Patients and Downregulates the Senescent Marker p21 in Osteoblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33053231
|abstract=Irisin is a myokine produced by skeletal muscle during exercise in both mice and humans. We previously showed that irisin treatment ameliorates immobility-induced osteoporosis and muscular atrophy in mice. Data in humans showed a positive association between irisin and bone mineral density (BMD) in athletes and a population of healthy children. However, the role of this myokine regarding the state of muscle and bone in the same population remained to be determined. For this purpose, 62 patients (age 68.71 ± 12.31 years) undergoing total hip or knee replacement were recruited. Our results showed that irisin serum levels negatively correlated with age (R = -0.515; p = .000018) and positively correlated with femoral BMD (R = 0.619; p = .001) and vertebral BMD (R = 0.201; p = .0001). Irisin was also positively associated with Fndc5 mRNA in muscle biopsies (R = 0.248; p = .016), as well as with Osteocalcin (Ocn) mRNA in bone biopsies (R = 0.708; p = .006). In skeletal muscle, [[FNDC5]] positive fibers positively correlate with BMD of total femur (R = 0.765; p = .0014) and BMD of femoral neck (R = 0.575; p = .031), Interestingly, by analyzing patients divided by their T-score, we found lower irisin levels (p = .0011) in patients with osteopenia/osteoporosis (OP) compared to healthy controls matched for age and sex. By analyzing the senescence marker p21, we found a significant increase of its mRNA expression in the bone biopsies of OP patients compared to control ones. Therefore, we investigated in vitro whether rec-irisin had a direct effect on this senescence marker, showing that p21 mRNA expression was significantly downregulated in osteoblasts by the treatment with irisin. Overall, these results indicate that higher irisin levels are associated with a lower rate of age-related osteoporosis and that irisin could be effective in delaying the osteoblast aging process, suggesting a potential senolytic action of this myokine. © 2020 American Society for Bone and Mineral Research (ASBMR).

|keywords=* BONE-MUSCLE INTERACTIONS
* IRISIN
* OSTEOPOROSIS
* SARCOPENIA
* SENESCENCE
|full-text-url=https://sci-hub.do/10.1002/jbmr.4192
}}
{{medline-entry
|title=Muscle-dependent regulation of adipose tissue function in long-lived growth hormone-mutant mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32464603
|abstract=Altered adipose tissue may contribute to the longevity of Snell dwarf and growth hormone receptor ([[GHR]]) knock-out mice. We report here that white (WAT) and brown (BAT) fat have elevated [[UCP1]] in both kinds of mice, and that adipocytes in WAT depots turn beige/brown. These imply increased thermogenesis and are expected to lead to improved glucose control. Both kinds of long-lived mice show lower levels of inflammatory M1 macrophages and higher levels of anti-inflammatory M2 macrophages in BAT and WAT, with correspondingly lower levels of TNFα, IL-6, and MCP1. Experiments with mice with tissue-specific disruption of [[GHR]] showed that these adipocyte and macrophage changes were not due to hepatic [[IGF1]] production nor to direct GH effects on adipocytes, but instead reflect GH effects on muscle. Muscles deprived of GH signals, either globally (GKO) or in muscle only (MKO), produce higher levels of circulating irisin and its precursor [[FNDC5]]. The data thus suggest that the changes in adipose tissue differentiation and inflammatory status seen in long-lived mutant mice reflect interruption of GH-dependent irisin inhibition, with consequential effects on metabolism and thermogenesis.

|keywords=* adipose tissue
* aging
* growth hormone
* inflammation
* uncoupling protein 1 (UCP1)
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288969
}}
{{medline-entry
|title=[Investigation of signal molecules in saliva: prospects of application for diagnostics of myocardial infarction and the aging rate of different age people.]
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31512422
|abstract=Among the diseases of the cardiovascular system in elderly people, ischemic heart disease and myocardial infarction (MI) occupy the first place in the structure of mortality. One of the main causes of disability and death from MI is late diagnosis. In this regard, the search for new, highly informative and non-invasive methods for diagnosing MI is an important task of molecular gerontology. An enzyme immunoassay showed that the concentration of [[TNF]]-α, IL-8 cytokines and p16 aging marker in saliva in elderly people without cardiovascular pathologies ([[CP]]) increases in 2,1-4,8 times as compared with middle-aged people. At the same time, in elderly people without [[CP]] the concentration in the saliva of the hormone irisin ([[FNDC5]]) decreases by 1,8 times as compared with middle-aged people. In middle-aged patients with MI the concentration of IL-8, [[TNF]]-α, [[MMP8]], [[MMP9]] in saliva increases 4,3-15,3 times, and [[FNDC5]] decreases 1,8 times compared with those parameters without [[CP]] in this age group. In elderly people with MI the concentration of IL-8, [[TNF]]-α, [[MMP8]] and [[MMP9]] in saliva increases 4,3-7,1 times as compared with elderly people without [[CP]]. Thus, the study of the concentration of signaling molecules IL-8, [[TNF]]-α, [[MMP8]], [[MMP9]] in saliva can be used as a non-invasive method for diagnosing MI in people of middle and elderly age. To assess the rate of aging of the organism in middle-aged and elderly people without [[CP]], a study of the concentration of p16 and [[FNDC5]] molecules in saliva is recommended.
|mesh-terms=* Aged
* Aging
* Biomarkers
* Cytokines
* Humans
* Middle Aged
* Myocardial Infarction
* Saliva
* Tumor Necrosis Factor-alpha
|keywords=* aging
* diagnosis
* myocardial infarction
* saliva
* signaling molecules

}}
{{medline-entry
|title=Mechanistic complexities of bone loss in Alzheimer's disease: a review.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31184223
|abstract=: Alzheimer's disease (AD), the primary cause of dementia in the elderly, is one of the leading age-related neurodegenerative diseases worldwide. While AD is notorious for destroying memory and cognition, dementia patients also experience greater incidence of bone loss and skeletal fracture than age-matched neurotypical individuals, greatly impacting their quality of life. Despite the significance of this comorbidity, there is no solid understanding of the mechanisms driving early bone loss in AD. Here, we review studies that have evaluated many of the obvious risk factors shared by dementia and osteoporosis, and illuminate emerging work investigating covert pathophysiological mechanisms shared between the disorders that may have potential as new risk biomarkers or therapeutic targets in AD. : Skeletal deficits emerge very early in clinical Alzheimer's progression, and cannot be explained by coincident factors such as aging, female sex, mobility status, falls, or genetics. While research in this area is still in its infancy, studies implicate several potential mechanisms in disrupting skeletal homeostasis that include direct effects of amyloid-beta pathology on bone cells, neurofibrillary tau-induced damage to neural centers regulating skeletal remodeling, and/or systemic Wnt/Beta-catenin signaling deficits. Data from an increasing number of studies substantiate a role for the newly discovered "exercise hormone" irisin and its protein precursor [[FNDC5]] in bone loss and AD-associated neurodegeneration. We conclude that the current status of research on bone loss in AD is insufficient and merits critical attention because this work could uncover novel diagnostic and therapeutic opportunities desperately needed to address AD.

|keywords=* Aging
* Alzheimer’s
* bone density
* dementia
* osteoporosis
|full-text-url=https://sci-hub.do/10.1080/03008207.2019.1624734
}}
{{medline-entry
|title=Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30071357
|abstract=Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people at risk for increased vulnerability, disease, injury, and mortality. However, complementary molecular frailty biomarkers or ideally biomarker panels have not yet been identified. We conducted a systematic search to identify biomarker candidates for a frailty biomarker panel. Gene expression databases were searched (http://genomics.senescence.info/genes including GenAge, AnAge, LongevityMap, CellAge, DrugAge, Digital Aging Atlas) to identify genes regulated in aging, longevity, and age-related diseases with a focus on secreted factors or molecules detectable in body fluids as potential frailty biomarkers. Factors broadly expressed, related to several "hallmark of aging" pathways as well as used or predicted as biomarkers in other disease settings, particularly age-related pathologies, were identified. This set of biomarkers was further expanded according to the expertise and experience of the authors. In the next step, biomarkers were assigned to six "hallmark of aging" pathways, namely (1) inflammation, (2) mitochondria and apoptosis, (3) calcium homeostasis, (4) fibrosis, (5) NMJ (neuromuscular junction) and neurons, (6) cytoskeleton and hormones, or (7) other principles and an extensive literature search was performed for each candidate to explore their potential and priority as frailty biomarkers. A total of 44 markers were evaluated in the seven categories listed above, and 19 were awarded a high priority score, 22 identified as medium priority and three were low priority. In each category high and medium priority markers were identified. Biomarker panels for frailty would be of high value and better than single markers. Based on our search we would propose a core panel of frailty biomarkers consisting of (1) [[CXCL10]] (C-X-C motif chemokine ligand 10), IL-6 (interleukin 6), [[CX3CL1]] (C-X3-C motif chemokine ligand 1), (2) [[GDF15]] (growth differentiation factor 15), [[FNDC5]] (fibronectin type III domain containing 5), vimentin (VIM), (3) regucalcin (RGN/SMP30), calreticulin, (4) [[PLAU]] (plasminogen activator, urokinase), [[AGT]] (angiotensinogen), (5) [[BDNF]] (brain derived neurotrophic factor), progranulin (PGRN), (6) α-klotho (KL), [[FGF23]] (fibroblast growth factor 23), [[FGF21]], leptin (LEP), (7) miRNA (micro Ribonucleic acid) panel (to be further defined), [[AHCY]] (adenosylhomocysteinase) and [[KRT18]] (keratin 18). An expanded panel would also include (1) pentraxin (PTX3), sVCAM/ICAM (soluble vascular cell adhesion molecule 1/Intercellular adhesion molecule 1), defensin α, (2) [[APP]] (amyloid beta precursor protein), LDH (lactate dehydrogenase), (3) [[S100B]] (S100 calcium binding protein B), (4) TGFβ (transforming growth factor beta), PAI-1 (plasminogen activator inhibitor 1), [[TGM2]] (transglutaminase 2), (5) sRAGE (soluble receptor for advanced glycosylation end products), [[HMGB1]] (high mobility group box 1), C3/C1Q (complement factor 3/1Q), ST2 (Interleukin 1 receptor like 1), agrin (AGRN), (6) IGF-1 (insulin-like growth factor 1), resistin (RETN), adiponectin (ADIPOQ), ghrelin (GHRL), growth hormone (GH), (7) microparticle panel (to be further defined), GpnmB (glycoprotein nonmetastatic melanoma protein B) and lactoferrin (LTF). We believe that these predicted panels need to be experimentally explored in animal models and frail cohorts in order to ascertain their diagnostic, prognostic and therapeutic potential.
|mesh-terms=* Aged
* Aging
* Amyloid beta-Peptides
* Amyloid beta-Protein Precursor
* Animals
* Apoptosis
* Biomarkers
* Fibronectins
* Frailty
* Genetic Association Studies
* Growth Differentiation Factor 15
* Humans
* Insulin-Like Growth Factor I
* Interleukin-1 Receptor-Like 1 Protein
* Membrane Glycoproteins
* MicroRNAs
* Signal Transduction
|keywords=* Age-related diseases
* Biomarker panel
* Frailty
* Hallmark of aging pathways
|full-text-url=https://sci-hub.do/10.1016/j.arr.2018.07.004
}}
{{medline-entry
|title=Exercise Training Protects Against Aging-Induced Cognitive Dysfunction via Activation of the Hippocampal [[PGC]]-1α/[[FNDC5]]/[[BDNF]] Pathway.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29971668
|abstract=This study aimed to determine the effect of exercise training on cognitive functioning, and hippocampal [[PGC]]-1α, [[FNDC5]], [[BDNF]], and other cognition-related gene and protein expression in rats. Rats were divided into 4 groups based on age [3 months (young) vs. 20 months (aged)] and training status (control vs. exercise training). The rats that exercised voluntarily performed exercise training for 90 days, and then all the rats underwent several methods of behavioral assessment. Locomotor activity and spatial memory were lower but anxiety scores were higher in the aged control rats, than in the young control, young exercised, and aged exercised rats (P < 0.05). Hippocampal [[BDNF]], [[FNDC5]], [[PGC]]-1α, mTOR, [[ARC]], cF-OS, ERK, SIRT, and FOXO expressions were lower, but NF-κB expressions were higher in the aged control rats than in the young control, young exercised, and aged exercised rats (P < 0.05). Similarly, hippocampal [[BDNF]] and [[FNDC5]] protein expression were lower in the aged control rats than in the young control, young exercised, and aged exercised rats (P < 0.05). These findings show that aging-induced cognitive dysfunction is associated with a decrease in hippocampal expression of [[PGC]]-1α, [[FNDC5]], and [[BDNF]], and that exercise training might improve cognitive functioning via activation of these genes and proteins.
|mesh-terms=* Accessory Atrioventricular Bundle
* Aging
* Animals
* Anxiety
* Body Weight
* Brain-Derived Neurotrophic Factor
* Cognitive Dysfunction
* Exploratory Behavior
* Female
* Fibronectins
* Hippocampus
* Locomotion
* Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
* Physical Conditioning, Animal
* Rats
* Signal Transduction
* Spatial Memory
|keywords=* Aging
* BDNF
* Cognition
* Exercise
* FNDC5
* Irisin
|full-text-url=https://sci-hub.do/10.1007/s12017-018-8500-3
}}
{{medline-entry
|title=Epistasis, physical capacity-related genes and exceptional longevity: [[FNDC5]] gene interactions with candidate genes FOXOA3 and [[APOE]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29143599
|abstract=Forkhead box O3A (FOXOA3) and apolipoprotein E ([[APOE]]) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of 'modifier genes', may contribute to explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population. A total of 1565 individuals were studied, subdivided into 822 middle-aged controls and 743 centenarians. We found a FOXOA3 rs2802292 T-allele-dependent association of fibronectin type III domain-containing 5 (FDNC5) rs16835198 with EL: the frequency of carriers of the FOXOA3 rs2802292 T-allele among individuals with the rs16835198 GG genotype was significantly higher in cases than in controls (P < 0.05). On the other hand, among non-carriers of the [[APOE]] 'risk' ε4-allele, the frequency of the FDNC5 rs16835198 G-allele was higher in cases than in controls (48.4% vs. 43.6%, P < 0.05). Among carriers of the 'non-risk' [[APOE]] ε2-allele, the frequency of the rs16835198 G-allele was higher in cases than in controls (49% vs. 37.3%, P < 0.05). The association of FDNC5 rs16835198 with EL seems to depend on the presence of the FOXOA3 rs2802292 T-allele and we report a novel association between [[FNDC5]] rs16835198 stratified by the presence of the [[APOE]] ε2/ε4-allele and EL. More research on 'gene*gene' and 'gene*environment' effects is needed in the field of EL.
|mesh-terms=* Adult
* Apolipoproteins E
* Epistasis, Genetic
* Exercise
* Female
* Fibronectins
* Forkhead Box Protein O3
* Gene Frequency
* Genotype
* Humans
* Longevity
* Male
* Middle Aged
* Polymorphism, Single Nucleotide
* Young Adult
|keywords=* APOE
* Ageing
* Centenarians
* Exceptional longevity
* FNDC5
* FOXO3A
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688477
}}
{{medline-entry
|title=Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28108329
|abstract=Exercise is known to have numerous beneficial effects. Recent studies indicate that exercise improves mitochondrial energetics not only in skeletal muscle but also in other tissues. While exercise elicits positive effects on memory, neurogenesis, and synaptic plasticity, the effects of exercise on brain mitochondrial energetics remain relatively unknown. Herein, we studied the effects of exercise training in old and young mice on brain mitochondrial energetics, in comparison to known effects on peripheral tissues that utilize fatty acid oxidation. Exercise improved the capacity for muscle and liver to oxidize palmitate in old mice, but not young mice. In the brain, exercise increased rates of respiration and reactive oxygen species (ROS) production in the old group only while utilizing complex I substrates, effects that were not seen in the young group. Coupled complex I to III enzymatic activity was significantly increased in old trained versus untrained mice with no effect on coupled II to III enzymatic activity. Mitochondrial protein content and markers of mitochondrial biogenesis (PGC-1α and TFAM) were not affected by exercise training in the brain, in contrast to the skeletal muscle of old mice. Brain levels of the autophagy marker LC3-II and protein levels of other signaling proteins that regulate metabolism or transport (BDNF, HSP60, phosphorylated mTOR, [[FNDC5]], SIRT3) were not significantly altered. Old exercised mice showed a significant increase in DRP1 protein levels in the brain without changes in phosphorylation, while [[MFN2]] and [[OPA1]] protein levels were unchanged. Our results suggest that exercise training in old mice can improve brain mitochondrial function through effects on electron transport chain function and mitochondrial dynamics without increasing mitochondrial biogenesis.
|mesh-terms=* Aging
* Animals
* Cerebellar Cortex
* Dynamins
* Electron Transport Complex I
* Male
* Mice
* Mice, Inbred C57BL
* Mitochondria, Muscle
* Mitochondrial Dynamics
* Mitochondrial Proteins
* Organelle Biogenesis
* Physical Conditioning, Animal
* Reactive Oxygen Species
* Signal Transduction
|keywords=* Brain
* Complex I
* Cortex
* DRP1
* Exercise
* Mitochondria
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346470
}}
{{medline-entry
|title=Irisin-encoding gene ([[FNDC5]]) variant is associated with changes in blood pressure and lipid profile in type 2 diabetic women but not in men.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26024756
|abstract=Irisin has recently been described as a novel myokine, which reduces visceral obesity and improves glucose metabolism in mice. Thus, polymorphisms in the gene encoding irisin, fibronectin type III domain containing 5 ([[FNDC5]]), may be associated with type 2 diabetes mellitus (T2DM) and related disorders. However, to date, no study has investigated the association between [[FNDC5]] polymorphisms and susceptibility to T2DM. To investigate the association of [[FNDC5]] rs3480 (A/G) and rs1746661 (G/T) polymorphisms, alone or in combination, with T2DM and its clinical features. We analyzed 1006 T2DM patients and 434 nondiabetic subjects. Polymorphisms were genotyped by real-time PCR using TaqMan MGB probes. Haplotypes constructed from the combination of rs1746661 and rs3480 polymorphisms were inferred using the Phase 2.1 program. Genotype, allele and haplotype frequencies of rs1746661 and rs3480 polymorphisms did not differ significantly between nondiabetic subjects and T2DM patients. Women with T2DM carrying the G allele of rs3480 showed increased HbA1c levels compared with A/A carriers, adjusted for age. The T allele of rs1746661 was associated with increased systolic blood pressure, total cholesterol and LDL-cholesterol and decreased HDL-cholesterol in women with T2DM, adjusted for covariates. Moreover, prevalence of hypercholesterolemia was higher in women carrying the T allele of rs1746661 than in G/G carriers (72.4% vs. 58.7%, OR=2.010, 95% CI=1.210-3.390), but it was not significantly different in men. These results indicate that, although not associated with T2DM, the G allele of rs3480 appears to be associated with increased HbA1c, while the T allele of rs1746661 appears to be associated with higher systolic blood pressure and dyslipidemia in women with T2DM.
|mesh-terms=* Aging
* Blood Pressure
* Cholesterol
* Diabetes Mellitus, Type 2
* Female
* Fibronectins
* Gene Frequency
* Genotype
* Glycated Hemoglobin A
* Heterozygote
* Humans
* Linkage Disequilibrium
* Lipids
* Male
* Middle Aged
* Polymorphism, Genetic
* Sex Characteristics
|keywords=* Blood pressure
* Dyslipidemia
* FNDC5 gene
* Irisin
* Type 2 diabetes mellitus
|full-text-url=https://sci-hub.do/10.1016/j.metabol.2015.05.005
}}
{{medline-entry
|title=[[FNDC5]] (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25427998
|abstract=Irisin might play an important role in reducing the risk of obesity, insulin resistance, or several related diseases, and high irisin levels may contribute to successful aging. Thus, the irisin precursor ([[FNDC5]]) gene is a candidate to influence exceptional longevity (EL), i.e., being a centenarian. It has been recently shown that two single-nucleotide polymorphisms (SNPs) in the [[FNDC5]] gene, rs16835198 and rs726344, are associated with in vivo insulin sensitivity in adults. We determined luciferase gene reporter activity in the two above-mentioned SNPs and studied genotype distributions among centenarians (n = 175, 144 women) and healthy controls (n = 347, 142 women) from Spain. We also studied an Italian [79 healthy centenarians (40 women) and 316 healthy controls (156 women)] and a Japanese cohort [742 centenarians (623 women) and 499 healthy controls (356 women)]. The rs726344 SNP had functional significance, as shown by differences in luciferase activity between the constructs of this SNP (all P ≤ 0.05), with the variant A-allele having higher luciferase activity compared with the G-allele (P = 0.04). For the rs16835198 SNP, the variant T-allele tended to show higher luciferase activity compared with the G-allele (P = 0.07). However, we found no differences between genotype/allele frequencies of the two SNPs in centenarians versus controls in any cohort, and no significant association (using logistic regression adjusted by sex) between the two SNPs and EL. Further research is needed with different cohorts as well as with additional variants in the [[FNDC5]] gene or in other genes involved in irisin signaling.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Cohort Studies
* Confidence Intervals
* Female
* Fibronectins
* Gene Frequency
* Genotype
* Humans
* Italy
* Japan
* Logistic Models
* Longevity
* Male
* Middle Aged
* Odds Ratio
* Polymorphism, Single Nucleotide
* Reference Values
* Spain
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245403
}}

FN1

2021-05-12T15:38:02Z

OdysseusBot: Новая страница: «Fibronectin precursor (FN) (Cold-insoluble globulin) (CIG) [Contains: Anastellin; Ugl-Y1; Ugl-Y2; Ugl-Y3] [FN] ==Publications== {{medline-entry |title=Systems b...»

Fibronectin precursor (FN) (Cold-insoluble globulin) (CIG) [Contains: Anastellin; Ugl-Y1; Ugl-Y2; Ugl-Y3] [FN]

==Publications==

{{medline-entry
|title=Systems biology and network pharmacology of frailty reveal novel epigenetic targets and mechanisms.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31332237
|abstract=Frailty is an age-associated condition, characterized by an inappropriate response to stress that results in a higher frequency of adverse outcomes (e.g., mortality, institutionalization and disability). Some light has been shed over its genetic background, but this is still a matter of debate. In the present study, we used network biology to analyze the interactome of frailty-related genes at different levels to relate them with pathways, clinical deficits and drugs with potential therapeutic implications. Significant pathways involved in frailty: apoptosis, proteolysis, muscle proliferation, and inflammation; genes as [[FN1]], [[APP]], [[CREBBP]], [[EGFR]] playing a role as hubs and bottlenecks in the interactome network and epigenetic factors as HIST1H3 cluster and miR200 family were also involved. When connecting clinical deficits and genes, we identified five clusters that give insights into the biology of frailty: cancer, glucocorticoid receptor, [[TNF]]-α, myostatin, angiotensin converter enzyme, ApoE, interleukine-12 and -18. Finally, when performing network pharmacology analysis of the target nodes, some compounds were identified as potentially therapeutic (e.g., epigallocatechin gallate and antirheumatic agents); while some other substances appeared to be toxicants that may be involved in the development of this condition.
|mesh-terms=* Aging
* Apoptosis
* Cell Proliferation
* Epigenesis, Genetic
* Frailty
* Genes
* Humans
* Muscle, Smooth
* Pharmacology
* Proteolysis
* Signal Transduction
* Systems Biology

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646318
}}
{{medline-entry
|title=Effects of Fibronectin 1 on Cell Proliferation, Senescence and Apoptosis of Human Glioma Cells Through the PI3K/AKT Signaling Pathway.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30048971
|abstract=The current study aimed to investigate the role by which fibronectin 1 ([[FN1]]) influences the cell cycle, senescence and apoptosis in human glioma cells through the PI3K/ AKT signaling pathway. Differentially expressed genes (DEGs) were identified based on gene expression data (GSE12657, GSE15824 and GSE45921 datasets) and probe annotation files from Gene Expression Omnibus. The DEGs were identified in connection with gene ontology (GO) enrichment analysis and with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The positive expression of the [[FN1]] protein was detected by immunohistochemistry. The glioma cell lines U251 and T98G were selected and assigned into blank, negative control (NC) and siRNA-[[FN1]] groups. A dual luciferase reporter gene assay was used to investigate the effects of [[FN1]] on transcriptional activity through the PI3K/AKT signaling pathway. An MTT assay was applied for the detection of cell proliferation, while flow cytometry was employed for cell cycle stage and cellular apoptosis detection. β-galactosidase staining was utilized to detect cellular senescence, a scratch test was applied to evaluate cell migration, and a transwell assay was used to analyze cell invasion. Western blotting and qRT-PCR methods were used to detect the protein and mRNA expression levels, respectively, of the [[FN1]] gene and the related genes in the PI3K/AKT pathway (PI3K, AKT and PTEN), the cell cycle (pRb, [[CDK4]] and Cyclin D1) and cell senescence (p16 and p21) among the collected tissues and cells. GSE12657 profiling revealed [[FN1]] to be the most upregulated gene in glioma. Regarding the GSE12657 and GSE15824 datasets, [[FN1]] gene expression was higher in glioma tissues than in normal tissues. GO enrichment analysis and KEGG pathway enrichment analysis indicated that [[FN1]] is involved in the synthesis of extracellular matrix (ECM) components and the PI3K/AKT signaling pathway. Verification was provided, indicating the role played by the [[FN1]] gene in the regulation of the PI3K/AKT signaling pathway, as silencing the [[FN1]] gene was found to inhibit cell proliferation, promote cell apoptosis and senescence, and reduce migration and invasion through the down-regulation of [[FN1]] gene expression and disruption of the PI3K-AKT signaling pathway. The findings of this study provide evidence highlighting the prominent role played by [[FN1]] in stimulating glioma growth, invasion, and survival through the activation of the PI3K/AKT signaling pathway.
|mesh-terms=* Adult
* Aged
* Apoptosis
* Brain Neoplasms
* Cell Line, Tumor
* Cell Proliferation
* Cellular Senescence
* Female
* Fibronectins
* Gene Expression Regulation, Neoplastic
* Glioma
* Humans
* Male
* Middle Aged
* Neoplasm Invasiveness
* Phosphatidylinositol 3-Kinases
* Proto-Oncogene Proteins c-akt
* Signal Transduction
|keywords=* Apoptosis
* Cell cycle
* Fibronectin 1
* Gene expression data
* Glioma
* PI3K/AKT signaling pathway
* Senescence
|full-text-url=https://sci-hub.do/10.1159/000492096
}}
{{medline-entry
|title=Enhanced tissue regeneration potential of juvenile articular cartilage.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24043472
|abstract=Articular cartilage undergoes substantial age-related changes in molecular composition, matrix structure, and mechanical properties. These age-related differences between juvenile and adult cartilage manifest themselves as markedly distinct potentials for tissue repair and regeneration. To compare the biological properties and tissue regeneration capabilities of juvenile and adult bovine articular cartilage. Controlled laboratory study. Articular cartilage harvested from juvenile (age, 4 months) and adult (age, 6-8 years) bovine femoral condyles was cultured for 4 weeks to monitor chondrocyte migration, glycosaminoglycan content conservation, and new tissue formation. The cartilage cell density and proliferative activity were also compared. Additionally, the effects of age-related changes on cartilage gene expression were analyzed using the Affymetrix GeneChip array. Compared with adult cartilage, juvenile bovine cartilage demonstrated a significantly greater cell density, higher cell proliferation rate, increased cell outgrowth, elevated glycosaminoglycan content, and enhanced matrix metallopeptidase 2 activity. During 4 weeks in culture, only juvenile cartilage was able to generate new cartilaginous tissues, which exhibited pronounced labeling for proteoglycan and type II collagen but not type I collagen. With over 19,000 genes analyzed, distinctive gene expression profiles were identified. The genes mostly involved in cartilage growth and expansion, such as [[COL2A1]], [[COL9A1]], [[MMP2]], [[MMP14]], and [[TGFB3]], were upregulated in juvenile cartilage, whereas the genes primarily responsible for structural integrity, such as [[COMP]], [[FN1]], [[TIMP2]], [[TIMP3]], and [[BMP2]], were upregulated in adult cartilage. As the first comprehensive comparison between juvenile and adult bovine articular cartilage at the tissue, cellular, and molecular levels, the results strongly suggest that juvenile cartilage possesses superior chondrogenic activity and enhanced regenerative potential over its adult counterpart. Additionally, the differential gene expression profiles of juvenile and adult cartilage suggest possible mechanisms underlying cartilage age-related changes in their regeneration capabilities, structural components, and biological properties. The results of this comparative study between juvenile and adult bovine articular cartilage suggest an enhanced regenerative potential of juvenile cartilage tissue in the restoration of damaged articular cartilage.
|mesh-terms=* Aging
* Animals
* Cartilage, Articular
* Cattle
* Cell Count
* Cell Proliferation
* Chondrocytes
* Gene Expression Profiling
* Glycosaminoglycans
* Matrix Metalloproteinase 2
* Oligonucleotide Array Sequence Analysis
* Regeneration
|keywords=* adult
* aging
* articular cartilage
* biology of cartilage
* bovine
* cartilage regeneration
* cartilage repair
* chondrocyte
* gene expression
* juvenile
* knee
* migration
|full-text-url=https://sci-hub.do/10.1177/0363546513502945
}}
{{medline-entry
|title=Polyploidy impairs human aortic endothelial cell function and is prevented by nicotinamide phosphoribosyltransferase.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19846757
|abstract=Polyploid endothelial cells are found in aged and atherosclerotic arteries. However, whether increased chromosome content has an impact on endothelial cell function is unknown. We show here that human aortic endothelial cells become tetraploid as they approach replicative senescence. Furthermore, accumulation of tetraploid endothelial cells was accelerated during growth in high glucose. Interestingly, induction of polyploidy was completely prevented by modest overexpression of the NAD regenerating enzyme, nicotinamide phosphoribosyltransferase (Nampt). To determine the impact of polyploidy on endothelial cell function, independent of replicative senescence, we induced tetraploidy using the spindle poison, nocodazole. Global gene expression analyses of tetraploid endothelial cells revealed a dysfunctional phenotype characterized by a cell cycle arrest profile (decreased CCNE2/A2, [[RBL1]], BUB1B; increased CDKN1A) and increased expression of genes involved in inflammation (IL32, TNFRSF21/10C, PTGS1) and extracellular matrix remodeling (COL5A1, [[FN1]], MMP10/14). The protection from polyploidy conferred by Nampt was not associated with enhanced poly(ADP-ribose) polymerase-1 or sirtuin (SIRT) 2 activity, but with increased [[SIRT1]] activity, which reduced cellular reactive oxygen species and the associated oxidative stress stimulus for the induction of polyploidy. We conclude that human aortic endothelial cells are prone to chromosome duplication that, in and of itself, can induce characteristics of endothelial dysfunction. Moreover, the emergence of polyploid endothelial cells during replicative aging and glucose overload can be prevented by optimizing the Nampt-[[SIRT1]] axis.
|mesh-terms=* Aging
* Aorta
* Atherosclerosis
* Cell Cycle
* Cell Division
* Cytokines
* Endothelium, Vascular
* Extracellular Matrix
* Gene Expression Regulation
* Genes, Reporter
* Glucose
* Humans
* Inflammation
* Nicotinamide Phosphoribosyltransferase
* Nocodazole
* Polyploidy

|full-text-url=https://sci-hub.do/10.1152/ajpcell.00357.2009
}}
{{medline-entry
|title=The signaling hubs at the crossroad of longevity and age-related disease networks.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18793745
|abstract=The established human age-related disease proteins (ARDPs) and longevity-associated proteins (LAPs) together with their first-order interacting partners form scale-free networks which significantly overlap. About half of the common proteins are involved in signal transduction. These proteins are strongly interconnected and in turn form a common signaling network which comprises over 40% of all hubs (proteins with multiple interactions) in the human interactome. Along with the insulin pathway, the common signaling network is remarkably enriched with the focal adhesion and adherens junction proteins whose relation to the control of lifespan is yet to be fully addressed. The examples of such candidate proteins include several hubs, focal adhesion kinase [[PTK2]] and the extracellular proteins fibronectin [[FN1]], paxillin [[PXN]], and vinculin [[VCL]]. The results of the network-based analysis highlight the potential importance of these pathways, especially hubs, in linking the human longevity and age-related diseases.
|mesh-terms=* Adherens Junctions
* Aging
* Alzheimer Disease
* Animals
* Atherosclerosis
* Diabetes Mellitus, Type 2
* Fibronectins
* Focal Adhesion Kinase 1
* Focal Adhesions
* Humans
* Longevity
* Paxillin
* Protein Interaction Domains and Motifs
* Signal Transduction
* Vinculin

|full-text-url=https://sci-hub.do/10.1016/j.biocel.2008.08.026
}}
{{medline-entry
|title=Age-specific hormonal decline is accompanied by transcriptional changes in human sebocytes in vitro.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16805856
|abstract=The importance of hormones in endogenous aging has been displayed by recent studies performed on animal models and humans. To decipher the molecular mechanisms involved in aging we maintained human sebocytes at defined hormone-substituted conditions that corresponded to average serum levels of females from 20 (f20) to 60 (f60) years of age. The corresponding hormone receptor expression was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunocytochemistry. Cells at f60 produced significantly lower lipids than at f20. Increased mRNA and protein levels of c-Myc and increased protein levels of [[FN1]], which have been associated with aging, were detected in SZ95 sebocytes at f60 compared to those detected at f20 after 5 days of treatment. Expression profiling employing a cDNA microarray composed of 15 529 cDNAs identified 899 genes with altered expression levels at f20 vs. f60. Confirmation of gene regulation was performed by real-time RT-PCR. The functional annotation of these genes according to the Gene Ontology identified pathways related to mitochondrial function, oxidative stress, ubiquitin-mediated proteolysis, cell cycle, immune responses, steroid biosynthesis and phospholipid degradation - all hallmarks of aging. Twenty-five genes in common with those identified in aging kidneys and several genes involved in neurodegenerative diseases were also detected. This is the first report describing the transcriptome of human sebocytes and its modification by a cocktail of hormones administered in age-specific levels and provides an in vitro model system, which approximates some of the hormone-dependent changes in gene transcription that occur during aging in humans.
|mesh-terms=* Aging
* Cell Line
* Cell Proliferation
* Chromosomes, Human
* Fibronectins
* Gene Expression Profiling
* Gene Expression Regulation
* Hormones
* Humans
* Oligonucleotide Array Sequence Analysis
* Proto-Oncogene Proteins c-myc
* Sebaceous Glands
* Signal Transduction
* Transcription, Genetic

|full-text-url=https://sci-hub.do/10.1111/j.1474-9726.2006.00223.x
}}
{{medline-entry
|title=Auditory brain map, effects of age.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/3227262
|abstract=Brain maps of late auditory evoked cortical potentials were obtained with the Brain Atlas III system in school-aged children and adults. All subjects were judged as neurologically normal, right-handed, and having normal hearing. The stimulus was a 100 ms burst of 500 Hz pure tone at 75 dB HL presented separately to the left and right ear. The results showed a frontoparietal maximum of negative activity corresponding to N1 and designated as the focus of N1 ([[FN1]]). [[FN1]] had latencies of 108 ms (left stimulation (stim] and 113 ms (right stim) and amplitudes of -6.0 microV (left stim) and -4.8 microV (right stim) in children and a latency of 90 ms and an amplitude of -6.5 microV in adults. Among the children, more had ipsilateral than contralateral [[FN1]], usually on the right side. The distance between the centers of gravity of [[FN1]]s obtained on stimulation of the two ears was significantly smaller in the maps of children than adults (p less than 0.01). The present findings indicated that the topography of the electrical activity changes during adolescence.
|mesh-terms=* Adult
* Aging
* Brain Mapping
* Child
* Electroencephalography
* Evoked Potentials, Auditory
* Female
* Hearing
* Humans
* Male
* Middle Aged
* Reference Values

}}

FMO1

2021-05-12T15:37:57Z

OdysseusBot: Новая страница: «Dimethylaniline monooxygenase [N-oxide-forming] 1 (EC 1.14.13.8) (Dimethylaniline oxidase 1) (Fetal hepatic flavin-containing monooxygenase 1) (FMO 1) ==Publicat...»

Dimethylaniline monooxygenase [N-oxide-forming] 1 (EC 1.14.13.8) (Dimethylaniline oxidase 1) (Fetal hepatic flavin-containing monooxygenase 1) (FMO 1)

==Publications==

{{medline-entry
|title=Functional analysis and transcriptional output of the Göttingen minipig genome.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26573612
|abstract=In the past decade the Göttingen minipig has gained increasing recognition as animal model in pharmaceutical and safety research because it recapitulates many aspects of human physiology and metabolism. Genome-based comparison of drug targets together with quantitative tissue expression analysis allows rational prediction of pharmacology and cross-reactivity of human drugs in animal models thereby improving drug attrition which is an important challenge in the process of drug development. Here we present a new chromosome level based version of the Göttingen minipig genome together with a comparative transcriptional analysis of tissues with pharmaceutical relevance as basis for translational research. We relied on mapping and assembly of WGS (whole-genome-shotgun sequencing) derived reads to the reference genome of the Duroc pig and predict 19,228 human orthologous protein-coding genes. Genome-based prediction of the sequence of human drug targets enables the prediction of drug cross-reactivity based on conservation of binding sites. We further support the finding that the genome of Sus scrofa contains about ten-times less pseudogenized genes compared to other vertebrates. Among the functional human orthologs of these minipig pseudogenes we found [[HEPN1]], a putative tumor suppressor gene. The genomes of Sus scrofa, the Tibetan boar, the African Bushpig, and the Warthog show sequence conservation of all inactivating [[HEPN1]] mutations suggesting disruption before the evolutionary split of these pig species. We identify 133 Sus scrofa specific, conserved long non-coding RNAs (lncRNAs) in the minipig genome and show that these transcripts are highly conserved in the African pigs and the Tibetan boar suggesting functional significance. Using a new minipig specific microarray we show high conservation of gene expression signatures in 13 tissues with biomedical relevance between humans and adult minipigs. We underline this relationship for minipig and human liver where we could demonstrate similar expression levels for most phase I drug-metabolizing enzymes. Higher expression levels and metabolic activities were found for [[FMO1]], AKR/CRs and for phase II drug metabolizing enzymes in minipig as compared to human. The variability of gene expression in equivalent human and minipig tissues is considerably higher in minipig organs, which is important for study design in case a human target belongs to this variable category in the minipig. The first analysis of gene expression in multiple tissues during development from young to adult shows that the majority of transcriptional programs are concluded four weeks after birth. This finding is in line with the advanced state of human postnatal organ development at comparative age categories and further supports the minipig as model for pediatric drug safety studies. Genome based assessment of sequence conservation combined with gene expression data in several tissues improves the translational value of the minipig for human drug development. The genome and gene expression data presented here are important resources for researchers using the minipig as model for biomedical research or commercial breeding. Potential impact of our data for comparative genomics, translational research, and experimental medicine are discussed.
|mesh-terms=* Aging
* Animals
* Chromosomes
* Gene Expression
* Gene Expression Profiling
* Genome
* Humans
* Liver
* Pharmaceutical Preparations
* Pseudogenes
* Species Specificity
* Swine
* Swine, Miniature
* Transcription, Genetic

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647470
}}
{{medline-entry
|title=Quantitative analysis of FMO gene mRNA levels in human tissues.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16183778
|abstract=The developmentally and tissue-specific expression of flavin-containing monooxygenase (FMO) enzymes has been previously characterized in a number of animal species, including humans, mice, rats, and rabbits. In this study, we used sensitive real-time reverse transcription-polymerase chain reaction methodology to systematically quantify the steady-state mRNA levels of [[FMO1]], 2, 3, 4, and 5 in human tissues. We examined the developmental regulation of these enzymes in brain tissue. [[FMO1]] was found to be down-regulated in human adult brain. The amount of other FMO mRNAs in human brains in different age groups was not significantly different. The study also provided a systematic quantitative comparison of the steady-state mRNA levels of [[FMO1]] to 5 in several major human organs (i.e., liver, lung, kidney, small intestine, and brain). The nature of the quantitative analysis allowed a comprehensive comparison of each FMO mRNA in different tissues as well as among FMO isoforms in the same tissue. A comparison between fetal liver and adult liver showed that [[FMO1]] was the only FMO that was down-regulated; all other FMOs had greater amounts of mRNA in adult liver. [[FMO5]] was the most prominent FMO form detected in fetal liver. The [[FMO5]] mRNA level was nearly as abundant as [[FMO3]] in adult liver. Whereas other FMOs displayed a significant, dominant tissue-specific mRNA profile (i.e., [[FMO1]] in kidney, [[FMO2]] in lung, [[FMO3]] and [[FMO5]] in adult liver), [[FMO4]] mRNA was observed more broadly at relatively comparable levels in liver, kidney, lung, and small intestine.
|mesh-terms=* Aging
* Brain
* Down-Regulation
* Female
* Humans
* Intestine, Small
* Isoenzymes
* Kidney
* Liver
* Lung
* Male
* Oxygenases
* RNA, Messenger
* Reverse Transcriptase Polymerase Chain Reaction

|full-text-url=https://sci-hub.do/10.1124/dmd.105.006171
}}
{{medline-entry
|title=Effect of 17beta-estradiol and testosterone on the expression of flavin-containing monooxygenase and the toxicity of aldicarb to Japanese medaka, Oryzias latipes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12151634
|abstract=Previous studies in our laboratory indicated gender differences in salinity-enhanced acute toxicity of aldicarb in Japanese medaka with females being more susceptible. In the current study, the effects of the sex steroids, 17beta estradiol (E2) and testosterone (T) on aldicarb toxicity was examined. Adult Japanese medaka were separated by sex and exposed to 100 microg/l E2 or T for 6 days followed by exposure to the 96-h LC50 (0.5 mg/l) of aldicarb. The toxicity of aldicarb to adult males was significantly lowered by E2 and T whereby the mortality percentage was reduced to 23.3 /- 5.8% and 3.3 /- 5.8%, respectively, compared to the fish not receiving steroids (46.7 /- 5.8% mortality). In females, T caused significant reduction in aldicarb toxicity to 16.7 /- 5.8%, while E2 significantly enhanced the toxicity to 96.7 /- 5.8% mortality. Since the flavin-containing monooxygenase (FMO) enzyme system had been shown to play a critical role in aldicarb toxicity, the effect of E2 and T on FMO expression was examined. Gill FMO activity showed a direct correlation with the overall toxicity of aldicarb in both male and female medaka. Expression of [[FMO1]]-like protein was significantly reduced by T in male livers and gills, and T did not affect the expression of FMOs in female tissues. In contrast, E2 significantly reduced [[FMO1]]-like protein expression in male gills and female livers, as well as [[FMO3]] expression in both male and female livers, but significantly increased gill [[FMO1]] expression in females. Since aldicarb acts by inhibiting the enzyme cholinesterase (ChE), the effect of sex hormones on the activity of this enzyme was also examined. In both male and female medaka, T counteracted the inhibitory effect of aldicarb on muscle ChE. In male fish, E2 had similar effects but did not seem to counteract the ChE inhibition in females. In conclusion, E2 and T modulation of aldicarb toxicity in Japanese medaka seems to be mediated via alteration of gill FMO and ChE actitivies.
|mesh-terms=* Aldicarb
* Animals
* Cholinesterases
* Drug Interactions
* Estradiol
* Female
* Gills
* Insecticides
* Longevity
* Male
* Muscle, Skeletal
* Oryzias
* Oxygenases
* Sex Characteristics
* Testosterone
* Toxicity Tests, Acute

|full-text-url=https://sci-hub.do/10.1093/toxsci/68.2.381
}}
{{medline-entry
|title=Human hepatic flavin-containing monooxygenases 1 ([[FMO1]]) and 3 ([[FMO3]]) developmental expression.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11809920
|abstract=The flavin-containing monooxygenases (FMOs) are important for the metabolism of numerous therapeutics and toxicants. Six mammalian FMO genes ([[FMO1]]-6) have been identified, each exhibiting developmental and tissue- and species-specific expression patterns. Previous studies demonstrated that human hepatic [[FMO1]] is restricted to the fetus whereas [[FMO3]] is the major adult isoform. These studies failed to describe temporal expression patterns, the precise timing of the [[FMO1]]/[[FMO3]] switch, or potential control mechanisms. To address these questions, [[FMO1]] and [[FMO3]] were quantified in microsomal fractions from 240 human liver samples representing ages from 8 wk gestation to 18 y using Western blotting. [[FMO1]] expression was highest in the embryo (8-15 wk gestation; 7.8 /- 5.3 pmol/mg protein). Low levels of [[FMO3]] expression also were detectable in the embryo, but not in the fetus. [[FMO1]] suppression occurred within 3 d postpartum in a process tightly coupled to birth, but not gestational age. The onset of [[FMO3]] expression was highly variable, with most individuals failing to express this isoform during the neonatal period. [[FMO3]] was detectable in most individuals by 1-2 y of age and was expressed at intermediate levels until 11 y (12.7 /- 8.0 pmol/mg protein). These data suggest that birth is necessary, but not sufficient for the onset of [[FMO3]] expression. A gender-independent increase in [[FMO3]] expression was observed from 11 to 18 y of age (26.9 /- 8.6 pmol/mg protein). Finally, 2- to 20-fold interindividual variation in [[FMO1]] and [[FMO3]] protein levels were observed, depending on the age bracket.
|mesh-terms=* Adolescent
* Adult
* Aging
* Child
* Child, Preschool
* Embryo, Mammalian
* Female
* Fetus
* Gene Expression Regulation, Developmental
* Gene Expression Regulation, Enzymologic
* Gestational Age
* Humans
* Infant
* Infant, Newborn
* Isoenzymes
* Liver
* Male
* Microsomes, Liver
* Oxygenases

|full-text-url=https://sci-hub.do/10.1203/00006450-200202000-00018
}}
{{medline-entry
|title=The ontogeny of human drug-metabolizing enzymes: phase I oxidative enzymes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11805191
|abstract=Although some patterns are beginning to emerge, our knowledge of human phase I drug-metabolizing enzyme developmental expression remains far from complete. Expression has been observed as early as organogenesis, but this appears restricted to a few enzymes. At least two of the enzyme families that are expressed in the fetal liver exhibit a temporal switch in the immediate perinatal period (e.g., [[CYP3A7]] to CYP3A4/3A5 and [[FMO1]] to FMO3), whereas others show a progressive change in isoform expression through gestation (e.g., the class I alcohol dehydrogenases). Many of the phase I drug-metabolizing enzyme exhibit dynamic perinatal expression changes that are regulated primarily by mechanisms linked to birth and secondarily to maturity. A few of these enzymes are not detectable until well after birth, suggesting that birth is necessary but not sufficient for the onset of expression (e.g., CYP1A2). Tissue-specific expression adds to the complexity during ontogeny. For example, [[CYP3A7]] expression is restricted to the fetal liver. However, with few exceptions, complete temporal relationship information during development is not known. Furthermore, most studies have concentrated on hepatic expression and much less is known about extrahepatic developmental events.
|mesh-terms=* Aging
* Alcohol Dehydrogenase
* Cytochrome P-450 Enzyme System
* Humans
* Mixed Function Oxygenases
* Monoamine Oxidase
* Pharmaceutical Preparations
* Pharmacokinetics

|full-text-url=https://sci-hub.do/10.1124/jpet.300.2.355
}}
{{medline-entry
|title=Age-related susceptibility to 3,3'-iminodipropionitrile-induced olfactory mucosal damage.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10192216
|abstract=3,3'-Iminodipropionitrile (IDPN) causes degeneration of the olfactory mucosa (OM) in rodents following systemic exposure. Approximately 30% of the OM degenerates in 21-day- and 10-week-old rats following a single 200 or 400 mg/kg intraperitoneal (i.p.) dose of IDPN, whereas 100% olfactory mucosal degeneration occurred in 21-month-old rats. Age-related changes in the flavin-containing monooxygenases (FMOs) or heat shock protein 70 (HSP70) were hypothesized to be responsible for altered olfactory mucosal susceptibility to IDPN. FMO activity in OM was higher than in liver in rats up to 40 weeks of age. Western blots of OM and liver revealed no change in [[FMO1]] protein; however, [[FMO2]], 3, and 5 decreased in olfactory microsomes with age. [[FMO3]] and [[FMO5]] increased in liver microsomes with age. Heat shock protein 70 did not differ between 10-week- and 10-month-old rats in either tissue. The mechanism underlying the increased susceptibility of older rats is likely a complex interaction between the activities of one or more of the enzymes involved in IDPN metabolism in OM and liver.
|mesh-terms=* Aging
* Animals
* Blotting, Western
* Cytosol
* HSP70 Heat-Shock Proteins
* Isoenzymes
* Liver
* Male
* Microsomes
* Nitriles
* Olfactory Mucosa
* Oxygenases
* Rats

|full-text-url=https://sci-hub.do/10.1016/s0197-4580(98)00104-3
}}

FMN2

2021-05-12T15:37:54Z

OdysseusBot: Новая страница: «Formin-2 ==Publications== {{medline-entry |title=Genomic regulation of senescence and innate immunity signaling in the retinal pigment epithelium. |pubmed-url=h...»

Formin-2

==Publications==

{{medline-entry
|title=Genomic regulation of senescence and innate immunity signaling in the retinal pigment epithelium.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25963977
|abstract=The tumor suppressor p53 is a major regulator of genes important for cell cycle arrest, senescence, apoptosis, and innate immunity, and has recently been implicated in retinal aging. In this study we sought to identify the genetic networks that regulate p53 function in the retina using quantitative trait locus (QTL) analysis. First we examined age-associated changes in the activation and expression levels of p53; known p53 target proteins and markers of innate immune system activation in primary retinal pigment epithelial ([[RPE]]) cells that were harvested from young and aged human donors. We observed increased expression of p53, activated caspase-1, [[CDKN1A]], [[[[CDKN2A]]]] (p16INK4a), [[TLR4]], and IFNα in aged primary [[RPE]] cell lines. We used the Hamilton Eye Institute (HEI) retinal dataset ( www.genenetwork.org ) to identify genomic loci that modulate expression of genes in the p53 pathway in recombinant inbred BXD mouse strains using a QTL systems biology-based approach. We identified a significant trans-QTL on chromosome 1 (region 172-177 Mb) that regulates the expression of Cdkn1a. Many of the genes in this QTL locus are involved in innate immune responses, including Fc receptors, interferon-inducible family genes, and formin 2. Importantly, we found an age-related increase in [[FCGR3A]] and [[FMN2]] and a decrease in [[IFI16]] levels in [[RPE]] cultures. There is a complex multigenic innate immunity locus that controls expression of genes in the p53 pathway in the [[RPE]], which may play an important role in modulating age-related changes in the retina.
|mesh-terms=* Adult
* Aged, 80 and over
* Aging
* Animals
* Apoptosis
* Caspases
* Caspases, Initiator
* Cell Line
* Cyclin-Dependent Kinase Inhibitor p16
* Cyclin-Dependent Kinase Inhibitor p21
* Gene Expression Regulation
* Humans
* Immunity, Innate
* Interferon-alpha
* Interferon-gamma
* Mice
* Mice, Inbred BALB C
* Mice, Inbred C57BL
* Mice, Inbred DBA
* Primary Cell Culture
* Quantitative Trait Loci
* Retinal Pigment Epithelium
* Signal Transduction
* Toll-Like Receptor 4
* Tumor Suppressor Protein p53

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450138
}}

FLT4

2021-05-12T15:37:51Z

OdysseusBot: Новая страница: «Vascular endothelial growth factor receptor 3 precursor (EC 2.7.10.1) (VEGFR-3) (Fms-like tyrosine kinase 4) (FLT-4) (Tyrosine-protein kinase receptor FLT4) [VEGF...»

Vascular endothelial growth factor receptor 3 precursor (EC 2.7.10.1) (VEGFR-3) (Fms-like tyrosine kinase 4) (FLT-4) (Tyrosine-protein kinase receptor FLT4) [VEGFR3]

==Publications==

{{medline-entry
|title=Impact of Aging on the Phenotype of Invariant Natural Killer T Cells in Mouse Thymus.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33193368
|abstract=Invariant natural killer T (iNKT) cells represent a subclass of T cells possessing a restricted repertoire of T cell receptors enabling them to recognize lipid derived ligands. iNKT cells are continuously generated in thymus and differentiate into three main subpopulations: iNKT1, iNKT2, and iNKT17 cells. We investigated the transcriptomes of these subsets comparing cells isolated from young adult (6-10 weeks old) and aged BALB/c mice (25-30 weeks of age) in order to identify genes subject to an age-related regulation of expression. These time points were selected to take into consideration the consequences of thymic involution that radically alter the existing micro-milieu. Significant differences were detected in the expression of histone genes affecting all iNKT subsets. Also the proliferative capacity of iNKT cells decreased substantially upon aging. Several genes were identified as possible candidates causing significant age-dependent changes in iNKT cell generation and/or function such as genes coding for granzyme A, ZO-1, [[EZH2]], [[SOX4]], [[IGF1]] receptor, [[FLT4]], and CD25. Moreover, we provide evidence that [[IL2]] differentially affects homeostasis of iNKT subsets with iNKT17 cells engaging a unique mechanism to respond to [[IL2]] by initiating a slow rate of proliferation.

|keywords=* IL2
* aging
* invariant natural killer T cells
* thymus
* transcriptome
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662090
}}

FLT3

2021-05-12T15:37:48Z

OdysseusBot: Новая страница: «Receptor-type tyrosine-protein kinase FLT3 precursor (EC 2.7.10.1) (FL cytokine receptor) (Fetal liver kinase-2) (FLK-2) (Fms-like tyrosine kinase 3) (FLT-3) (Ste...»

Receptor-type tyrosine-protein kinase FLT3 precursor (EC 2.7.10.1) (FL cytokine receptor) (Fetal liver kinase-2) (FLK-2) (Fms-like tyrosine kinase 3) (FLT-3) (Stem cell tyrosine kinase 1) (STK-1) (CD135 antigen) [CD135] [FLK2] [STK1]

==Publications==

{{medline-entry
|title=Sequential acquisition of mutations in myelodysplastic syndromes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28978821
|abstract=Recent progress in next-generation sequencing technologies allows us to discover frequent mutations throughout the coding regions of myelodysplastic syndromes (MDS), potentially providing us with virtually a complete spectrum of driver mutations in this disease. As shown by many study groups these days, such driver mutations are acquired in a gene-specific fashion. For instance, [[DDX41]] mutations are observed in germline cells long before MDS presentation. In blood samples from healthy elderly individuals, somatic [[DNMT3A]] and [[TET2]] mutations are detected as age-related clonal hematopoiesis and are believed to be a risk factor for hematological neoplasms. In MDS, mutations of genes such as [[NRAS]] and [[FLT3]], designated as Type-1 genes, may be significantly associated with leukemic evolution. Another type (Type-2) of genes, including [[RUNX1]] and [[GATA2]], are related to progression from low-risk to high-risk MDS. Overall, various driver mutations are sequentially acquired in MDS, at a specific time, in either germline cells, normal hematopoietic cells, or clonal MDS cells.
|mesh-terms=* Aging
* DEAD-box RNA Helicases
* Genome, Human
* Humans
* Mutation
* Myelodysplastic Syndromes
* Prognosis
|keywords=* Germline mutations
* Myelodysplastic syndromes
* Secondary acute myeloid leukemia
* Somatic mutations
|full-text-url=https://sci-hub.do/10.11406/rinketsu.58.1828
}}
{{medline-entry
|title=RAS mutations contribute to evolution of chronic myelomonocytic leukemia to the proliferative variant.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20371679
|abstract=The biological and clinical heterogeneity of chronic myelomonocytic leukemia features renders its classification difficult. Moreover, because of the limited knowledge of the mechanisms involved in malignant evolution, chronic myelomonocytic leukemia remains a diagnostic and therapeutic challenge and a poor prognosis disease. We aimed to verify the biological and clinical significance of the discrimination, based on the leukocyte count, between myelodysplastic chronic myelomonocytic leukemia (MD-CMML) and myeloproliferative chronic myelomonocytic leukemia (MP-CMML). Peripheral blood samples from 22 patients classified as MD-CMML and 18 as MP-CMML were collected at different time points during disease course, and patients' clinical characteristics were examined. RAS mutational screening was done by sequencing and, for each substitution identified, a highly selective allele-specific PCR was set up to screen all specimens. MP-CMML patients showed a significantly poorer survival (P = 0.003) and a higher frequency of RAS mutations (P = 0.033) by sequencing compared with MD-CMML. Overall, five MD-CMML patients progressed to myeloproliferative disease: in two, allele-specific PCR unveiled low levels of the RAS mutations predominating in the myeloproliferative phase at the time of myelodysplastic disease, documenting for the first time the expansion of a RAS mutated clone in concomitance with chronic myelomonocytic leukemia evolution. Moreover, one of the progressed patients harbored the [[FLT3]]-ITD and two MP-CMML patients presented with the [[JAK2]] V617F substitution. All these lesions were mutually exclusive. Our results strongly suggest RAS mutations to function as a secondary event that contributes to development of the chronic myelomonocytic leukemia variant with the poorer prognosis (MP-CMML) and therefore advise their detection to be implemented in chronic myelomonocytic leukemia diagnostics and monitoring.
|mesh-terms=* Aged
* Aged, 80 and over
* Animals
* Colony-Forming Units Assay
* Disease Progression
* Evolution, Molecular
* Female
* Genes, ras
* Guanosine Triphosphate
* Humans
* Janus Kinase 2
* Leukemia, Myelomonocytic, Chronic
* Life Expectancy
* Male
* Mice
* Middle Aged
* Mutation
* Myelodysplastic Syndromes
* Myeloproliferative Disorders
* NIH 3T3 Cells
* Prognosis
* Proto-Oncogene Proteins
* Proto-Oncogene Proteins p21(ras)
* Survival Rate
* fms-Like Tyrosine Kinase 3
* ras Proteins

|full-text-url=https://sci-hub.do/10.1158/1078-0432.CCR-09-2112
}}
{{medline-entry
|title=The relationship of patient age to the pathobiology of the clonal myeloid diseases.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15112149
|abstract=The incidence of the major clonal myeloid diseases, clonal cytopenias, acute, subacute (oligoblastic), and chronic myelogenous leukemia, polycythemia vera, thrombocythemia, and idiopathic myelofibrosis increases in a log-linear manner from young adulthood through advanced age. In older patients, diseases requiring cytotoxic treatment are more difficult and less successful to manage because comorbid conditions and poor performance status are more prevalent, decreasing the tolerance to therapy and increasing the frequency of side effects. This age effect is highlighted by the dramatically less favorable outcome in older than younger patients with acute myeloid leukemia with similar "favorable" cytogenetic changes. In addition, in acute and subacute myeloid leukemia in older patients, the disease is intrinsically more resistant to therapy. Overexpression of drug resistance genes and unfavorable genetic mutations are more prevalent in older patients and provide evidence that acute myeloid leukemia is often qualitatively different in these patients. The gradient of age effects is continuous; the frequency of poor outcome increasing by decade (or less). The decline in survival becomes especially steep as quinquagenarians (50-year-olds) age to nonagenarians (90-year-olds). Although improved drug schedules have led to significant improvements in event-free survival in younger patients, these improvements have been far less evident in older patients. New approaches, especially the development of drugs aimed at new targets, will be required to obtain a high frequency of long-term remissions in older patients. Agents that reverse inherent cellular drug resistance, farnesyltransferase inhibitors, BCL-2 inhibitors, and [[FLT3]] inhibitors are early examples of such approaches.
|mesh-terms=* Aged
* Aging
* Bone Marrow Diseases
* Cytogenetics
* Hematopoietic Stem Cells
* Humans
* Leukemia, Myeloid
* Myelodysplastic Syndromes
* Myeloproliferative Disorders

|full-text-url=https://sci-hub.do/10.1053/j.seminoncol.2003.12.029
}}
{{medline-entry
|title=Regulation of dendritic cell expansion in aged athymic nude mice by [[FLT3]] ligand.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15036393
|abstract=This report describes age-related alterations of dendritic cells (DC) distribution in nude athymic mice in vivo and reversal of certain age-dependent defects by an in vivo administration of hematopoietic growth factor [[FLT3]] ligand ([[FLT3]]L). There are decreased percentages of CD11c( ) DC in the bone marrow and spleen and a reduced expression of MHC class II and [[CD86]] molecules on DC in old nude mice. The decreased levels of CD11c( ) DC were due to the CD8alpha(-) DC subset. The distribution of CD11c( ) CD8alpha( ) DC in the lymphoid tissues was not different in young and old mice. The effect of in vivo administration of [[FLT3]]L on the generation and distribution of DC in the lymphoid tissues in young and old nude mice was also evaluated. Although, [[FLT3]]L had a higher inductive potential on the expansion of DC from the bone marrow in the elderly mice, the total level of CD11c( ) DC in the young animals was still significantly higher as compared to the old animals. Interestingly, [[FLT3]]L induced a pronounced redistribution and accumulation of MHC class II( ) DC in the lymphoid tissues in old mice, markedly increased the accumulation of CD8alpha(-) DC in the bone marrow in both young and old nude mice, and elevated both CD8alpha(-) and CD8alpha( ) DC in the spleen in young mice. However, only the level of CD8alpha( ) DC was up regulated in the spleen in old athymic mice after [[FLT3]]L-based therapy. In summary, abnormalities in DC generation and distribution in old athymic mice could be, in part, circumvented by the in vivo administration of [[FLT3]]L.
|mesh-terms=* Aging
* Animals
* Antigens, CD
* B7-2 Antigen
* Bone Marrow
* CD11c Antigen
* CD8 Antigens
* Cell Division
* Dendritic Cells
* Flow Cytometry
* Histocompatibility Antigens Class II
* Male
* Membrane Glycoproteins
* Membrane Proteins
* Mice
* Mice, Nude
* Spleen

|full-text-url=https://sci-hub.do/10.1016/j.exger.2004.01.003
}}
{{medline-entry
|title=[[FLT3]], RAS, and [[TP53]] mutations in elderly patients with acute myeloid leukemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11369655
|abstract=The prevalence and significance of genetic abnormalities in older patients with acute myeloid leukemia (AML) are unknown. Polymerase chain reactions and single-stranded conformational polymorphism analyses were used to examine 140 elderly AML patients enrolled in the Southwest Oncology Group study 9031 for [[FLT3]], RAS, and [[TP53]] mutations, which were found in 34%, 19%, and 9% of patients, respectively. All but one of the [[FLT3]] (46 of 47) mutations were internal tandem duplications (ITDs) within exons 11 and 12. In the remaining case, a novel internal tandem triplication was found in exon 11. [[FLT3]] ITDs were associated with higher white blood cell counts, higher peripheral blast percentages, normal cytogenetics, and less disease resistance. All RAS mutations (28 of 28) were missense point mutations in codons 12, 13, or 61. RAS mutations were associated with lower peripheral blast and bone marrow blast percentages. Only 2 of 47 patients with [[FLT3]] ITDs also had a RAS mutation, indicating a significant negative association between [[FLT3]] and RAS mutations (P =.0013). Most [[TP53]] mutations (11 of 12) were missense point mutations in exons 5 to 8 and were associated with abnormal cytogenetics, especially abnormalities in both chromosomes 5 and 7. [[FLT3]] and RAS mutations were not associated with inferior clinical outcomes, but [[TP53]] mutations were associated with a worse overall survival (median 1 versus 8 months, P =.0007). These results indicate that mutations in [[FLT3]], RAS, or [[TP53]] are common in older patients with AML and are associated with specific AML phenotypes as defined by laboratory values, cytogenetics, and clinical outcomes. (Blood. 2001;97:3589-3595)
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Exons
* Gene Frequency
* Genes, ras
* Humans
* Leukemia, Myeloid, Acute
* Middle Aged
* Mutation
* Polymerase Chain Reaction
* Polymorphism, Single-Stranded Conformational
* Prognosis
* Proto-Oncogene Proteins
* Receptor Protein-Tyrosine Kinases
* Tumor Suppressor Protein p53
* fms-Like Tyrosine Kinase 3

|full-text-url=https://sci-hub.do/10.1182/blood.v97.11.3589
}}

FLNA

2021-05-12T15:37:44Z

OdysseusBot: Новая страница: «Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) [FLN] [FLN1] ==Publi...»

Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) [FLN] [FLN1]

==Publications==

{{medline-entry
|title=[[SQSTM1]]/p62 mediates crosstalk between autophagy and the UPS in DNA repair.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27391408
|abstract=[[SQSTM1]]/p62 (sequestosome 1) selectively targets polyubiquitinated proteins for degradation via macroautophagy and the proteasome. Additionally, [[SQSTM1]] shuttles between the cytoplasmic and nuclear compartments, although its role in the nucleus is relatively unknown. Here, we report that [[SQSTM1]] dynamically associates with DNA damage foci (DDF) and regulates DNA repair. Upon induction of DNA damage [[SQSTM1]] interacts with [[FLNA]] (filamin A), which has previously been shown to recruit DNA repair protein [[RAD51]] ([[RAD51]] recombinase) to double-strand breaks and facilitate homologous recombination ([[HR]]). [[SQSTM1]] promotes proteasomal degradation of [[FLNA]] and [[RAD51]] within the nucleus, resulting in reduced levels of nuclear [[RAD51]] and slower DNA repair. [[SQSTM1]] regulates the ratio between [[HR]] and nonhomologous end joining (NHEJ) by promoting the latter at the expense of the former. This [[SQSTM1]]-dependent mechanism mediates the effect of macroautophagy on DNA repair. Moreover, nuclear localization of [[SQSTM1]] and its association with DDF increase with aging and are prevented by life-span-extending dietary restriction, suggesting that an imbalance in the mechanism identified here may contribute to aging and age-related diseases.
|mesh-terms=* Animals
* Autophagy
* Cell Nucleus
* DNA Damage
* DNA Repair
* Filamins
* Kinetics
* Mice, Inbred C57BL
* Models, Biological
* Proteasome Endopeptidase Complex
* Protein Transport
* Proteolysis
* Rad51 Recombinase
* Sequestosome-1 Protein
* Ubiquitin
|keywords=* DNA damage
* SQSTM1
* aging
* autophagy
* homologous recombination
* nonhomologous end joining
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391493
}}

FLCN

2021-05-12T15:37:42Z

OdysseusBot: Новая страница: «Folliculin (BHD skin lesion fibrofolliculoma protein) (Birt-Hogg-Dube syndrome protein) [BHD] ==Publications== {{medline-entry |title=Loss of the Birt-Hogg-Dub...»

Folliculin (BHD skin lesion fibrofolliculoma protein) (Birt-Hogg-Dube syndrome protein) [BHD]

==Publications==

{{medline-entry
|title=Loss of the Birt-Hogg-Dubé gene product folliculin induces longevity in a hypoxia-inducible factor-dependent manner.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23566034
|abstract=Signaling through the hypoxia-inducible factor hif-1 controls longevity, metabolism, and stress resistance in Caenorhabditis elegans. Hypoxia-inducible factor (HIF) protein levels are regulated through an evolutionarily conserved ubiquitin ligase complex. Mutations in the [[VHL]] gene, encoding a core component of this complex, cause a multitumor syndrome and renal cell carcinoma in humans. In the nematode, deficiency in vhl-1 promotes longevity mediated through HIF-1 stabilization. However, this longevity assurance pathway is not yet understood. Here, we identify folliculin ([[FLCN]]) as a novel interactor of the hif-1/vhl-1 longevity pathway. [[FLCN]] mutations cause Birt-Hogg-Dubé syndrome in humans, another tumor syndrome with renal tumorigenesis reminiscent of the [[VHL]] disease. Loss of the C. elegans ortholog of [[FLCN]] F22D3.2 significantly increased lifespan and enhanced stress resistance in a hif-1-dependent manner. F22D3.2, vhl-1, and hif-1 control longevity by a mechanism distinct from insulin-like signaling. Daf-16 deficiency did not abrogate the increase in lifespan mediated by flcn-1. These findings define [[FLCN]] as a player in HIF-dependent longevity signaling and connect organismal aging, stress resistance, and regulation of longevity with the formation of renal cell carcinoma.
|mesh-terms=* Animals
* Birt-Hogg-Dube Syndrome
* Caenorhabditis elegans
* Caenorhabditis elegans Proteins
* Cullin Proteins
* Forkhead Transcription Factors
* Gene Expression Regulation, Developmental
* Humans
* Longevity
* Mutation
* Protein Stability
* Proto-Oncogene Proteins
* RNA, Messenger
* Sequence Homology, Amino Acid
* Transcription Factors
* Tumor Suppressor Proteins
|keywords=* Birt-Hogg-Dubé
* C. elegans
* Vhl
* folliculin
* hif
* longevity
|full-text-url=https://sci-hub.do/10.1111/acel.12081
}}

FKRP

2021-05-12T15:37:39Z

OdysseusBot: Новая страница: «Fukutin-related protein (EC 2.4.2.-) (Ribitol-5-phosphate transferase) ==Publications== {{medline-entry |title=Progressive Dystrophic Pathology in Diaphragm and...»

Fukutin-related protein (EC 2.4.2.-) (Ribitol-5-phosphate transferase)

==Publications==

{{medline-entry
|title=Progressive Dystrophic Pathology in Diaphragm and Impairment of Cardiac Function in [[FKRP]] P448L Mutant Mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27711214
|abstract=Mutations in the gene for fukutin-related protein represent a subset of muscular dystrophies known as dystroglycanopathies characterized by loss of functionally-glycosylated-alpha-dystroglycan and a wide range of dystrophic phenotypes. Mice generated by our lab containing the P448L mutation in the fukutin-related protein gene demonstrate the dystrophic phenotype similar to that of LGMD2I. Here we examined the morphology of the heart and diaphragm, focusing on pathology of diaphragm and cardiac function of the mutant mice for up to 12 months. Both diaphragm and heart lack clear expression of functionally-glycosylated-alpha-dystroglycan throughout the observed period. The diaphragm undergoes progressive deterioration in histology with increasing amount of centranucleation and inflammation. Large areas of mononuclear cell infiltration and fibrosis of up to 60% of tissue area were detected as early as 6 months of age. Despite a less severe morphology with only patches of mononuclear cell infiltration and fibrosis of ~5% by 12 months of age in the heart, cardiac function is clearly affected. High frequency ultrasound reveals a smaller heart size up to 10 months of age. There are significant increases in myocardial thickness and decrease in cardiac output through 12 months. Dysfunction in the heart represents a key marker for evaluating experimental therapies aimed at cardiac muscle.
|mesh-terms=* Aging
* Animals
* Diaphragm
* Disease Progression
* Dystroglycans
* Electrocardiography
* Glycosylation
* Heart
* Mice
* Mice, Inbred C57BL
* Muscular Dystrophies
* Mutation
* Myocardium
* Pentosyltransferases
* Phenotype
* Proteins
* Transferases

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053477
}}

FKBP5

2021-05-12T15:37:36Z

OdysseusBot: Новая страница: «Peptidyl-prolyl cis-trans isomerase FKBP5 (EC 5.2.1.8) (PPIase FKBP5) (51 kDa FK506-binding protein) (51 kDa FKBP) (FKBP-51) (54 kDa progesterone receptor-associa...»

Peptidyl-prolyl cis-trans isomerase FKBP5 (EC 5.2.1.8) (PPIase FKBP5) (51 kDa FK506-binding protein) (51 kDa FKBP) (FKBP-51) (54 kDa progesterone receptor-associated immunophilin) (Androgen-regulated protein 6) (FF1 antigen) (FK506-binding protein 5) (FKBP-5) (FKBP54) (p54) (HSP90-binding immunophilin) (Rotamase) [AIG6] [FKBP51]

==Publications==

{{medline-entry
|title=Epigenetic upregulation of [[FKBP5]] by aging and stress contributes to NF-κB-driven inflammation and cardiovascular risk.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31113877
|abstract=Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are unclear. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress along the lifespan could confer disease risk through epigenetic effects on molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with experiments in cells, we report that [[FKBP5]], a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total [i]n[/i] > 3,000), aging synergized with stress-related phenotypes, measured with childhood trauma and major depression questionnaires, to epigenetically up-regulate [i][[FKBP5]][/i] expression. These age/stress-related epigenetic effects were recapitulated in a cellular model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher [i][[FKBP5]][/i] mRNA with a proinflammatory profile and altered NF-κB-related gene networks. Accordingly, experiments in immune cells showed that higher [i][[FKBP5]][/i] promotes inflammation by strengthening the interactions of NF-κB regulatory kinases, whereas opposing [[FKBP5]] either by genetic deletion (CRISPR/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-κB. Further, the age/stress-related epigenetic signature enhanced [i][[FKBP5]][/i] response to NF-κB through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that aging/stress-driven [[FKBP5]]-NF-κB signaling mediates inflammation, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities.
|mesh-terms=* Aging
* Cardiovascular Diseases
* Cellular Senescence
* Child, Preschool
* Depressive Disorder, Major
* Epigenesis, Genetic
* Female
* Genome-Wide Association Study
* Humans
* Inflammation
* Male
* NF-kappa B
* Risk Factors
* Signal Transduction
* Stress, Psychological
* Tacrolimus Binding Proteins
* Up-Regulation
|keywords=* FKBP5
* aging
* epigenetics
* inflammation
* psychosocial stress
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561294
}}
{{medline-entry
|title=The common functional [[FKBP5]] variant rs1360780 is associated with altered cognitive function in aged individuals.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25331639
|abstract=The common single nucleotide polymorphism (SNP) rs1360780 (C/T) of the FK506 Binding Protein 5 ([[FKBP5]]) gene has been reported to be associated with an altered response of the hypothalamic-pituitary-adrenal (HPA) axis and the development of stress-related psychiatric disorders such as posttraumatic stress disorder (PTSD). In the present study, we examined whether this SNP is associated with cognitive function in a non-clinical population. The full versions of the Wechsler Memory Scale-Revised and Wechsler Adult Intelligence Scale-Revised were administered to 742 and 627 Japanese individuals, respectively, followed by genotyping of rs1360780 by the TaqMan 5'-exonuclease allelic discrimination assay. For both cognitive tests, we found significantly poorer attention/concentration (working memory) in aged (>50 years old) individuals carrying the T allele compared with their counterparts. This finding accords with an altered HPA axis and vulnerability to stress-related psychiatric disorders.
|mesh-terms=* Aged
* Aging
* Cognition
* Female
* Gene Frequency
* Genetic Association Studies
* Genotype
* Humans
* Hypothalamo-Hypophyseal System
* Male
* Memory, Short-Term
* Middle Aged
* Polymorphism, Single Nucleotide
* Stress Disorders, Post-Traumatic
* Tacrolimus Binding Proteins

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204028
}}
{{medline-entry
|title=Age-associated epigenetic upregulation of the [[FKBP5]] gene selectively impairs stress resiliency.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25191701
|abstract=Single nucleotide polymorphisms (SNPs) in the FK506 binding protein 5 ([[FKBP5]]) gene combine with traumatic events to increase risk for post-traumatic stress and major depressive disorders (PTSD and MDD). These SNPs increase [[FKBP5]]1 protein expression through a mechanism involving demethylation of the gene and altered glucocorticoid signaling. Aged animals also display elevated [[FKBP5]]1 levels, which contribute to impaired resiliency to depressive-like behaviors through impaired glucocorticoid signaling, a phenotype that is abrogated in [[FKBP5]]-/- mice. But the age of onset and progressive stability of these phenotypes remain unknown. Moreover, it is unclear how [[FKBP5]] deletion affects other glucocorticoid-dependent processes or if age-associated increases in [[FKBP5]]1 expression are mediated through a similar epigenetic process caused by SNPs in the [[FKBP5]] gene. Here, we show that [[FKBP5]]1-mediated impairment in stress resiliency and glucocorticoid signaling occurs by 10 months of age and this increased over their lifespan. Surprisingly, despite these progressive changes in glucocorticoid responsiveness, [[FKBP5]]-/- mice displayed normal longevity, glucose tolerance, blood composition and cytokine profiles across lifespan, phenotypes normally associated with glucocorticoid signaling. We also found that methylation of Fkbp5 decreased with age in mice, a process that likely explains the age-associated increases in [[FKBP5]]1 levels. Thus, epigenetic upregulation of [[FKBP5]]1 with age can selectively impair psychological stress-resiliency, but does not affect other glucocorticoid-mediated physiological processes. This makes [[FKBP5]]1 a unique and attractive therapeutic target to treat PTSD and MDD. In addition, aged wild-type mice may be a useful model for investigating the mechanisms of [[FKBP5]] SNPs associated with these disorders.
|mesh-terms=* Aging
* Animals
* DNA Methylation
* Depressive Disorder, Major
* Epigenesis, Genetic
* Hydrocortisone
* Longevity
* Mice
* Mice, Knockout
* Polymorphism, Single Nucleotide
* Resilience, Psychological
* Stress Disorders, Post-Traumatic
* Stress, Psychological
* Tacrolimus Binding Proteins
* Up-Regulation

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156438
}}
{{medline-entry
|title=Role of [[FKBP5]] in emotion processing: results on amygdala activity, connectivity and volume.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24756342
|abstract=Accumulating evidence suggests a role of [[FKBP5]], a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in [[FKBP5]] on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for [[FKBP5]] rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of [[FKBP5]] on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of [[FKBP5]] in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.
|mesh-terms=* Adult
* Aging
* Amygdala
* Child
* Child, Preschool
* Depressive Disorder
* Emotions
* Environment
* Family
* Female
* Genotype
* Humans
* Infant
* Magnetic Resonance Imaging
* Male
* Polymorphism, Single Nucleotide
* Prefrontal Cortex
* Prospective Studies
* Psychiatric Status Rating Scales
* Retrospective Studies
* Surveys and Questionnaires
* Tacrolimus Binding Proteins
* Young Adult

|full-text-url=https://sci-hub.do/10.1007/s00429-014-0729-5
}}
{{medline-entry
|title=Cell intrinsic role of COX-2 in pancreatic cancer development.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22784710
|abstract=COX-2 is upregulated in pancreatic ductal adenocarcinomas (PDAC). However, how COX-2 promotes PDAC development is unclear. While previous studies have evaluated the efficacy of COX-2 inhibition via the use of nonsteroidal anti-inflammatory drugs (NSAID) or the COX-2 inhibitor celecoxib in PDAC models, none have addressed the cell intrinsic versus microenvironment roles of COX-2 in modulating PDAC initiation and progression. We tested the cell intrinsic role of COX-2 in PDAC progression using both loss-of-function and gain-of-function approaches. Cox-2 deletion in Pdx1 pancreatic progenitor cells significantly delays the development of PDAC in mice with K-ras activation and Pten haploinsufficiency. Conversely, COX-2 overexpression promotes early onset and progression of PDAC in the K-ras mouse model. Loss of [[PTEN]] function is a critical factor in determining lethal PDAC onset and overall survival. Mechanistically, COX-2 overexpression increases p-AKT levels in the precursor lesions of Pdx1( ); K-ras(G12D)(/ ); Pten(lox)(/ ) mice in the absence of Pten LOH. In contrast, Cox-2 deletion in the same setting diminishes p-AKT levels and delays cancer progression. These data suggest an important cell intrinsic role for COX-2 in tumor initiation and progression through activation of the PI3K/AKT pathway. PDAC that is independent of intrinsic COX-2 expression eventually develops with decreased [[FKBP5]] and increased GRP78 expression, two alternate pathways leading to AKT activation. Together, these results support a cell intrinsic role for COX-2 in PDAC development and suggest that while anti-COX-2 therapy may delay the development and progression of PDAC, mechanisms known to increase chemoresistance through AKT activation must also be overcome.
|mesh-terms=* Animals
* Carcinoma, Pancreatic Ductal
* Celecoxib
* Cell Membrane
* Cyclooxygenase 2
* Disease Models, Animal
* Disease Progression
* Enzyme Activation
* Feedback, Physiological
* Gene Deletion
* Gene Targeting
* Heat-Shock Proteins
* Homeodomain Proteins
* Integrases
* Life Expectancy
* Mice
* PTEN Phosphohydrolase
* Pancreatic Neoplasms
* Precancerous Conditions
* Proto-Oncogene Proteins c-akt
* Proto-Oncogene Proteins p21(ras)
* Pyrazoles
* Sulfonamides
* Survival Analysis
* Tacrolimus Binding Proteins
* Trans-Activators
* Up-Regulation

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469770
}}
{{medline-entry
|title=[[FKBP5]] polymorphisms and antidepressant response in geriatric depression.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19676097
|abstract=Genetic variation at the [[FKBP5]] locus has been reported to affect clinical outcomes in patients treated with antidepressant medications in several studies. However, other reports have not confirmed this association. [[FKBP5]] may regulate the sensitivity of the hypothalamic-pituitary-adrenal axis. We tested two [[FKBP5]] single nucleotide polymorphisms (rs1360780 and rs3800373) in a sample of 246 geriatric patients treated for 8 weeks in a double-blind randomized comparison trial of paroxetine and mirtazapine. These two polymorphisms had previously been reported to predict efficacy in depressed patients treated with selective serotonin reuptake inhibitors such as paroxetine, and those treated with mirtazapine, an agent with both serotonergic and noradrenergic actions. However, we found no significant associations between these [[FKBP5]] genetic variants and clinical outcomes. Neither mean Hamilton Depression Rating Scale scores nor time to remission or response were predicted by [[FKBP5]] genetic variation. These results suggest that [[FKBP5]] is unlikely to play a major role in determining antidepressant treatment outcomes in geriatric patients.
|mesh-terms=* Aged
* Antidepressive Agents
* Depression
* Double-Blind Method
* Female
* Genetic Variation
* Geriatrics
* Humans
* Male
* Mianserin
* Mirtazapine
* Paroxetine
* Polymorphism, Genetic
* Sequence Analysis, DNA
* Tacrolimus Binding Proteins
* Treatment Outcome

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897151
}}

FKBP1B

2021-05-12T15:37:33Z

OdysseusBot: Новая страница: «Peptidyl-prolyl cis-trans isomerase FKBP1B (EC 5.2.1.8) (PPIase FKBP1B) (12.6 kDa FK506-binding protein) (12.6 kDa FKBP) (FKBP-12.6) (FK506-binding protein 1B) (F...»

Peptidyl-prolyl cis-trans isomerase FKBP1B (EC 5.2.1.8) (PPIase FKBP1B) (12.6 kDa FK506-binding protein) (12.6 kDa FKBP) (FKBP-12.6) (FK506-binding protein 1B) (FKBP-1B) (Immunophilin FKBP12.6) (Rotamase) (h-FKBP-12) [FKBP12.6] [FKBP1L] [FKBP9] [OTK4]

==Publications==

{{medline-entry
|title=The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32727592
|abstract=Periodontal ligament stem cells (PDLSCs) have many applications in the field of cytotherapy, tissue engineering, and regenerative medicine. However, the effect of age on the biological and immunological characteristics of PDLSCs remains unclear. In this study, we compared PDLSCs isolated from young and adult individuals. PDLSC proliferation was analyzed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining, and apoptosis level was detected by Annexin V-PE/7-ADD staining. PDLSC osteogenic/adipogenic/chondrogenic differentiation potentials were assessed by alkaline phosphatase (ALP), Alizarin Red, Oil Red O, Alcian Blue staining, and related quantitative analysis. PDLSC immunosuppressive capacity was determined by EdU and Annexin V-PE/7-ADD staining. To explore its underlying mechanism, microarray, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and western blot analyses were performed to detect differentially expressed genes and proteins in PDLSCs. Our results demonstrated that with aging, the proliferation and osteogenic/adipogenic/chondrogenic differentiation potential of PDLSCs decreased, whereas apoptosis of PDLSCs increased. Moreover, the immunosuppressive ability of PDLSCs decreased with aging. Compared with PDLSCs from young subjects, analysis of mRNA expression revealed an upregulation of [[CCND3]] and [[RC3H2]], and a downregulation of Runx2, ALP, [[COL1A1]], PPARγ2, [[CXCL12]], [[FKBP1A]], [[FKBP1B]], [[NCSTN]], [[P2RX7]], [[PPP3CB]], [[RIPK2]], [[SLC11A1]], and [[TP53]] in those from adult individuals. Furthermore, protein expression levels of Runx2, ALP, [[COL1A1]], and PPARγ2 in the adult group were decreased, whereas that of [[CCND3]] increased. Taken together, aging influences the biological and immunological characteristics of PDLSCs, and thus, it is more appropriate to utilize PDLSCs from young individuals for tissue regeneration, post-aging treatment, and allotransplantation.

|keywords=* Aging
* Immunosuppression
* Osteogenic differentiation
* Periodontal ligament stem cells
* Peripheral blood mononuclear cells
* Tissue engineering
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392710
}}

FKBP1A

2021-05-12T15:37:30Z

OdysseusBot: Новая страница: «Peptidyl-prolyl cis-trans isomerase FKBP1A (EC 5.2.1.8) (PPIase FKBP1A) (12 kDa FK506-binding protein) (12 kDa FKBP) (FKBP-12) (Calstabin-1) (FK506-binding protei...»

Peptidyl-prolyl cis-trans isomerase FKBP1A (EC 5.2.1.8) (PPIase FKBP1A) (12 kDa FK506-binding protein) (12 kDa FKBP) (FKBP-12) (Calstabin-1) (FK506-binding protein 1A) (FKBP-1A) (Immunophilin FKBP12) (Rotamase) [FKBP1] [FKBP12]

==Publications==

{{medline-entry
|title=The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32727592
|abstract=Periodontal ligament stem cells (PDLSCs) have many applications in the field of cytotherapy, tissue engineering, and regenerative medicine. However, the effect of age on the biological and immunological characteristics of PDLSCs remains unclear. In this study, we compared PDLSCs isolated from young and adult individuals. PDLSC proliferation was analyzed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining, and apoptosis level was detected by Annexin V-PE/7-ADD staining. PDLSC osteogenic/adipogenic/chondrogenic differentiation potentials were assessed by alkaline phosphatase (ALP), Alizarin Red, Oil Red O, Alcian Blue staining, and related quantitative analysis. PDLSC immunosuppressive capacity was determined by EdU and Annexin V-PE/7-ADD staining. To explore its underlying mechanism, microarray, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and western blot analyses were performed to detect differentially expressed genes and proteins in PDLSCs. Our results demonstrated that with aging, the proliferation and osteogenic/adipogenic/chondrogenic differentiation potential of PDLSCs decreased, whereas apoptosis of PDLSCs increased. Moreover, the immunosuppressive ability of PDLSCs decreased with aging. Compared with PDLSCs from young subjects, analysis of mRNA expression revealed an upregulation of [[CCND3]] and [[RC3H2]], and a downregulation of Runx2, ALP, [[COL1A1]], PPARγ2, [[CXCL12]], [[FKBP1A]], [[FKBP1B]], [[NCSTN]], [[P2RX7]], [[PPP3CB]], [[RIPK2]], [[SLC11A1]], and [[TP53]] in those from adult individuals. Furthermore, protein expression levels of Runx2, ALP, [[COL1A1]], and PPARγ2 in the adult group were decreased, whereas that of [[CCND3]] increased. Taken together, aging influences the biological and immunological characteristics of PDLSCs, and thus, it is more appropriate to utilize PDLSCs from young individuals for tissue regeneration, post-aging treatment, and allotransplantation.

|keywords=* Aging
* Immunosuppression
* Osteogenic differentiation
* Periodontal ligament stem cells
* Peripheral blood mononuclear cells
* Tissue engineering
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392710
}}

FIGNL1

2021-05-12T15:37:27Z

OdysseusBot: Новая страница: «Fidgetin-like protein 1 (EC 3.6.4.-) ==Publications== {{medline-entry |title=Comparative proteomic analysis of primordial follicles from ovaries of immature and...»

Fidgetin-like protein 1 (EC 3.6.4.-)

==Publications==

{{medline-entry
|title=Comparative proteomic analysis of primordial follicles from ovaries of immature and aged rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26391928
|abstract=Age related decline in reproductive performance in women is well documented and apoptosis has been considered as one of the reasons for the decline of primordial follicle reserve. Recently we observed a decline in the efficiency of DNA repair ability in aged rat primordial follicles as demonstrated by decreased mRNA levels of DNA repair genes [[BRCA1]] and [[H2AX]]. In the present study, a two-dimensional electrophoresis (2DE) proteomic approach was employed to identify differentially expressed proteins in primordial follicles isolated from ovaries of immature (∼20 days) and aged (∼400-450 days) rats. Using MALDI-TOF/TOF MS, we identified 13 differentially expressed proteins (p < 0.05) which included seven up-regulated and six down-regulated proteins in aged primordial follicles. These proteins are involved in a wide range of biological functions including apoptosis, DNA repair, and the immune system. Interestingly, the differentially expressed proteins such as [[FIGNL1]] (DNA repair) and [[BOK]] (apoptotic protein) have not been previously reported in the rat primordial follicles and these proteins can be related to some common features of ovarian aging such as loss of follicle reserve and genome integrity. The quantitative differences of two important proteins [[BOK]] and [[FIGNL1]] observed by the proteomic analysis were correlated with the transcript levels, as determined by semi-quantitative RT-PCR. Our results improve the current knowledge about protein factors associated with molecular changes in rat primordial follicles as a function of aging and our understanding of the proteomic processes involved in degenerative changes observed in aging primordial follicles.
|mesh-terms=* Aging
* Animals
* Electrophoresis, Gel, Two-Dimensional
* Female
* Ovarian Follicle
* Proteome
* Proteomics
* Rats
* Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
|keywords=* 2DE
* BOK
* Fignl1
* aging
* oocytes
* primordial follicles
|full-text-url=https://sci-hub.do/10.3109/19396368.2015.1077903
}}

FIG4

2021-05-12T15:37:25Z

OdysseusBot: Новая страница: «Polyphosphoinositide phosphatase (EC 3.1.3.-) (Phosphatidylinositol 3,5-bisphosphate 5-phosphatase) (SAC domain-containing protein 3) [KIAA0274] [SAC3] ==Publica...»

Polyphosphoinositide phosphatase (EC 3.1.3.-) (Phosphatidylinositol 3,5-bisphosphate 5-phosphatase) (SAC domain-containing protein 3) [KIAA0274] [SAC3]

==Publications==

{{medline-entry
|title=Knockdown of the Drosophila [[FIG4]] induces deficient locomotive behavior, shortening of motor neuron, axonal targeting aberration, reduction of life span and defects in eye development.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26708557
|abstract=Mutations in Factor-Induced-Gene 4 ([[FIG4]]) gene have been identified in Charcot-Marie-Tooth disease type 4J (CMT4J), Yunis-Varon syndrome and epilepsy with polymicrogyria. [[FIG4]] protein regulates a cellular abundance of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), a signaling lipid on the cytosolic surface of membranes of the late endosomal compartment. PI(3,5)P2 is required for retrograde membrane trafficking from lysosomal and late endosomal compartments to the Golgi. However, it is still unknown how the neurodegeneration that occurs in these diseases is related to the loss of [[FIG4]] function. Drosophila has CG17840 (d[[FIG4]]) as a human [[FIG4]] homolog. Here we specifically knocked down d[[FIG4]] in various tissues, and investigated their phenotypes. Neuron-specific knockdown of d[[FIG4]] resulted in axonal targeting aberrations of photoreceptor neurons, shortened presynaptic terminals of motor neurons in 3rd instar larvae and reduced climbing ability in adulthood and life span. Fat body-specific knockdown of d[[FIG4]] resulted in enlarged lysosomes in cells that were detected by staining with LysoTracker. In addition, eye imaginal disk-specific knockdown of d[[FIG4]] disrupted differentiation of pupal ommatidial cell types, such as cone cells and pigment cells, suggesting an additional role of d[[FIG4]] during eye development.
|mesh-terms=* Animals
* Animals, Genetically Modified
* Axons
* Central Nervous System
* Disease Models, Animal
* Drosophila
* Drosophila Proteins
* Eye Abnormalities
* Flavoproteins
* Gait Disorders, Neurologic
* Green Fluorescent Proteins
* Humans
* Imaginal Discs
* Longevity
* Lysosomes
* Motor Neurons
* Neuromuscular Junction
* Phosphoric Monoester Hydrolases
* Photoreceptor Cells, Invertebrate
* Psychomotor Disorders
* Sequence Alignment
|keywords=* CMT4J
* Drosophila
* Eye
* FIG4
* Neuron
|full-text-url=https://sci-hub.do/10.1016/j.expneurol.2015.12.011
}}

FHL2

2021-05-12T15:37:21Z

OdysseusBot: Новая страница: «Four and a half LIM domains protein 2 (FHL-2) (LIM domain protein DRAL) (Skeletal muscle LIM-protein 3) (SLIM-3) [DRAL] [SLIM3] ==Publications== {{medline-entry...»

Four and a half LIM domains protein 2 (FHL-2) (LIM domain protein DRAL) (Skeletal muscle LIM-protein 3) (SLIM-3) [DRAL] [SLIM3]

==Publications==

{{medline-entry
|title=Age prediction in living: Forensic epigenetic age estimation based on blood samples.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32721866
|abstract=DNA methylation analysis in a variety of genes has brought promising results in age estimation. The main aim of this study was to evaluate DNA methylation levels from four age-correlated genes, [[ELOVL2]], [[FHL2]], [[EDARADD]] and [[PDE4C]], in blood samples of healthy Portuguese individuals. Fifty-three samples were analyzed through the bisulfite polymerase chain reaction (PCR) sequencing method for CpG dinucleotide methylation status. Linear regression models were used to analyze relationships between methylation levels and chronological age. The highest age-associated CpG in each locus was chosen to build a multi-locus age prediction model (APM), allowing to obtain a Mean Absolute Deviation (MAD) between chronological and predicted ages of 5.35 years, explaining 94.1% of age variation. Validation approaches demonstrated the accuracy and reproducibility of the proposed multi-locus APM. Testing the APM in 51 blood samples from deceased individuals a MAD of 9.72 years was obtained. Potential differences in methylation status between samples from living and deceased individuals could exist since the highest age-correlated CpGs were different in some genes between both groups. In conclusion, our study using the bisulfite PCR sequencing method is in accordance with the high age prediction accuracy of DNA methylation levels in four previously reported age-associated genes. DNA methylation pattern differences between blood samples from living and deceased individuals should be taken into account in forensic contexts.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aging
* Child
* Child, Preschool
* CpG Islands
* Cyclic Nucleotide Phosphodiesterases, Type 4
* DNA Methylation
* Edar-Associated Death Domain Protein
* Fatty Acid Elongases
* Female
* Forensic Genetics
* Humans
* Infant
* LIM-Homeodomain Proteins
* Male
* Middle Aged
* Muscle Proteins
* Polymerase Chain Reaction
* Transcription Factors
* Young Adult
|keywords=* Age the living
* CpGs
* DNA methylation age
* Forensic epigenetics
* Forensic sciences
|full-text-url=https://sci-hub.do/10.1016/j.legalmed.2020.101763
}}
{{medline-entry
|title=Age Estimation Based on DNA Methylation Using Blood Samples From Deceased Individuals.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31490551
|abstract=Age estimation using DNA methylation levels has been widely investigated in recent years because of its potential application in forensic genetics. The main aim of this study was to develop an age predictor model (APM) for blood samples of deceased individuals based in five age-correlated genes. Fifty-one samples were analyzed through the bisulfite polymerase chain reaction (PCR) sequencing method for DNA methylation evaluation in genes [[ELOVL2]], [[FHL2]], [[EDARADD]], [[PDE4C]], and C1orf132. Linear regression was used to analyze relationships between methylation levels and age. The model using the highest age-correlated CpG from each locus revealed a correlation coefficient of 0.888, explaining 76.3% of age variation, with a mean absolute deviation from the chronological age (MAD) of 6.08 years. The model was validated in an independent test set of 19 samples producing a MAD of 8.84 years. The developed APM seems to be informative and could have potential application in forensic analysis.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* CpG Islands
* Cyclic Nucleotide Phosphodiesterases, Type 4
* DNA Methylation
* Edar-Associated Death Domain Protein
* Fatty Acid Elongases
* Female
* Forensic Genetics
* Genetic Markers
* Humans
* LIM-Homeodomain Proteins
* Linear Models
* Male
* Middle Aged
* Muscle Proteins
* Polymerase Chain Reaction
* Sequence Analysis, DNA
* Sulfites
* Transcription Factors
* Young Adult
|keywords=* DNA methylation age
* bisulfite PCR sequencing
* deceased individuals
* forensic epigenetics
* forensic science
|full-text-url=https://sci-hub.do/10.1111/1556-4029.14185
}}
{{medline-entry
|title=Genetic associations with age of menopause in familial longevity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31188284
|abstract=We hypothesize that mechanisms associated with extended reproductive age may overlap with mechanisms for the selection of genetic variants that slow aging and decrease risk for age-related diseases. Therefore, the goal of this analysis is to search for genetic variants associated with delayed age of menopause (AOM) among women in a study of familial longevity. We performed a meta-analysis of genome-wide association studies for AOM in 1,286 women in the Long Life Family Study (LLFS) and 3,151 women in the Health and Retirement Study, and then sought replication in the Framingham Heart Study (FHS). We used Cox proportional hazard regression of AOM to account for censoring, with a robust variance estimator to adjust for within familial relations. In the meta-analysis, a single nucleotide polymorphism (SNP) previously associated with AOM reached genome-wide significance (rs16991615; HR = 0.74, P = 6.99 × 10). A total of 35 variants reached >10 level of significance and replicated in the FHS and in a 2015 large meta-analysis (ReproGen Consortium). We also identified several novel SNPs associated with AOM including rs3094005: [[MICB]], rs13196892: [[TXNDC5]] | MUTED, rs72774935: [[SSBP2]] | [[ATG10]], rs9447453: [[COL12A1]], rs114298934: [[FHL2]] | [[NCK2]], rs6467223: [[TNPO3]], rs9666274 and rs10766593: [[NAV2]], and rs7281846: [[HSPA13]]. This work indicates novel associations and replicates known associations between genetic variants and AOM. A number of these associations make sense for their roles in aging. Supplemental Digital Content 1, http://links.lww.com/MENO/A420.
|mesh-terms=* Adult
* Age Factors
* Aged
* Aging
* Cohort Studies
* Family
* Female
* Genome, Human
* Genome-Wide Association Study
* Genotype
* Humans
* Longevity
* Male
* Menopause
* Middle Aged
* Polymorphism, Single Nucleotide
* Reproduction
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008937
}}
{{medline-entry
|title=DNA methylation of the [[ELOVL2]], [[FHL2]], [[KLF14]], C1orf132/MIR29B2C, and [[TRIM59]] genes for age prediction from blood, saliva, and buccal swab samples.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30300865
|abstract=Many studies have reported age-associated DNA methylation changes and age-predictive models in various tissues and body fluids. Although age-associated DNA methylation changes can be tissue-specific, a multi-tissue age predictor that is applicable to various tissues and body fluids with considerable prediction accuracy might be valuable. In this study, DNA methylation at 5 CpG sites from the [[ELOVL2]], [[FHL2]], [[KLF14]], C1orf132/MIR29B2C, and [[TRIM59]] genes were investigated in 448 samples from blood, saliva, and buccal swabs. A multiplex methylation SNaPshot assay was developed to measure DNA methylation simultaneously at the 5 CpG sites. Among the 5 CpG sites, 3 CpG sites in the [[ELOVL2]], [[KLF14]] and [[TRIM59]] genes demonstrated strong correlation between DNA methylation and age in all 3 sample types. Age prediction models built separately for each sample type using the DNA methylation values at the 5 CpG sites showed high prediction accuracy with a Mean Absolute Deviation from the chronological age (MAD) of 3.478 years in blood, 3.552 years in saliva and 4.293 years in buccal swab samples. A tissue-combined model constructed with 300 training samples including 100 samples from each blood, saliva and buccal swab samples demonstrated a very strong correlation between predicted and chronological ages (r = 0.937) and a high prediction accuracy with a MAD of 3.844 years in the 148 independent test set samples of 50 blood, 50 saliva and 48 buccal swab samples. Although more validation might be needed, the tissue-combined model's prediction accuracies in each sample type were very much similar to those obtained from each tissue-specific model. The multiplex methylation SNaPshot assay and the age prediction models in our study would be useful in forensic analysis, which frequently involves DNA from blood, saliva, and buccal swab samples.
|mesh-terms=* Acetyltransferases
* Adolescent
* Adult
* Aged
* Aging
* Blood Chemical Analysis
* CpG Islands
* DNA Methylation
* Fatty Acid Elongases
* Forensic Genetics
* Genetic Markers
* Genotyping Techniques
* Humans
* Intracellular Signaling Peptides and Proteins
* Kruppel-Like Transcription Factors
* LIM-Homeodomain Proteins
* Membrane Proteins
* Metalloproteins
* Middle Aged
* Mouth Mucosa
* Muscle Proteins
* Saliva
* Sequence Analysis, DNA
* Sp Transcription Factors
* Transcription Factors
* Tripartite Motif Proteins
* Young Adult
|keywords=* Age
* Blood
* Buccal swab
* DNA methylation
* Methylation SNaPshot
* Saliva
|full-text-url=https://sci-hub.do/10.1016/j.fsigen.2018.09.010
}}
{{medline-entry
|title=DNA methylation in [[ELOVL2]] and C1orf132 correctly predicted chronological age of individuals from three disease groups.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28725932
|abstract=Improving accuracy of the available predictive DNA methods is important for their wider use in routine forensic work. Information on age in the process of identification of an unknown individual may provide important hints that can speed up the process of investigation. DNA methylation markers have been demonstrated to provide accurate age estimation in forensics, but there is growing evidence that DNA methylation can be modified by various factors including diseases. We analyzed DNA methylation profile in five markers from five different genes ([[ELOVL2]], C1orf132, [[KLF14]], [[FHL2]], and [[TRIM59]]) used for forensic age prediction in three groups of individuals with diagnosed medical conditions. The obtained results showed that the selected age-related CpG sites have unchanged age prediction capacity in the group of late onset Alzheimer's disease patients. Aberrant hypermethylation and decreased prediction accuracy were found for [[TRIM59]] and [[KLF14]] markers in the group of early onset Alzheimer's disease suggesting accelerated aging of patients. In the Graves' disease patients, altered DNA methylation profile and modified age prediction accuracy were noted for [[TRIM59]] and [[FHL2]] with aberrant hypermethylation observed for the former and aberrant hypomethylation for the latter. Our work emphasizes high utility of the [[ELOVL2]] and C1orf132 markers for prediction of chronological age in forensics by showing unchanged prediction accuracy in individuals affected by three diseases. The study also demonstrates that artificial neural networks could be a convenient alternative for the forensic predictive DNA analyses.
|mesh-terms=* Acetyltransferases
* Adolescent
* Adult
* Aged
* Aging
* Alzheimer Disease
* Case-Control Studies
* Child
* Child, Preschool
* CpG Islands
* DNA Methylation
* Fatty Acid Elongases
* Female
* Forensic Genetics
* Genetic Markers
* Graves Disease
* Humans
* Intracellular Signaling Peptides and Proteins
* Kruppel-Like Transcription Factors
* LIM-Homeodomain Proteins
* Male
* Membrane Proteins
* Metalloproteins
* Middle Aged
* Multivariate Analysis
* Muscle Proteins
* Neural Networks, Computer
* Sp Transcription Factors
* Transcription Factors
* Tripartite Motif Proteins
* Young Adult
|keywords=* Alzheimer’s disease
* Chronological age
* DNA methylation
* Graves’ disease
* Neural networks
* Prediction accuracy
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748441
}}
{{medline-entry
|title=Independent validation of DNA-based approaches for age prediction in blood.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28511095
|abstract=Numerous molecular biomarkers have been proposed as predictors of chronological age. Among them, T-cell specific DNA rearrangement and DNA methylation markers have been introduced as forensic age predictors in blood because of their high prediction accuracy. These markers appear highly promising, but for better application to forensic casework sample analysis the proposed markers and genotyping methods must be tested further. In the current study, signal-joint T-cell receptor excision circles (sjTRECs) and DNA methylation markers located in the [[ELOVL2]], C1orf132, [[TRIM59]], [[KLF14]], and [[FHL2]] genes were reanalyzed in 100 Korean blood samples to test their associations with chronological age, using the same analysis platform used in previous reports. Our study replicated the age association test for sjTREC and DNA methylation markers in the 5 genes in an independent validation set of 100 Koreans, and proved that the age predictive performance of the previous models is relatively consistent across different population groups. However, the extent of age association at certain CpG loci was not identical in the Korean and Polish populations; therefore, several age predictive models were retrained with the data obtained here. All of the 3 models retrained with DNA methylation and/or sjTREC data have a CpG site each from the [[ELOVL2]] and [[FHL2]] genes in common, and produced better prediction accuracy than previously reported models. This is attributable to the fact that the retrained model better fits the existing data and that the calculated prediction accuracy could be higher when the training data and the test data are the same. However, it is notable that the combination of different types of markers, i.e., sjTREC and DNA methylation, improved prediction accuracy in the eldest group. Our study demonstrates the usefulness of the proposed markers and the genotyping method in an independent dataset, and suggests the possibility of combining different types of DNA markers to improve prediction accuracy.
|mesh-terms=* Acetyltransferases
* Aging
* Asian Continental Ancestry Group
* CpG Islands
* DNA Methylation
* Fatty Acid Elongases
* Genetic Markers
* Genotyping Techniques
* Humans
* Intracellular Signaling Peptides and Proteins
* Kruppel-Like Transcription Factors
* LIM-Homeodomain Proteins
* Membrane Proteins
* Metalloproteins
* Muscle Proteins
* Receptors, Antigen, T-Cell
* Republic of Korea
* Sp Transcription Factors
* Transcription Factors
* Tripartite Motif Proteins
|keywords=* Age prediction
* Blood
* DNA methylation
* Forensic science
* Korean
* sjTREC
|full-text-url=https://sci-hub.do/10.1016/j.fsigen.2017.04.020
}}
{{medline-entry
|title=Genome-wide DNA methylation analysis reveals hypomethylation in the low-CpG promoter regions in lymphoblastoid cell lines.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28499412
|abstract=Epidemiological studies of DNA methylation profiles may uncover the molecular mechanisms through which genetic and environmental factors contribute to the risk of multifactorial diseases. There are two types of commonly used DNA bioresources, peripheral blood cells (PBCs) and EBV-transformed lymphoblastoid cell lines (LCLs), which are available for genetic epidemiological studies. Therefore, to extend our knowledge of the difference in DNA methylation status between LCLs and PBCs is important in human population studies that use these DNA sources to elucidate the epigenetic risks for multifactorial diseases. We analyzed the methylation status of the autosomes for 192 and 92 DNA samples that were obtained from PBCs and LCLs, respectively, using a human methylation 450 K array. After excluding SNP-associated methylation sites and low-call sites, 400,240 sites were subjected to analysis using a generalized linear model with cell type, sex, and age as the independent variables. We found that the large proportion of sites showed lower methylation levels in LCLs compared with PBCs, which is consistent with previous reports. We also found that significantly different methylation sites tend to be located on the outside of the CpG island and in a region relatively far from the transcription start site. Additionally, we observed that the methylation change of the sites in the low-CpG promoter region was remarkable. Finally, it was shown that the correlation between the chronological age and ageing-associated methylation sites in [[ELOVL2]] and [[FHL2]] in the LCLs was weaker than that in the PBCs. The methylation levels of highly methylated sites of the low-CpG-density promoters in PBCs decreased in the LCLs, suggesting that the methylation sites located in low-CpG-density promoters could be sensitive to demethylation in LCLs. Despite being generated from a single cell type, LCLs may not always be a proxy for DNA from PBCs in studies of epigenome-wide analysis attempting to elucidate the role of epigenetic change in disease risks.
|mesh-terms=* Acetyltransferases
* Aging
* Blood Cells
* Cell Line, Transformed
* CpG Islands
* DNA Methylation
* Fatty Acid Elongases
* Genome-Wide Association Study
* Humans
* LIM-Homeodomain Proteins
* Lymphocyte Activation
* Muscle Proteins
* Transcription Factors
|keywords=* DNA methylation
* Epigenetic epidemiology
* Epigenome-wide analysis
* Human methylation array
* Lymphoblastoid cell lines
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429538
}}
{{medline-entry
|title=Systemic Age-Associated DNA Hypermethylation of [[ELOVL2]] Gene: In Vivo and In Vitro Evidences of a Cell Replication Process.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27672102
|abstract=Epigenetic remodeling is one of the major features of the aging process. We recently demonstrated that DNA methylation of [[ELOVL2]] and [[FHL2]] CpG islands is highly correlated with age in whole blood. Here we investigated several aspects of age-associated hypermethylation of [[ELOVL2]] and [[FHL2]]. We showed that [[ELOVL2]] methylation is significantly different in primary dermal fibroblast cultures from donors of different ages. Using epigenomic data from public resources, we demonstrated that most of the tissues show [[ELOVL2]] and [[FHL2]] hypermethylation with age. Interestingly, [[ELOVL2]] hypermethylation was not found in tissues with very low replication rate. We demonstrated that [[ELOVL2]] hypermethylation is associated with in vitro cell replication rather than with senescence. We confirmed intra-individual hypermethylation of [[ELOVL2]] and [[FHL2]] in longitudinally assessed participants from the Doetinchem Cohort Study. Finally we showed that, although the methylation of the two loci is not associated with longevity/mortality in the Leiden Longevity Study, [[ELOVL2]] methylation is associated with cytomegalovirus status in nonagenarians, which could be informative of a higher number of replication events in a fraction of whole-blood cells. Collectively, these results indicate that [[ELOVL2]] methylation is a marker of cell divisions occurring during human aging.
|mesh-terms=* Acetyltransferases
* Aged
* Aging
* Cell Proliferation
* Cells, Cultured
* Cellular Senescence
* CpG Islands
* DNA Methylation
* Epigenesis, Genetic
* Fatty Acid Elongases
* Female
* Humans
* LIM-Homeodomain Proteins
* Longevity
* Longitudinal Studies
* Male
* Middle Aged
* Muscle Proteins
* Transcription Factors
|keywords=* Biomarker
* Epigenetics
* FHL2
* Methylation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861890
}}
{{medline-entry
|title=Donor age and C1orf132/MIR29B2C determine age-related methylation signature of blood after allogeneic hematopoietic stem cell transplantation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27602173
|abstract=Our recent study demonstrated that DNA methylation status in a set of CpGs located in [[ELOVL2]], C1orf132, [[TRIM59]], [[KLF14]], and [[FHL2]] can accurately predict calendar age in blood. In the present work, we used these markers to evaluate the effect of allogeneic hematopoietic stem cell transplantation (HSCT) on the age-related methylation signature of human blood. DNA methylation in 32 CpGs was investigated in 16 donor-recipient pairs using pyrosequencing. DNA was isolated from the whole blood collected from recipients 27-360 days (mean 126) after HSCT and from the donors shortly before the HSCT. It was found that in the recipients, the predicted age did not correlate with their calendar age but was correlated with the calendar age (r = 0.94, p = 4 × 10(-8)) and predicted age (r = 0.97, p = 5 × 10(-10)) of a respective donor. Despite this strong correlation, the predicted age of a recipient was consistently lower than the predicted age of a donor by 3.7 years (p = 7.8 × 10(-4)). This shift was caused by hypermethylation of the C1orf132 CpGs, for C1orf132 CpG_1. Intriguingly, the recipient-donor methylation difference correlated with calendar age of the donor (r = 0.76, p = 6 × 10(-4)). This finding could not trivially be explained by shifts of the major cellular factions of blood. We confirm the single previous report that after HSCT, the age of the donor is the major determinant of age-specific methylation signature in recipient's blood. A novel finding is the unique methylation dynamics of C1orf132 which encodes MIR29B2C implicated in the self-renewing of hematopoietic stem cells. This observation suggests that C1orf132 could influence graft function after HSCT.
|mesh-terms=* DNA Methylation
* Hematopoietic Stem Cell Transplantation
* Humans
* Tissue Donors
|keywords=* Aging
* Allogeneic hematopoietic stem cell transplantation
* DNA methylation
* MIR29B2C
* Rejuvenation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012039
}}
{{medline-entry
|title=Forensic age prediction for dead or living samples by use of methylation-sensitive high resolution melting.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27497326
|abstract=Age prediction with epigenetic information is now edging closer to practical use in forensic community. Many age-related CpG (AR-CpG) sites have proven useful in predicting age in pyrosequencing or DNA chip analyses. In this study, a wide range methylation status in the [[ELOVL2]] and [[FHL2]] promoter regions were detected with methylation-sensitive high resolution melting (MS-HRM) in a labor-, time-, and cost-effective manner. Non-linear-distributions of methylation status and chronological age were newly fitted to the logistic curve. Notably, these distributions were revealed to be similar in 22 living blood samples and 52 dead blood samples. Therefore, the difference of methylation status between living and dead samples suggested to be ignorable by MS-HRM. Additionally, the information from [[ELOVL2]] and [[FHL2]] were integrated into a logistic curve fitting model to develop a final predictive model through the multivariate linear regression of logit-linked methylation rates and chronological age with adjusted R(2)=0.83. Mean absolute deviation (MAD) was 7.44 for 74 training set and 7.71 for 30 additional independent test set, indicating that the final predicting model is accurate. This suggests that our MS-HRM-based method has great potential in predicting actual forensic age.
|mesh-terms=* Age Determination by Skeleton
* Aging
* DNA Methylation
* Forensic Anthropology
* Forensic Genetics
* Polymerase Chain Reaction
|keywords=* Age prediction
* DNA methylation
* Forensic science
* MS-HRM
|full-text-url=https://sci-hub.do/10.1016/j.legalmed.2016.05.001
}}
{{medline-entry
|title=Identification of common and differential mechanisms of glomerulus and tubule senescence in 24-month-old rats by quantitative LC-MS/MS.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27452873
|abstract=Kidney aging together with related renal disease had become a major clinical problem. Understanding the mechanisms of aging was important for suspending senescence and decreasing the incidence of aging-related diseases. In the present work, 24-month-old F344 rats were used as aging rats and 3-month-old rats were used as young controls. Senescence-associated-β-galactosidase staining results showed that the degree of senescence in renal tubules was more severe than that in glomeruli. We performed quantitative LC-MS to assess the differential protein expression profiles of senescent glomeruli and tubules. Bioinformatics analysis showed that aging, response to oxidative stress, nucleotide metabolism, amine acid metabolism, and inflammatory response were common mechanisms of glomerulus and tubule senescence. Differentially expressed proteins network mediated Golgi vesicle transport, actin filament based process, and regulation of cell death were associated with tubule senescence. More importantly, we found that the changes of four and a half LIM protein 2 ([[FHL2]]) were opposite in senescent glomeruli and tubules, and [[FHL2]] could regulate p16 by suppressing T-box 3, which was involved in regulation of senescence in glomeruli and tubules. In conclusion, we assessed the mechanisms of senescence in aging glomeruli and tubules, and the results yielded new insight into kidney senescence.
|mesh-terms=* Actin Cytoskeleton
* Aging
* Animals
* Cell Line
* Cellular Senescence
* Chromatography, Liquid
* Cyclin-Dependent Kinase Inhibitor p16
* Kidney Glomerulus
* Kidney Tubules
* LIM-Homeodomain Proteins
* Muscle Proteins
* Oxidative Stress
* Proteome
* Proteomics
* Rats, Inbred F344
* T-Box Domain Proteins
* Tandem Mass Spectrometry
* Transcription Factors
|keywords=* Aging
* Animal proteomics
* FHL2
* Glomerular
* Tubule
|full-text-url=https://sci-hub.do/10.1002/pmic.201600121
}}
{{medline-entry
|title=Development of a methylation marker set for forensic age estimation using analysis of public methylation data and the Agena Bioscience EpiTYPER system.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27337627
|abstract=Individual age estimation has the potential to provide key information that could enhance and extend DNA intelligence tools. Following predictive tests for externally visible characteristics developed in recent years, prediction of age could guide police investigations and improve the assessment of age-related phenotype expression patterns such as hair colour changes and early onset of male pattern baldness. DNA methylation at CpG positions has emerged as the most promising DNA tests to ascertain the individual age of the donor of a biological contact trace. Although different methodologies are available to detect DNA methylation, EpiTYPER technology (Agena Bioscience, formerly Sequenom) provides useful characteristics that can be applied as a discovery tool in localized regions of the genome. In our study, a total of twenty-two candidate genomic regions, selected from the assessment of publically available data from the Illumina HumanMethylation 450 BeadChip, had a total of 177 CpG sites with informative methylation patterns that were subsequently investigated in detail. From the methylation analyses made, a novel age prediction model based on a multivariate quantile regression analysis was built using the seven highest age-correlated loci of [[ELOVL2]], [[ASPA]], [[PDE4C]], [[FHL2]], [[CCDC102B]], C1orf132 and chr16:85395429. The detected methylation levels in these loci provide a median absolute age prediction error of ±3.07years and a percentage of prediction error relative to the age of 6.3%. We report the predictive performance of the developed model using cross validation of a carefully age-graded training set of 725 European individuals and a test set of 52 monozygotic twin pairs. The multivariate quantile regression age predictor, using the CpG sites selected in this study, has been placed in the open-access Snipper forensic classification website.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* CpG Islands
* DNA Methylation
* Female
* Genetic Loci
* Genetic Markers
* Humans
* Male
* Mass Spectrometry
* Middle Aged
* Multivariate Analysis
* Polymerase Chain Reaction
* Software
* Twins, Monozygotic
* Young Adult
|keywords=* Agena Bioscience EpiTYPER
* CpG sites
* DNA methylation
* Forensic age estimation
* Illumina HumanMethylation 450K
* Multivariate quantile regression
|full-text-url=https://sci-hub.do/10.1016/j.fsigen.2016.06.005
}}
{{medline-entry
|title=Aging-associated DNA methylation changes in middle-aged individuals: the Young Finns study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26861258
|abstract=Chronological aging-associated changes in the human DNA methylome have been studied by multiple epigenome-wide association studies (EWASs). Certain CpG sites have been identified as aging-associated in multiple studies, and the majority of the sites identified in various studies show common features regarding location and direction of the methylation change. However, as a whole, the sets of aging-associated CpGs identified in different studies, even with similar tissues and age ranges, show only limited overlap. In this study, we further explore and characterize CpG sites that show close relationship between their DNA methylation level and chronological age during adulthood and which bear the relationship regardless of blood cell type heterogeneity. In this study, with a multivariable regression model adjusted for cell type heterogeneity, we identified 1202 aging-associated CpG sites (a-CpGs, FDR < 5%), in whole blood in a population with an especially narrow age range (40 - 49 years). Repeatedly reported a-CpGs located in genes [[ELOVL2]], [[FHL2]], [[PENK]] and [[KLF14]] were also identified. Regions with aging-associated hypermethylation were enriched regarding several gene ontology (GO) terms (especially in the cluster of developmental processes), whereas hypomethylated sites showed no enrichment. The genes with higher numbers of a-CpG hits were more often hypermethylated with advancing age. The comparison analysis revealed that of the 1202 a-CpGs identified in the present study, 987 were identified as differentially methylated also between nonagenarians and young adults in a previous study (The Vitality 90 study), and importantly, the directions of changes were identical in the previous and in the present study. Here we report that aging-associated DNA methylation features can be identified in a middle-aged population with an age range of only 9 years. A great majority of these sites have been previously reported as aging-associated in a population aged 19 to 90 years. Aging is associated with different types of changes in DNA methylation, clock-like as well as random. We speculate that the a-CpGs identified here in a population with a narrow age-range represent clock-like changes, as they showed concordant methylation behavior in population spanning whole adulthood as well.
|mesh-terms=* Adult
* Age Factors
* Aging
* CpG Islands
* DNA Methylation
* Epigenesis, Genetic
* Epigenomics
* Female
* Genome, Human
* Genome-Wide Association Study
* Humans
* Male
* Middle Aged
* Sex Factors

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746895
}}
{{medline-entry
|title=Development of a forensically useful age prediction method based on DNA methylation analysis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26026729
|abstract=Forensic DNA phenotyping needs to be supplemented with age prediction to become a relevant source of information on human appearance. Recent progress in analysis of the human methylome has enabled selection of multiple candidate loci showing linear correlation with chronological age. Practical application in forensic science depends on successful validation of these potential age predictors. In this study, eight DNA methylation candidate loci were analysed using convenient and reliable pyrosequencing technology. A total number of 41 CpG sites was investigated in 420 samples collected from men and women aged from 2 to 75 years. The study confirmed correlation of all the investigated markers with human age. The five most significantly correlated CpG sites in [[ELOVL2]] on 6p24.2, C1orf132 on 1q32.2, [[TRIM59]] on 3q25.33, [[KLF14]] on 7q32.3 and [[FHL2]] on 2q12.2 were chosen to build a prediction model. This restriction allowed the technical analysis to be simplified without lowering the prediction accuracy significantly. Model parameters for a discovery set of 300 samples were R(2)=0.94 and the standard error of the estimate=4.5 years. An independent set of 120 samples was used to test the model performance. Mean absolute deviation for this testing set was 3.9 years. The number of correct predictions ±5 years achieved a very high level of 86.7% in the age category 2-19 and gradually decreased to 50% in the age category 60-75. The prediction model was deterministic for individuals belonging to these two extreme age categories. The developed method was implemented in a freely available online age prediction calculator.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aging
* Child
* Child, Preschool
* CpG Islands
* DNA
* DNA Methylation
* Female
* Forensic Genetics
* Humans
* Male
* Middle Aged
* Predictive Value of Tests
|keywords=* DNA methylation
* DNA-based age prediction
* Forensic science
* Prediction modelling
|full-text-url=https://sci-hub.do/10.1016/j.fsigen.2015.05.001
}}
{{medline-entry
|title=Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24789080
|abstract=Aging is a progressive process that results in the accumulation of intra- and extracellular alterations that in turn contribute to a reduction in health. Age-related changes in DNA methylation have been reported before and may be responsible for aging-induced changes in gene expression, although a causal relationship has yet to be shown. Using genome-wide assays, we analyzed age-induced changes in DNA methylation and their effect on gene expression with and without transient induction with the synthetic transcription modulating agent WY14,643. To demonstrate feasibility of the approach, we isolated peripheral blood mononucleated cells (PBMCs) from five young and five old healthy male volunteers and cultured them with or without WY14,643. Infinium 450K BeadChip and Affymetrix Human Gene 1.1 ST expression array analysis revealed significant differential methylation of at least 5 % (ΔYO > 5 %) at 10,625 CpG sites between young and old subjects, but only a subset of the associated genes were also differentially expressed. Age-related differential methylation of previously reported epigenetic biomarkers of aging including [[ELOVL2]], [[FHL2]], [[PENK]], and [[KLF14]] was confirmed in our study, but these genes did not display an age-related change in gene expression in PBMCs. Bioinformatic analysis revealed that differentially methylated genes that lack an age-related expression change predominantly represent genes involved in carcinogenesis and developmental processes, and expression of most of these genes were silenced in PBMCs. No changes in DNA methylation were found in genes displaying transiently induced changes in gene expression. In conclusion, aging-induced differential methylation often targets developmental genes and occurs mostly without change in gene expression.
|mesh-terms=* Adult
* Aged
* Aging
* Cells, Cultured
* DNA Methylation
* Epigenesis, Genetic
* Gene Expression Regulation, Developmental
* Genome, Human
* Healthy Volunteers
* Humans
* Leukocytes, Mononuclear
* Male
* Middle Aged
* RNA

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082572
}}
{{medline-entry
|title=Methylation of [[ELOVL2]] gene as a new epigenetic marker of age.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23061750
|abstract=The discovery of biomarkers able to predict biological age of individuals is a crucial goal in aging research. Recently, researchers' attention has turn toward epigenetic markers of aging. Using the Illumina Infinium HumanMethylation450 BeadChip on whole blood DNA from a small cohort of 64 subjects of different ages, we identified 3 regions, the CpG islands of [[ELOVL2]], [[FHL2]], and [[PENK]] genes, whose methylation level strongly correlates with age. These results were confirmed by the Sequenom's EpiTYPER assay on a larger cohort of 501 subjects from 9 to 99 years, including 7 cord blood samples. Among the 3 genes, [[ELOVL2]] shows a progressive increase in methylation that begins since the very first stage of life (Spearman's correlation coefficient = 0.92) and appears to be a very promising biomarker of aging.
|mesh-terms=* Acetyltransferases
* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Child
* CpG Islands
* DNA Methylation
* Enkephalins
* Epigenesis, Genetic
* Fatty Acid Elongases
* Female
* Fetal Blood
* Genetic Markers
* Genome, Human
* Humans
* LIM-Homeodomain Proteins
* Male
* Middle Aged
* Muscle Proteins
* Oligonucleotide Array Sequence Analysis
* Protein Precursors
* Transcription Factors

|full-text-url=https://sci-hub.do/10.1111/acel.12005
}}
{{medline-entry
|title=Developmental evolution of the delayed rectifier current IKs in canine heart appears dependent on the beta subunit minK.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15851242
|abstract=We tested the hypothesis that the developmental changes occurring in I(Kr) and I(Ks) can be explained by changes in the expression of [[ERG]] encoding I(Kr), and [[KCNQ1]], the beta subunit minK, and the recently reported subunit [[FHL2]] encoding I(Ks). The delayed rectifier current contributes importantly to the developmental evolution of the canine myocardial action potential. Specifically, in left ventricular epicardial myocytes, I(Ks) is absent and I(Kr) is the major repolarizing current until age 4 weeks. With subsequent development, I(Ks) density increases and I(Kr) decreases, resulting in an altered voltage-time course of repolarization. We used Western blotting and real-time polymerase chain reaction to compare the expression of [[ERG]], [[KCNQ1]], minK, and [[FHL2]] in 1-week-old pups and adult dogs. [[ERG]] levels are high at 1 week and decrease significantly with age, consistent with developmental decrease in I(Kr). Whereas expression of [[KCNQ1]] and [[FHL2]] is unchanged between the two age groups, minK is minimally expressed at 1 week and increases in adults, consistent with developmental increase in I(Ks). A reduction in [[ERG]] explains the developmental decrease in I(Kr), whereas the accessory subunit minK appears to be the critical determinant of developmental evolution of I(Ks).
|mesh-terms=* Aging
* Animals
* Blotting, Western
* Cation Transport Proteins
* Dogs
* Ether-A-Go-Go Potassium Channels
* Female
* Heart Ventricles
* Male
* Myocytes, Cardiac
* Pericardium
* Polymerase Chain Reaction
* Potassium Channels, Voltage-Gated
* RNA, Messenger

|full-text-url=https://sci-hub.do/10.1016/j.hrthm.2004.08.012
}}

FH

2021-05-12T15:37:18Z

OdysseusBot: Новая страница: «Fumarate hydratase, mitochondrial precursor (EC 4.2.1.2) (Fumarase) (HsFH) ==Publications== {{medline-entry |title=Genetic Factors of Alzheimer's Disease Modula...»

Fumarate hydratase, mitochondrial precursor (EC 4.2.1.2) (Fumarase) (HsFH)

==Publications==

{{medline-entry
|title=Genetic Factors of Alzheimer's Disease Modulate How Diet is Associated with Long-Term Cognitive Trajectories: A UK Biobank Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33252089
|abstract=Fluid intelligence (FI) involves abstract problem-solving without prior knowledge. Greater age-related FI decline increases Alzheimer's disease (AD) risk, and recent studies suggest that certain dietary regimens may influence rates of decline. However, it is uncertain how long-term food consumption affects FI among adults with or without familial history of AD ([[FH]]) or APOE4 (ɛ4). Observe how the total diet is associated with long-term cognition among mid- to late-life populations at-risk and not-at-risk for AD. Among 1,787 mid-to-late-aged adult UK Biobank participants, 10-year FI trajectories were modeled and regressed onto the total diet based on self-reported intake of 49 whole foods from a Food Frequency Questionnaire (FFQ). Daily cheese intake strongly predicted better FIT scores over time ([[FH]]-: β= 0.207, p < 0.001; ɛ4-: β= 0.073, p = 0.008; ɛ4 : β= 0.162, p = 0.001). Alcohol of any type daily also appeared beneficial (ɛ4 : β= 0.101, p = 0.022) and red wine was sometimes additionally protective ([[FH]] : β= 0.100, p = 0.014; ɛ4-: β= 0.59, p = 0.039). Consuming lamb weekly was associated with improved outcomes ([[FH]]-: β= 0.066, p = 0.008; ɛ4 : β= 0.097, p = 0.044). Among at risk groups, added salt correlated with decreased performance ([[FH]] : β= -0.114, p = 0.004; ɛ4 : β= -0.121, p = 0.009). Modifying meal plans may help minimize cognitive decline. We observed that added salt may put at-risk individuals at greater risk, but did not observe similar interactions among [[FH]]- and AD- individuals. Observations further suggest in risk status-dependent manners that adding cheese and red wine to the diet daily, and lamb on a weekly basis, may also improve long-term cognitive outcomes.

|keywords=* APOE4
* Aging
* Mediterranean diet
* cognitive decline
* functional food
* lamb
* nutrition policy
* preventive medicine
* red wine
* salt
|full-text-url=https://sci-hub.do/10.3233/JAD-201058
}}
{{medline-entry
|title=Genetic risk of dementia modifies obesity effects on white matter myelin in cognitively healthy adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32736120
|abstract=[[APOE]]-ε4 is a major genetic risk factor for late-onset Alzheimer's disease that interacts with other risk factors, but the nature of such combined effects remains poorly understood. We quantified the impact of [[APOE]]-ε4, family history ([[FH]]) of dementia, and obesity on white matter (WM) microstructure in 165 asymptomatic adults (38-71 years old) using quantitative magnetization transfer and neurite orientation dispersion and density imaging. Microstructural properties of the fornix, parahippocampal cingulum, and uncinate fasciculus were compared with those in motor and whole-brain WM regions. Widespread interaction effects between [[APOE]], [[FH]], and waist-hip ratio were found in the myelin-sensitive macromolecular proton fraction from quantitative magnetization transfer. Among individuals with the highest genetic risk ([[FH]] and [[APOE]]-ε4), obesity was associated with reduced macromolecular proton fraction in the right parahippocampal cingulum, whereas no effects were present for those without [[FH]]. Risk effects on apparent myelin were moderated by hypertension and inflammation-related markers. These findings suggest that genetic risk modifies the impact of obesity on WM myelin consistent with neuroglia models of aging and late-onset Alzheimer's disease.

|keywords=* APOE
* Aging
* Alzheimer’s disease
* Central obesity
* Family history of dementia
* Hypertension
* Inflammation
* Myelin
* Parahippocampal cingulum
|full-text-url=https://sci-hub.do/10.1016/j.neurobiolaging.2020.06.014
}}
{{medline-entry
|title=Volumetric alterations in the hippocampal subfields of subjects at increased risk of dementia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32311609
|abstract=The hippocampus is one of the first regions to demonstrate atrophy during the prodromal stage of Alzheimer's disease. Volumetric analysis of its individual subfields could provide biomarkers with higher sensitivity than whole hippocampal volume during an earlier disease stage. We quantified the hippocampal subfields volume in a large cohort comprising healthy participants (aged 40-59) with dementia family history ([[FH]]) and controls (without [[FH]]), examined at 2 time points across 2 years. Subfield volumes were quantified using both a T1-weighted and a high-resolution T2 hippocampal magnetic resonance imaging acquisition with Freesurfer. The participants were stratified based on dementia [[FH]], [[APOE]] genotype, and CAIDE (Cardiovascular Risk Factors, Aging and Dementia) risk score. Whole hippocampal volume did not differ between the groups. The volume of the molecular layer was lower in participants with an [[APOE]] ε4 genotype, but there were no differences between subjects with and without dementia [[FH]] or with an increasing CAIDE score. The molecular layer may be the first hippocampal region to demonstrate volumetric alterations in subjects at risk of dementia.
|mesh-terms=* Adult
* Aging
* Alzheimer Disease
* Apolipoproteins E
* Atrophy
* Dementia
* Diffusion Magnetic Resonance Imaging
* Educational Status
* Female
* Genotype
* Hippocampus
* Humans
* Male
* Middle Aged
* Organ Size
* Risk
|keywords=* Alzheimer's disease
* Dementia
* Hippocampal subfields
* Hippocampus
* Preclinical dementia
|full-text-url=https://sci-hub.do/10.1016/j.neurobiolaging.2020.03.006
}}
{{medline-entry
|title=Macroscopic hematuria as a risk factor for hypertension in ageing people with hemophilia and a family history of hypertension.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32118768
|abstract=Ageing people with hemophilia (PWH) have a higher prevalence of hypertension than the general population. This study aimed to determine whether macroscopic hematuria was associated with hypertension in PWH in a post hoc analysis using data from a cross-sectional study conducted by the ADVANCE Working Group (the H3 study), which included PWH ≥ 40 years of age. Data from 16 contributing centers, located in 13 European countries and Israel, were analyzed using logistic regression models. Of 532 recruited PWH in the H3 study, 117 had hypertension and a positive family history of hypertension (hypertension [[FH]] ), 75 had hypertension and a negative family history of hypertension (hypertension [[FH]]-), 290 had no diagnosis of hypertension, and the remaining 50 had missing hypertension data. Logistic regressions showed that macroscopic hematuria was associated with hypertension [[FH]] , both in the univariate (OR = 1.84 [1.17-2.90], P = .01) and in the multivariate model (OR = 1.80 [1.03-3.16], P = .04). Macroscopic hematuria was not associated with hypertension [[FH]]-. Moreover, in a multivariate logistic regression the odds of hypertension [[FH]] were increased with the number of macroscopic hematuria episodes. The association between macroscopic hematuria and hypertension was significant for PWH with a family history of hypertension.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Cross-Sectional Studies
* Female
* Hematuria
* Hemophilia A
* Humans
* Hypertension
* Israel
* Logistic Models
* Male
* Middle Aged
* Risk Factors

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478422
}}
{{medline-entry
|title=LDL Receptor Deficiency Does not Alter Brain Amyloid-β Levels but Causes an Exacerbation of Apoptosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31815695
|abstract=Familial hypercholesterolemia ([[FH]]) is a genetic disorder caused by dysfunction of low density lipoprotein receptors (LDLr), resulting in elevated plasma cholesterol levels. [[FH]] patients frequently exhibit cognitive impairment, a finding recapitulated in LDLr deficient mice (LDLr-/-), an animal model of [[FH]]. In addition, LDLr-/- mice are more vulnerable to the deleterious memory impact of amyloid-β (Aβ), a peptide linked to Alzheimer's disease. Here, we investigated whether the expression of proteins involved in Aβ metabolism are altered in the brains of adult or middle-aged LDLr-/- mice. After spatial memory assessment, Aβ levels and gene expression of LDLr related-protein 1, proteins involved in Aβ synthesis, and apoptosis-related proteins were evaluated in prefrontal cortex and hippocampus. Moreover, the location and cell-specificity of apoptosis signals were evaluated. LDLr-/- mice presented memory impairment, which was more severe in middle-aged animals. Memory deficit in LDLr-/- mice was not associated with altered expression of proteins involved in Aβ processing or changes in Aβ levels in either hippocampus or prefrontal cortex. We further found that the expression of Bcl-2 was reduced while the expression of Bax was increased in both prefrontal cortex and hippocampus in 3- and 14-month-old LDLr-/-mice Finally, LDLr-/- mice presented increased immunoreactivity for activated caspase-3 in the prefrontal cortex and hippocampus. The activation of caspase 3 was predominantly associated with neurons in LDLr-/- mice. Cognitive impairment in LDLr-/- mice is thus accompanied by an exacerbation of neuronal apoptosis in brain regions related to memory formation, but not by changes in Aβ processing or levels.
|mesh-terms=* Aging
* Amyloid beta-Protein Precursor
* Animals
* Apoptosis
* Brain Chemistry
* Caspase 3
* Cholesterol
* Gene Expression
* Hippocampus
* Male
* Maze Learning
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Prefrontal Cortex
* Receptors, LDL
|keywords=* Familial hypercholesterolemia
* LDLr-/- mice
* amyloid-β
* apoptosis
* memory impairment
|full-text-url=https://sci-hub.do/10.3233/JAD-190742
}}
{{medline-entry
|title=Sex differences in cholesterol levels from birth to 19 years of age may lead to increased cholesterol burden in females with [[FH]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29609857
|abstract=The increased risk of cardiovascular disease in familial hypercholesterolemia ([[FH]]) is caused by increased cholesterol burden from birth. Even small elevation in cholesterol level accumulates over time and aggravates atherosclerosis. The aim of the present study was to describe the lipid profile across sex and age in a large cohort of untreated children and adolescents with [[FH]], as this have not clearly been described. [[FH]] children (438 girls, 452 boys) not receiving lipid-lowering therapy, aged 0 to 19 years were included and divided into 4 age groups (<5, 5-9, 10-14, and 15-19 years). Information was retrieved from the medical records. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and non-HDL cholesterol (non-HDL-C) were studied in relation to sex and age by multiple linear regression analysis. Girls with [[FH]] as compared to boys had significantly higher TC, LDL-C, and non-HDL-C (P < .001 for all) levels with mean (95% confidence interval) differences of 0.48 mmol/L (0.28, 0.68) (18.6 g/dL), 0.39 mmol/L (0.19, 0.59) (15.08 mg/dL), and 0.42 mmol/L (0.22, 0.63) (16.24 mg/dL), respectively. These estimates did not change after adjustment for age. We also observed sex differences for HDL-C; girls had higher HDL-C in the youngest (<5 years, P = .05) and oldest age groups (15-19 years, P < .001). [[FH]] girls have higher levels of TC, LDL-C, and non-HDL-C levels than boys from birth up to 19 years of age. This may contribute significantly to the total lifelong cholesterol burden in [[FH]] women.
|mesh-terms=* Adolescent
* Aging
* Child
* Child, Preschool
* Cholesterol
* Female
* Humans
* Hyperlipoproteinemia Type II
* Infant
* Infant, Newborn
* Male
* Mutation
* Sex Characteristics
* Young Adult
|keywords=* Age
* Children
* Cholesterol
* Familial hypercholesterolemia
* Sex
|full-text-url=https://sci-hub.do/10.1016/j.jacl.2018.02.021
}}
{{medline-entry
|title=Association between lipoprotein (a) and proprotein convertase substilisin/kexin type 9 in patients with heterozygous familial hypercholesterolemia: A case-control study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29129821
|abstract=Recent data have suggested an important role of lipoprotein (a) [Lp(a)] and proprotein convertase substilisin/kexin type 9 ([[PCSK9]]) in the development of atherosclerotic cardiovascular disease (ASCVD) in both general population and family hypercholesterolemia ([[FH]]), while the relation of Lp(a) to [[PCSK9]] has not been examined. The aim of the present study was to investigate the association between plasma [[PCSK9]] and Lp(a)in patients with heterozygous [[FH]] (He[[FH]]). Two hundred and fifty-five molecularly confirmed patients with He[[FH]] were compared to 255 age- and gender-matched non-[[FH]] controls. Plasma [[PCSK9]] and Lp(a) concentrations were measured using ELISA and immunoturbidimetric method respectively, and finally their association was assessed. Both plasma [[PCSK9]] and Lp(a) levels were significantly higher in patients with He[[FH]] compared to control group (p<0.001). Besides, the Lp(a) concentration and percentage of Lp(a)≥300mg/L were increased by [[PCSK9]] tertiles in He[[FH]] group (both p<0.05) while not in control group. In partial correlation analysis, Lp(a) was associated with [[PCSK9]] (r=0.254, p<0.001) in He[[FH]] group but not in control, which were further confirmed by multivariable linear regression analysis. Furthermore, significant associations between Lp(a) and [[PCSK9]] were also found in subgroups of He[[FH]] group irrespective of definite or probable [[FH]], with and without coronary artery disease (CAD), and with statin or not. Plasma Lp(a) level was associated with [[PCSK9]] in patients with He[[FH]] alone, suggesting that much about the interaction of [[PCSK9]] with Lp(a) in [[FH]] need further explorations.
|mesh-terms=* Adult
* Aged
* Aging
* Case-Control Studies
* Coronary Artery Disease
* DNA
* Female
* Humans
* Hyperlipoproteinemia Type II
* Lipids
* Lipoprotein(a)
* Male
* Middle Aged
* Proprotein Convertase 9
* Risk Factors
|keywords=* Atherosclerosis
* Familial hypercholesterolemia
* Lipoprotein (a)
* Proprotein convertase subtilisin/kexin type 9
|full-text-url=https://sci-hub.do/10.1016/j.metabol.2017.11.004
}}
{{medline-entry
|title=Longitudinal Assessment of Self- and Informant-Subjective Cognitive Complaints in a Sample of Healthy Late-Middle Aged Adults Enriched with a Family History of Alzheimer's Disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28693655
|abstract=The purpose of this study was to investigate the longitudinal trajectory of self- and informant-subjective cognitive complaints (SCC), and to determine if SCC predict longitudinal changes in objective measures (OM) of cognitive function. The study included healthy and cognitively normal late middle-aged adults enriched with a family history of AD who were evaluated at up to three visits over a 4-year period. At each visit (Visit 1-3), self- and informant-SCC and OM were evaluated. Linear mixed models were used to determine if the longitudinal rate of change of self- and informant-SCC were associated with demographic variables, depressive symptoms, family history ([[FH]]), and apolipoprotein epsilon 4 (APOE4) status. The same modeling approach was used to examine the effect of Visit 1 SCC on longitudinal cognitive change after controlling for the same variables. At Visit 1, more self-SCC were associated with fewer years of education and more depressive symptoms. SCC were also associated with poorer performance on cognitive measures, such that more self-SCC at Visit 1 were associated with poorer performance on memory and executive functioning measures at Visit 1, while more informant-SCC were associated with faster rate of longitudinal decline on a measure of episodic learning and memory. [[FH]] and APOE4 status were not associated with SCC. Self- and informant-SCC showed an association with OM, albeit over different time frames in our late middle-aged sample. Additional longitudinal follow-up will likely assist in further clarifying these relationships as our sample ages and more pronounced cognitive changes eventually emerge. (JINS, 2017, 23, 617-626).
|mesh-terms=* Aging
* Alzheimer Disease
* Cognitive Dysfunction
* Diagnostic Self Evaluation
* Female
* Genetic Predisposition to Disease
* Humans
* Longitudinal Studies
* Male
* Middle Aged
|keywords=* Aging
* Dementia
* Executive function
* Memory
* Neuropsychology
* Self-report
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754023
}}
{{medline-entry
|title=Diffusion Tensor Imaging Predictors of Episodic Memory Decline in Healthy Elders at Genetic Risk for Alzheimer's Disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27903333
|abstract=White matter (WM) integrity within the mesial temporal lobe (MTL) is important for episodic memory (EM) functioning. The current study investigated the ability of diffusion tensor imaging (DTI) in MTL WM tracts to predict 3-year changes in EM performance in healthy elders at disproportionately higher genetic risk for Alzheimer's disease (AD). Fifty-one cognitively intact elders (52% with family history ([[FH]]) of dementia and 33% possessing an Apolipoprotein E ε4 allelle) were administered the Rey Auditory Verbal Learning Test (RAVLT) at study entry and at 3-year follow-up. DTI scanning, conducted at study entry, examined fractional anisotropy and mean, radial and axial diffusion within three MTL WM tracts: uncinate fasciculus (UNC), cingulate-hippocampal (CHG), and fornix-stria terminalis (FxS). Correlations were performed between residualized change scores computed from RAVLT trials 1-5, immediate recall, and delayed recall scores and baseline DTI measures; MTL gray matter (GM) and WM volumes; demographics; and AD genetic and metabolic risk factors. Higher MTL mean and axial diffusivity at baseline significantly predicted 3-year changes in EM, whereas baseline MTL GM and WM volumes, [[FH]], and metabolic risk factors did not. Both ε4 status and DTI correlated with change in immediate recall. Longitudinal EM changes in cognitively intact, healthy elders can be predicted by disruption of the MTL WM microstructure. These results are derived from a sample with a disproportionately higher genetic risk for AD, suggesting that the observed WM disruption in MTL pathways may be related to early neuropathological changes associated with the preclinical stage of AD. (JINS, 2016, 22, 1005-1015).
|mesh-terms=* Aftercare
* Aged
* Aged, 80 and over
* Aging
* Alzheimer Disease
* Apolipoprotein E4
* Diffusion Tensor Imaging
* Female
* Humans
* Male
* Memory, Episodic
* Prognosis
* Risk
* Temporal Lobe
* White Matter
|keywords=* Alzheimer’s disease
* Anatomical MRI
* Apolipoprotein E
* Diffusion tensor imaging
* Episodic memory
* Mesial temporal lobe
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916766
}}
{{medline-entry
|title=Familial hypercholesterolaemia reduces the quality of life of patients not reaching treatment targets.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27127013
|abstract=Familial hypercholesterolaemia ([[FH]]) is the most common monogenic disorder associated with premature cardiovascular disease. If untreated, life expectancy in heterozygous [[FH]] patients is shortened by 20-30 years compared with the general population. Nevertheless, treatment goals are only met in approximately 50% of patients. This comparative study examined the quality of life (QoL) impact of [[FH]] in patients who had and had not reached the target of treatment. Two qualitative focus group interviews were carried out with a total of ten [[FH]] patients. A semi-structured interview guide included questions identified in a preceding literature study. The data were analysed using a medical anthropological approach. While having [[FH]] did not have much impact on well-treated patients' QoL, patients who had not reached the treatment target had markedly more concerns. They had experienced severe side-effects and worried about their own and their relatives' health. They were concerned about the long-term impact of not being effectively treated including the risk that coronary heart disease could cause their premature death or disability and inability to care for their children, in particular. The women had issues with stigma and self-efficacy. The QoL impact of [[FH]] is related to treatment efficacy. These findings need to be addressed in the management of [[FH]] patients. Particular attention should be paid to those who are not presently reaching the target of treatment. The study was funded by a research grant from Amgen. not relevant.
|mesh-terms=* Adolescent
* Adult
* Aged
* Cardiovascular Diseases
* Child
* Early Diagnosis
* Female
* Focus Groups
* Humans
* Hyperlipoproteinemia Type II
* Life Expectancy
* Male
* Medication Adherence
* Middle Aged
* Patient Acceptance of Health Care
* Qualitative Research
* Quality of Life
* Risk Factors
* Young Adult

}}
{{medline-entry
|title=Effect of fetal hypothyroidism on tolerance to ischemia-reperfusion injury in aged male rats: Role of nitric oxide.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27074518
|abstract=Aging is associated with increased prevalence of cardiovascular disease. Thyroid hormone deficiency during fetal life decreases myocardial tolerance to ischemia-reperfusion (IR) injury in later life. The long-term effects of fetal hypothyroidism ([[FH]]) on response to IR injury in aged rats have not been well documented. The aim of this study was therefore to compare the effect of [[FH]] on tolerance to IR injury in young and aged male rats and to determine contribution of iNOS (inducible nitric oxide synthase), Bax, and Bcl-2. Pregnant female rats were divided into two groups: The [[FH]] group received water containing 0.025% 6-propyl-2-thiouracil during gestation and the controls consumed tap water. Isolated perfused hearts from young (3 months) and aged (12 months) rats were subjected to IR. Hemodynamic parameters, infarct size, and heart NOx (nitrite nitrate) levels were measured; in addition, mRNA expression of iNOS, Bax, and Bcl-2 and their protein levels in heart were measured. Recovery of post-ischemic LVDP and ±dp/dt were lower and infarct sizes were higher than controls in aged [[FH]] rats (68.38 ± 6.7% vs. 50.5 ± 1.7%; P < 0.05). Aged [[FH]] rats had higher heart NOx values than controls (74.3 ± 2.6 vs. 47.6 ± 2.5 μmol/L, P < 0.05). After IR, in [[FH]] rats, mRNA expression of iNOS and Bax were higher and Bcl-2 was lower in both the young (350 and 240% for iNOS and Bax, respectively and 51% for Bcl-2) and aged rats (504 and 567% for iNOS and Bax, respectively and 67% for Bcl-2). Compared to controls, in [[FH]] rats protein levels of iNOS (37% for young and 45% for aged rats) and Bax (94% for young and 118% for aged rats) were higher while for Bcl-2 (36% for young and 62% for aged rats) were lower. After IR, in [[FH]] rats, aminoguanidine, a selective iNOS inhibitor, decreased mRNA expression of iNOS and Bax and increased expression of Bcl-2 in both young (65% and 58% for iNOS and Bax, respectively and 152% for Bcl-2) and aged rats (76% and 64% for iNOS and Bax, respectively and 222% for Bcl-2). In addition, in the heart of [[FH]] rats, aminoguanidine decreased protein levels of iNOS (47% for young and 60% for aged rats) and Bax (57% for young and 80% for aged rats) and increased protein levels of Bcl-2 (124% for young and 180% for aged rats). In conclusion, thyroid hormone deficiency during fetal life decreases tolerance to IR injury in aged rats; this effect is at least in part, due to increased expression of iNOS and Bax-to-Bcl-2 ratio in the heart and is restored by iNOS inhibition.
|mesh-terms=* Aging
* Animals
* Congenital Hypothyroidism
* Creatine Kinase
* L-Lactate Dehydrogenase
* Male
* Myocardial Reperfusion Injury
* Myocardium
* Nitrates
* Nitric Oxide
* Nitric Oxide Synthase Type II
* Nitrites
* Proto-Oncogene Proteins c-bcl-2
* RNA
* Rats, Wistar
* Up-Regulation
* bcl-2-Associated X Protein
|keywords=* Aging
* Fetal hypothyroidism
* Ischemia-reperfusion injury
* Nitric oxide
* Rat
|full-text-url=https://sci-hub.do/10.1016/j.niox.2016.04.001
}}
{{medline-entry
|title=Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26009596
|abstract=Familial hypercholesterolaemia ([[FH]]) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with [[FH]] every minute. If diagnosed and treated early in childhood, individuals with [[FH]] can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of [[FH]] children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between [[FH]] and non-[[FH]] using LDL-C screening. An LDL-C ≥5 mmol/L (190 mg/dL), or an LDL-C ≥4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is ≥3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous [[FH]] is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous [[FH]]. Target LDL-C is <3.5 mmol/L (130 mg/dL) if >10 years, or ideally 50% reduction from baseline if 8-10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying [[FH]] early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and adolescents with [[FH]].
|mesh-terms=* Adolescent
* Adult
* Atherosclerosis
* Carotid Intima-Media Thickness
* Child
* Clinical Laboratory Techniques
* Cost of Illness
* Counseling
* Diet
* Dietary Supplements
* Early Diagnosis
* Economics, Medical
* Evidence-Based Medicine
* Female
* Genetic Testing
* Heterozygote
* Homozygote
* Humans
* Hyperlipoproteinemia Type II
* Life Expectancy
* Medication Adherence
* Middle Aged
* Pregnancy
* Pregnancy Complications
* Risk Factors
* Young Adult
|keywords=* Adolescents
* Children
* Consensus statement
* Diagnosis
* Ezetimibe
* Familial hypercholesterolaemia
* LDL cholesterol
* PCSK9 inhibitor
* Statin
* Treatment
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576143
}}
{{medline-entry
|title=Impact of family history of alcoholism on glutamine/glutamate ratio in anterior cingulate cortex in substance-naïve adolescents.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26025607
|abstract=Neuroimaging studies of individuals with family histories of alcoholism provide evidence suggesting neurobiological risk factors for alcoholism. Youth family history positive ([[FH]] ) for alcoholism exhibit increased impulsivity compared to family history negative ([[FH]]-) peers in conjunction with altered functional activation in prefrontal cortex, including anterior cingulate cortex (ACC). This study examined glutamate (Glu) and glutamine (Gln), amino acids vital to protein synthesis, cellular metabolism and neurotransmission, acquired from ACC and parieto-occipital cortex (POC) using magnetic resonance spectroscopy (MRS) at 4T. Participants were 28 adolescents (13 male, 12-14 yrs) and 31 emerging adults (16 male, 18-25 yrs), stratified into [[FH]]- and [[FH]] groups. Significantly higher ACC Gln/Glu was observed in emerging adults versus adolescents in [[FH]]- but not [[FH]] groups. In [[FH]]- adolescents, higher impulsivity was significantly associated with higher ACC Gln/Glu. In [[FH]] emerging adults, higher impulsivity was negatively associated with ACC Gln/Glu. No differences or associations were observed for POC. These findings provide preliminary evidence that family history of alcoholism is associated with a neurochemical profile that may influence normative age differences in glutamatergic metabolites and their association with impulse control, which together could confer greater genetic risk of addiction later in life.
|mesh-terms=* Adolescent
* Aging
* Alcoholism
* Brain Chemistry
* Child
* Female
* Glutamic Acid
* Glutamine
* Gyrus Cinguli
* Humans
* Impulsive Behavior
* Magnetic Resonance Imaging
* Magnetic Resonance Spectroscopy
* Male
* Young Adult
|keywords=* Adolescence
* Alcoholism
* Family history
* Glutamate
* Impulsivity
* MRS
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618784
}}
{{medline-entry
|title=Age-Based Differences in the Genetic Determinants of Glycemic Control: A Case of [[FOXO3]] Variations.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25993007
|abstract=Glucose homeostasis is a trait of healthy ageing and is crucial to the elderly, but less consideration has been given to the age composition in most studies involving genetics and hyperglycemia. Seven variants in [[FOXO3]] were genotyped in three cohorts (n = 2037; LLI, MI_S and MI_N; mean age: 92.5 ± 3.6, 45.9 ± 8.2 and 46.8 ± 10.3, respectively) to compare the contribution of [[FOXO3]] to fasting hyperglycemia ([[FH]]) between long-lived individuals (LLI, aged over 90 years) and middle-aged subjects (aged from 35-65 years). A different genetic predisposition of [[FOXO3]] alleles to [[FH]] was observed between LLI and both of two middle-aged cohorts. In the LLI cohort, the longevity beneficial alleles of three variants with the haplotype "AGGC" in block 1 were significantly protective to [[FH]], fasting glucose, hemoglobin A1C and HOMA-IR. Notably, combining multifactor dimensionality reduction and logistic regression, we identified a significant 3-factor interaction model (rs2802288, rs2802292 and moderate physical activity) associated with lower [[FH]] risk. However, not all of the findings were replicated in the two middle-aged cohorts. Our data provides a novel insight into the inconsistent genetic determinants between middle-aged and LLI subjects. [[FOXO3]] might act as a shared genetic predisposition to hyperglycemia and lifespan.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Blood Glucose
* Cross-Sectional Studies
* Fasting
* Female
* Forkhead Box Protein O3
* Forkhead Transcription Factors
* Gene Expression
* Genetic Predisposition to Disease
* Glycated Hemoglobin A
* Humans
* Hyperglycemia
* Insulin
* Insulin Resistance
* Logistic Models
* Longevity
* Male
* Middle Aged
* Multifactor Dimensionality Reduction

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439071
}}
{{medline-entry
|title=FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer's Disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25530915
|abstract=Having a parent affected by late-onset Alzheimer's disease (AD) is a major risk factor for cognitively normal (NL) individuals. This study explores the potential of PET with F-FDG and the amyloid- [i]β[/i] (A[i]β[/i]) tracer C-Pittsburgh Compound B (PiB) for detection of individual risk in NL adults with AD-parents. FDG- and PiB-PET was performed in 119 young to late-middle aged NL individuals including 80 NL with positive family history of AD ([[FH]] ) and 39 NL with negative family history of any dementia ([[FH]]-). The [[FH]] group included 50 subjects with maternal ([[FH]]m) and 30 with paternal family history ([[FH]]p). Individual FDG and PiB scans were Z scored on a voxel-wise basis relative to modality-specific reference databases using automated procedures and rated as positive or negative ( /-) for AD-typical abnormalities using predefined criteria. To determine the effect of age, the cohort was separated into younger (49 ± 9 y) and older (68 ± 5 y) groups relative to the median age (60 y). Among individuals of age >60 y, as compared to controls, NL [[FH]] showed a higher frequency of FDG scans vs. [[FH]]- (53% vs. 6% p < 0.003), and a trend for PiB scans (27% vs. 11%; p = 0.19). This effect was observed for both [[FH]]m and [[FH]]p groups. Among individuals of age ≤60 y, NL [[FH]]m showed a higher frequency of FDG scans (29%) compared to [[FH]]- (5%, p = 0.04) and a trend compared to [[FH]]p (11%) (p = 0.07), while the distribution of PiB scans was not different between groups. In both age cohorts, FDG scans were more frequent than PiB scans among NL [[FH]] , especially [[FH]]m (p < 0.03). FDG-PET was a significant predictor of [[FH]] status. Classification according to PiB status was significantly less successful. Automated analysis of FDG- and PiB-PET demonstrates higher rates of abnormalities in at-risk [[FH]] vs [[FH]]- subjects, indicating potentially ongoing early AD-pathology in this population. The frequency of metabolic abnormalities was higher than that of A[i]β[/i] pathology in the younger cohort, suggesting that neuronal dysfunction may precede major aggregated A[i]β[/i] burden in young NL [[FH]] . Longitudinal follow-up is required to determine if the observed abnormalities predict future AD.

|keywords=* Alzheimer’s Disease
* Amyloid Imaging
* Early Detection
* Glucose Metabolism
* Normal Aging
* Positron Emission Tomography
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270202
}}
{{medline-entry
|title=Randomized trial of the ForeseeHome monitoring device for early detection of neovascular age-related macular degeneration. The HOme Monitoring of the Eye (HOME) study design - HOME Study report number 1.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24530651
|abstract=To evaluate the effects of a home-monitoring device with tele-monitoring compared with standard care in detection of progression to choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), the leading cause of blindness in the US. Participants, aged 55 to 90 years, at high risk of developing CNV associated with AMD were recruited to the HOme Monitoring of Eye (HOME) Study, an unmasked, multi-center, randomized trial of the ForeseeHome ([[FH]]) device plus standard care vs. standard care alone. The [[FH]] device utilizes preferential hyperacuity perimetry and tele-monitoring to detect changes in vision function associated with development of CNV, potentially prior to symptom and visual acuity loss. After establishing baseline measurements, subsequent changes on follow-up are detected by the device, causing the monitoring center to alert the clinical center to recall participants for an exam. Standard care consists of instructions for self-monitoring visual changes with subsequent self-report to the clinical center. The primary objective of this study is to determine whether home monitoring plus standard care in comparison with standard care alone, results in earlier detection of incident CNV with better present visual acuity. The primary outcome is the decline in visual acuity at CNV diagnosis from baseline. Detection of CNV prior to substantial vision loss is critical as vision outcome following anti-angiogenic therapy is dependent on the visual acuity at initiation of treatment. HOME Study is the first large scale study to test the use of home tele-monitoring system in the management of AMD patients.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Choroidal Neovascularization
* Female
* Humans
* Macular Degeneration
* Male
* Middle Aged
* Prospective Studies
* Research Design
* Risk Factors
* Telemedicine
* Visual Acuity
* Visual Field Tests
|keywords=* Age-related macular degeneration
* Best-corrected visual acuity
* Choroidal neovascularization
* Controlled clinical trial
* Home-monitoring
|full-text-url=https://sci-hub.do/10.1016/j.cct.2014.02.003
}}
{{medline-entry
|title=Mild clinical presentation and prolonged survival of a patient with fumarase deficiency due to the combination of a known and a novel mutation in [[FH]] gene.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23612258
|abstract=Mutations in the [[FH]] gene cause the deficiency of the enzyme fumarase (fumarate hydratase, EC 4.2.1.2) which result in autosomal recessive fumaric aciduria in early childhood with failure to thrive, seizures, developmental delay, mental retardation, hypotonia and sometimes with polycythemia, leukopenia, and neutropenia. Many children with fumarate hydratase deficiency do not survive infancy or childhood; those surviving beyond childhood have severe psychomotor retardation. Recently, [[FH]] gene was also identified as a "non-classical" tumor suppressor gene and heterozygous mutations were shown to cause multiple cutaneous and uterine leiomyomas as well as hereditary leiomyomatosis and renal cell cancer. A male patient who was referred to investigate the etiology of psychomotor retardation was later diagnosed to have fumaric aciduria due to the combination of a previously known (c.1431_1433dupAAA) and a novel (c.782G>T) mutation. The patient had an unusually mild clinical course without acidotic attacks. Interestingly his father who was heterozygous for the c.1431_1433dupAAA mutation in the [[FH]] gene had cutaneous leiomyoma.
|mesh-terms=* Amino Acid Sequence
* Child
* Child, Preschool
* Fumarate Hydratase
* Genetic Predisposition to Disease
* Heterozygote
* Humans
* Infant
* Leiomyoma
* Life Expectancy
* Male
* Metabolism, Inborn Errors
* Molecular Sequence Data
* Muscle Hypotonia
* Mutation
* Psychomotor Disorders
* Survival Analysis

|full-text-url=https://sci-hub.do/10.1016/j.gene.2013.03.026
}}
{{medline-entry
|title=Height velocity curves in female patients with idiopathic scoliosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22744490
|abstract=Following identification of peak height velocity (PHV) by a recent study as a possible prognostic factor for curve progression in patients with idiopathic scoliosis (IS), the aim of this study was to investigate PHV curves in Japanese female patients with IS. The study subjects were 20 skeletally immature IS patients who were followed until maturity. The mean age and the mean pubertal status at the initial visit were 9.8 years and 24 months before menarche, respectively, with a follow-up period of 5.2 years. Height measurements were recorded at each visit, and HV was calculated as the change in height (cm) divided by the time interval (yr.) between visits of 6 to 12 months. The PHV, age at PHV (APHV), height at PHV (HPHV), and final height ([[FH]]) were determined. Patient HV curves were plotted using their HV data, and growth periods (GPs) were calculated from the curves. PHVs and GPs of study patients were compared to standard data from unaffected girls. The median values and interquartile ranges in PHV, APHV, HPHV, and [[FH]] were 8.5 cm/yr. (7.9-9.7), 11.8 yr. (11.2-12.1), 153.2 cm (150.1-155.8), and 160.1 cm (157.4-162.4), respectively. The median GP was 27 months. The PHV and GP values in IS female patients were higher and shorter than those in unaffected girls. These findings indicate that the patterns of height velocity curves in IS patients are different from those in unaffected girls, suggesting that curve progression in IS patients is associated with the magnitude of PHV and duration of GP. Recently, we have developed an HV reader to easily and quickly identify the present HV in patients with scoliosis, applicable for the clinical setting or school screening. We conclude that risk assessments of curve progression in patients with IS should include HV along with measures of skeletal maturity such as the Risser sign and/or digital skeletal age using hand X-rays.
|mesh-terms=* Adolescent
* Aging
* Body Height
* Child
* Female
* Humans
* Models, Biological
* Reproducibility of Results
* Scoliosis
* Sensitivity and Specificity
* Statistics as Topic

}}
{{medline-entry
|title=The [[LDLR]] deficient mouse as a model for aortic calcification and quantification by micro-computed tomography.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22051553
|abstract=Patients with familial hypercholesterolemia ([[FH]]) due mutations in the low-density lipoprotein receptor ([[LDLR]]) suffer premature aortic calcification, an effect that is age- and gene dosage-dependent and cholesterol level independent later in life. To better understand this process, we examined a murine model. We compared chow fed Ldlr(-/-) mice to controls at 6, 12 and 18 months and on a Western diet (WD) at 6 months. Additionally, we compared controls to Ldlr(-/-) mice and transgenic mice Tg(Pcsk9) overexpressing [[PCSK9]], which promotes [[LDLR]] degradation. Aortas were perfused-fixed, embedded in paraffin, and sections were stained with alizarin red. Micro-computerized tomography (micro-CT) was used to quantify vascular calcification. Ldlr(-/-) mice develop calcification in the ascending, transverse aorta and neck vessels with a distribution similar to that of human. Calcification was most prominent in 18-month-old Ldlr(-/-) mice fed a chow diet and in 6-month-old Ldlr(-/-) mice fed a WD. Interestingly, Tg(Pcsk9) mice fed a WD develop aortic calcifications as well. Histology confirmed that the calcification were predominantly sub-intimal. Marked expression of [[LRP5]] and WNT was observed in the Ldlr(-/-) and Tg(Pcsk9) models, but not in age-matched controls. The two mouse models develop aortic calcification in an age- and diet-dependent manner. Abnormal regulation of the [[LRP5]]/Wnt pathway may play a role in the calcification process. Further analysis of these aortic calcification models using this micro-CT imaging technique may provide a better understanding of the link between [[FH]] and arterial calcification.
|mesh-terms=* Age Factors
* Aging
* Animals
* Aortic Diseases
* Aortography
* Biomarkers
* Cholesterol
* Diet, High-Fat
* Disease Models, Animal
* Disease Progression
* Low Density Lipoprotein Receptor-Related Protein-5
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Mice, Transgenic
* Paraffin Embedding
* Proprotein Convertase 9
* Proprotein Convertases
* Receptors, LDL
* Serine Endopeptidases
* Severity of Illness Index
* Staining and Labeling
* Vascular Calcification
* Wnt Proteins
* X-Ray Microtomography

|full-text-url=https://sci-hub.do/10.1016/j.atherosclerosis.2011.08.035
}}
{{medline-entry
|title=Maturation and long-term hypoxia-induced acclimatization responses in PKC-mediated signaling pathways in ovine cerebral arterial contractility.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20702800
|abstract=In the developing fetus, cerebral arteries (CA) show striking differences in signal transduction mechanisms compared with the adult, and these differences are magnified in response to high-altitude long-term hypoxia (LTH). In addition, in the mature organism, cerebrovascular acclimatization to LTH may be associated with several clinical problems, the mechanisms of which are unknown. Because PKC plays a key role in regulating CA contractility, in fetal and adult cerebral arteries, we tested the hypothesis that LTH differentially regulates the PKC-mediated Ca(2 ) sensitization pathways and contractility. In four groups of sheep [fetal normoxic (FN), fetal hypoxic ([[FH]]), adult normoxic (AN), and adult hypoxic (AH)], we examined, simultaneously, responses of CA tension and intracellular Ca(2 ) concentration and measured CA levels of PKC, ERK1/2, RhoA, 20-kDa myosin light chain, and the 17-kDa PKC-potentiated myosin phosphatase inhibitor CPI-17. The PKC activator phorbol 12,13-dibutyrate (PDBu) produced robust contractions in all four groups. However, PDBu-induced contractions were significantly greater in AH CA than in the other groups. In all CA groups except AH, in the presence of MEK inhibitor (U-0126), the PDBu-induced contractions were increased a further 20-30%. Furthermore, in adult CA, PDBu led to increased phosphorylation of ERK1, but not ERK2; in fetal CA, the reverse was the case. PDBu-stimulated ERK2 phosphorylation also was significantly greater in [[FH]] than FN CA. Also, although RhoA/Rho kinase played a significant role in PDBu-mediated contractions of FN CA, this was not the case in [[FH]] or either adult group. Also, whereas CPI-17 had a significant role in adult CA contractility, this was not the case for the fetus. Overall, in ovine CA, the present study demonstrates several important maturational and LTH acclimatization changes in PKC-induced contractile responses and downstream pathways. The latter may play a key role in the pathophysiologic disorders associated with acclimatization to high altitude.
|mesh-terms=* Acclimatization
* Age Factors
* Aging
* Animals
* Calcium Signaling
* Cerebral Arteries
* Disease Models, Animal
* Enzyme Activation
* Enzyme Activators
* Fetal Hypoxia
* Gestational Age
* Hypoxia
* MAP Kinase Kinase Kinases
* Mitogen-Activated Protein Kinase 1
* Mitogen-Activated Protein Kinase 3
* Myosin Light Chains
* Phosphoprotein Phosphatases
* Phosphorylation
* Protein Kinase C
* Protein Kinase Inhibitors
* Sheep
* Time Factors
* Vasoconstriction
* rho-Associated Kinases
* rhoA GTP-Binding Protein

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980463
}}
{{medline-entry
|title=Long-term statin therapy is associated with better episodic memory in aged familial hypercholesterolemia patients in comparison with population controls.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20571223
|abstract=The cognitive status of aged familial hypercholesterolemia ([[FH]]) patients treated with long-term statin therapy was compared with that of population controls. A comprehensive cohort of 43 elderly (age > or = 65 years) patients all with the same [[FH]] North Karelia mutation living in North Karelia (eastern Finland) was identified, 37 of whom (aged 65 to 84 years) agreed to participate. All but one of these [[FH]] patients had been using statins for approximately 15 years. Population-based controls (aged 65 to 84 years, n= 309) were the participants of the Health 2000 Survey living in eastern Finland. The cognitive assessment was conducted with tests for verbal fluency, Word List Learning (WLL) and Word List Delayed Recall (WLDR) subtests in the Consortium to Establish a Registry for Alzheimer's disease test battery. After adjustment for age, gender, education, diabetes mellitus, and coronary heart disease, [[FH]] patients were more likely to be in the top tertile of the WLDR (Odds ratio (OR) 3.40, 95% confidence interval (CI) 1.52-7.63) and WLL3 (OR 2.83, 95% CI 1.28-6.25) subtests. When the [[FH]] patients were subdivided according to the median length of their statin therapy, the ORs to be in the top tertile in the WLDR subtest were 1.65 (95% CI 0.52-5.25) for those with less and 5.40 (95% CI 1.74-17.72) in those individuals with more than median length of statin therapy. In conclusion, aged [[FH]] patients receiving long-term statin therapy exhibited better episodic memory than population controls, and this association became even more pronounced with longer statin therapy.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Cognition
* Family Health
* Female
* Finland
* Health Surveys
* Humans
* Hydroxymethylglutaryl-CoA Reductase Inhibitors
* Hypercholesterolemia
* Logistic Models
* Male
* Mental Recall
* Time Factors

|full-text-url=https://sci-hub.do/10.3233/JAD-2010-091381
}}
{{medline-entry
|title=Renal vascular dysfunction precedes the development of renal damage in the hypertensive Fawn-Hooded rat.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20007352
|abstract=It is unknown whether generalized vascular dysfunction precedes the development of kidney disease. Therefore, we studied myogenic constriction and endothelium-mediated dilatory responses in two inbred Fawn-Hooded ([[FH]]) rat strains, one of which spontaneously develops hypertension, proteinuria, and glomerulosclerosis ([[FH]]H), whereas the other ([[FH]]L) does not. Small renal, mesenteric resistance arteries and thoracic aorta isolated from [[FH]] rats before (7 wk old) and after the development of mild proteinuria (12 wks old) were mounted in perfused and isometric set-ups, respectively. Myogenic response, endothelium-dependent relaxation, and the contribution of endothelium-mediated dilatory compounds were studied using their respective inhibitors. Myogenic reactivity was assessed constructing pressure-diameter curves in the presence and absence of calcium. At the age of 7 wk, renal arteries isolated from kidneys of [[FH]]H rats developed significantly lower myogenic tone compared with [[FH]]L, most likely because of excessive cyclo-oxygenase 1-mediated production of constrictive prostaglandins. Consequently, young [[FH]]H demonstrated reduced maximal myogenic tone (22 /- 4.8 vs. 10.8 /- 2.0%, P = 0.03) and the peak myogenic index (-6.9 /- 4.8 vs. 0.6 /- 0.8%/mmHg, P = 0.07 for [[FH]]L vs. [[FH]]H, respectively). Active myogenic curves obtained in mesenteric arteries isolated from 7-wk-old rats did not differ between either strain, demonstrating a similar level of systemic myogenic tone in [[FH]]L and [[FH]]H rats. Therefore, before any renal end-organ damage is present, myogenic response seems selectively impaired in renal vasculature of [[FH]]H rats. Aortic reactivity did not differ between [[FH]]L and [[FH]]H at the time points studied. The present study shows that vascular dysfunction in both small renal and systemic arteries precedes renal end-organ damage in a spontaneous model of hypertension-associated renal damage. These early vascular changes might be potentially involved in the increased susceptibility of [[FH]]H rats to renal injury.
|mesh-terms=* Age Factors
* Aging
* Animals
* Aorta, Thoracic
* Biological Factors
* Blood Pressure
* Cyclooxygenase 1
* Disease Models, Animal
* Disease Progression
* Dose-Response Relationship, Drug
* Endothelium, Vascular
* Hypertension
* Kidney
* Kidney Diseases
* Male
* Membrane Proteins
* Nitric Oxide
* Prostaglandins
* Proteinuria
* Rats
* Rats, Inbred Strains
* Renal Artery
* Renal Circulation
* Vasoconstriction
* Vasoconstrictor Agents
* Vasodilation
* Vasodilator Agents

|full-text-url=https://sci-hub.do/10.1152/ajprenal.00289.2009
}}
{{medline-entry
|title=Predicting drinking onset with discrete-time survival analysis in offspring from the San Diego prospective study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19959300
|abstract=Previous research has shown that an early onset of drinking is associated with a range of problematic drinking outcomes in adulthood. However, earlier drinking is also linked to additional characteristics that themselves predict alcohol problems including male gender, a family history ([[FH]]) of alcoholism, age, race, parental alcoholism, depression symptoms, prior drug use, and conduct problems. This study tested the relationship between the age of first drink (AFD) and a range of risk factors that predict the onset of alcohol use. Participants were offspring from the San Diego Prospective Study (SDPS) who were at least 15 years old at the time of their most recent interview (n=147). Discrete-time survival analysis (DTSA) was used to relate multiple characteristics to the hazard function of alcohol onset across a relevant age range. The results demonstrated the predicted relationships to AFD for conduct problems, male gender, prior marijuana use, and a [[FH]] of alcoholism, even when these characteristics were estimated together. Furthermore, an interaction occurred such that offspring with both conduct problems and marijuana use were at substantially higher risk for alcohol use onset during this time period than would be predicted from the effect of these two risk factors alone. However, age at interview, ethnicity, parent education, and depressive symptoms did not predict the pattern of onset of drinking. Implications for future research and prevention efforts are discussed.
|mesh-terms=* Adolescent
* Adolescent Behavior
* Adult
* Age of Onset
* Aging
* Alcohol Drinking
* California
* Conduct Disorder
* Family
* Fathers
* Follow-Up Studies
* Humans
* Interview, Psychological
* Male
* Marijuana Abuse
* Parent-Child Relations
* Prospective Studies
* Risk Factors
* Risk-Taking
* Sex Factors
* Survival Analysis
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822001
}}
{{medline-entry
|title=Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19005175
|abstract=At cross-section, cognitively normal individuals (NL) with a maternal history of late-onset Alzheimer disease (AD) have reduced glucose metabolism (CMRglc) on FDG-PET in the same brain regions as patients with clinical AD as compared to those with a paternal and a negative family history ([[FH]]) of AD. This longitudinal FDG-PET study examines whether CMRglc reductions in NL subjects with a maternal history of AD are progressive. Seventy-five 50- to 82-year-old NL received 2-year follow-up clinical, neuropsychological, and FDG-PET examinations. These included 37 subjects with negative family history of AD ([[FH]]-), 9 with paternal ([[FH]]p), and 20 with maternal AD ([[FH]]m). Two subjects had parents with postmortem confirmed AD. Statistical parametric mapping was used to compare CMRglc across [[FH]] groups at baseline, follow-up, and longitudinally. At both time points, the [[FH]] groups were comparable for demographic and neuropsychological characteristics. At baseline and at follow-up, [[FH]]m subjects showed CMRglc reductions in the parieto-temporal, posterior cingulate, and medial temporal cortices as compared to [[FH]]- and [[FH]]p (p < 0.001). Longitudinally, [[FH]]m had significant CMRglc declines in these regions, which were significantly greater than those in [[FH]]- and [[FH]]p (p < 0.05). A maternal history of Alzheimer disease (AD) predisposes normal individuals to progressive CMRglc reductions in AD-vulnerable brain regions, which may be related to a higher risk for developing AD.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Alzheimer Disease
* Brain
* Female
* Genetic Predisposition to Disease
* Glucose
* Heterozygote
* Humans
* Male
* Middle Aged
* Mothers

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677512
}}
{{medline-entry
|title=Structural basis for complement factor H linked age-related macular degeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17893204
|abstract=Nearly 50 million people worldwide suffer from age-related macular degeneration (AMD), which causes severe loss of central vision. A single-nucleotide polymorphism in the gene for the complement regulator factor H ([[FH]]), which causes a Tyr-to-His substitution at position 402, is linked to approximately 50% of attributable risks for AMD. We present the crystal structure of the region of [[FH]] containing the polymorphic amino acid His402 in complex with an analogue of the glycosaminoglycans (GAGs) that localize the complement regulator on the cell surface. The structure demonstrates direct coordination of ligand by the disease-associated polymorphic residue, providing a molecular explanation of the genetic observation. This glycan-binding site occupies the center of an extended interaction groove on the regulator's surface, implying multivalent binding of sulfated GAGs. This finding is confirmed by structure-based site-directed mutagenesis, nuclear magnetic resonance-monitored binding experiments performed for both H402 and Y402 variants with this and another model GAG, and analysis of an extended GAG-[[FH]] complex.
|mesh-terms=* Aging
* Binding Sites
* Complement Factor H
* Crystallography, X-Ray
* Gene Products, gag
* Ligands
* Models, Molecular
* Mutation
* Polysaccharides
* Protein Structure, Quaternary
* Protein Structure, Tertiary
* Sucrose
* Surface Properties

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118454
}}
{{medline-entry
|title=Cholesterol-years score is associated with development of senile degenerative aortic stenosis in heterozygous familial hypercholesterolemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17192697
|abstract=We retrospectively evaluated the frequency and identified the factors associated with the development of aortic stenosis (AS) in 96 patients with heterozygous familial hypercholesterolemia ([[FH]]). The frequency of AS was 31% (4/13) and that of critical stenosis was 15% (2/13) in older patients over the age of 70 years. All 4 patients with AS were female aged more than 70 years who were diagnosed with [[FH]] when aged more than 60 years. There were no significant differences in conventional coronary risk factors; however, the age at cardiac catheterization, age at diagnosis of [[FH]] and the cholesterol-years score (CYS) with AS were significantly higher than those without AS (p=0.006, p=0.017, p=0.021, respectively). In multiple regression analysis, CYS was a significant independent predictor for the development of AS (p=0.037) in 13 older patients over the age of 70 years. These results suggest that physicians should be aware that AS needs attention in older patients with heterozygous [[FH]], especially women who have been diagnosed late in life and those who have been inadequately treated.
|mesh-terms=* Adult
* Aged
* Aging
* Aortic Valve Stenosis
* Cholesterol
* Female
* Heterozygote
* Humans
* Hyperlipoproteinemia Type II
* Male
* Middle Aged
* Regression Analysis
* Retrospective Studies
* Time Factors

|full-text-url=https://sci-hub.do/10.5551/jat.13.323
}}
{{medline-entry
|title=Are short boys with constitutional delay of growth and puberty candidates for rGH therapy according to FDA recommendations?
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16549932
|abstract=According to FDA-approved guidelines, boys whose height predictions fall to 160 cm or less are considered for treatment with recombinant growth hormone (rGH). The aim of this study was to analyze the value of different height prediction methods by accurately identifying those boys with constitutional delay of growth and puberty (CDGP) in whom final height ([[FH]]) prognosis was poor (<or=160 cm) and who might therefore be candidates for this treatment modality. In 69 boys with CDGP diagnosed at a mean age of 14.9 /-1.2 years, [[FH]] prediction was calculated by means of Bayley-Pinneau (BP), Roche-Wainer-Tissen (RWT), Tanner-Whitehouse II (TWII) and target height ([[TH]]) methods. At the age of 22.6 /- 3.5 years their height was remeasured and the accuracy of height prediction was analyzed. In 6 men (8.7%) measured [[FH]] was <or=160 cm. Depending on the prediction method, different individual patients within the 14- to 16-year age range would have been candidates for rGH treatment. The BP method would have recruited 8 subjects of whom only 3 had [[FH]] <or=160 cm (sensitivity 50%, specificity 92%). The RWT and TW II methods identified only one recruit, and this patient did achieve [[FH]] <or=160 cm (sensitivity 17%, specificity 100%). None of the 8 subjects with [[FH]] <or=160 cm would have qualified for GH treatment using the [[TH]] method. In three boys none of the four methods predicted their final height <or=160 cm. Although some boys with CDGP may be considered the candidates for rGH treatment according to FDA recommendations, none of the available methods of prediction are sufficiently sensitive to reliably recruit 14- to 16-year-old boys whose final height will fall at or below 160 cm.
|mesh-terms=* Adolescent
* Adult
* Aging
* Body Height
* Bone and Bones
* Data Interpretation, Statistical
* Growth Disorders
* Growth Hormone
* Guidelines as Topic
* Humans
* Male
* Predictive Value of Tests
* Prognosis
* Puberty, Delayed
* Retrospective Studies
* Sensitivity and Specificity
* United States
* United States Food and Drug Administration

|full-text-url=https://sci-hub.do/10.1159/000092120
}}
{{medline-entry
|title=Reduced sympathoneural responses to the cold pressor test in individuals with essential hypertension and in those genetically predisposed to hypertension. No support for the "pressor reactor" hypothesis of hypertension development.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15485746
|abstract=The aim of this study was to examine the influences of genetic predisposition to hypertension and of age on the sympathetic nervous system response to the cold pressor test (CPT). A total of 32 young subjects (aged 27 /- 2 years) were studied: 11 normotensive subjects without a family history of hypertension ([[FH]]), 14 normotensive subjects with a strong family history of hypertension ([[FH]] ), and eight hypertensive subjects. In addition, 21 older subjects (aged 53 /- 2 years) were studied: 13 hypertensive and eight normotensive subjects. Blood pressure (BP), heart rate ([[HR]]), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during a 2-min period of a CPT. Both young and older hypertensive subjects had higher resting MSNA than did the normotensive ones (47 /- 7 v 29 /- 4 bursts per 100 heartbeats (P < .05) and 66 /- 4 v 40 /- 7 bursts per 100 heartbeats (P < .01), respectively). The CPT resulted in [[HR]] increases of similar magnitude in all groups of patients. The [[FH]] group displayed slightly less increase in systolic BP than that of the [[FH]]- group (P < .05). The MSNA increased to a far greater degree in [[FH]]- (103%) than in [[FH]] (32%) and in young hypertensive patients (12%) (P < .05). Similarly, MSNA change with the CPT was greater in older normotensive subjects than in older hypertensive patients (61% v 12%, P < .05). Our results show that a CPT induces sympathetic responses that are subnormal in hypertensive patients and those with a family history of hypertension, highlighting the importance of genetic factors in determining the sympathetic nervous reactivity to CPT.
|mesh-terms=* Adult
* Aging
* Blood Pressure
* Case-Control Studies
* Cold Temperature
* Female
* Genetic Predisposition to Disease
* Heart Rate
* Humans
* Hypertension
* Male
* Middle Aged
* Muscle, Skeletal
* Sympathetic Nervous System

|full-text-url=https://sci-hub.do/10.1016/j.amjhyper.2004.05.008
}}
{{medline-entry
|title=The angle between the Frankfort horizontal and the sella-nasion line. Changes in porion and orbitale position during growth.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15160248
|abstract=The starting point of this study was the statement made in the literature that the angle between the two reference planes Frankfort horizontal ([[FH]]) and sella-nasion line (SN) changes relatively little during growth. The growth-induced relocation of the orbitale (Or; anterior reference point of the [[FH]]) in relation to SN is known from implant studies, whereas the relocation of the porion (Po; posterior reference point of the [[FH]]) has been the subject of only little research. The present study was aimed at analyzing the factors contributing to the almost constant angle between [[FH]] and SN. The study material consisted of two groups of macerated skulls and the relevant lateral cephalograms. The first group comprised 32 skulls of individuals aged 2.5 to 5 years, and the second group ten skulls of individuals aged 18 to 20 years. A diagram showing the growth-dependent changes was prepared with reference to the mean values for the two groups. The cephalograms were superimposed on the anterior cranial base line at sella point (S). A 3.1 degrees increase in the angle between [[FH]] and SN during growth was recorded in our investigations. The distance between Or and SN increased by 3.9 mm while Po remained vertically almost constant with respect to SN. In sagittal direction the distance between Or and S also increased, while Po was displaced to almost the same extent in the opposite direction. The increasing vertical distance between the anterior and posterior reference points of [[FH]] and SN was largely compensated by the sagittal developments of the reference points Po and Or, so that the angle between these two planes changed very little. The relatively stable angle between [[FH]] and SN thus showed by no means a constant relationship of the four reference points to one another.
|mesh-terms=* Adolescent
* Adult
* Aging
* Cadaver
* Cephalometry
* Child, Preschool
* Face
* Female
* Humans
* Image Interpretation, Computer-Assisted
* Male
* Maxillofacial Development
* Nasal Bone
* Orbit
* Reference Values
* Reproducibility of Results
* Sella Turcica
* Sensitivity and Specificity
* Skull

|full-text-url=https://sci-hub.do/10.1007/s00056-004-0329-8
}}
{{medline-entry
|title=CYP21 genotype, adult height, and pubertal development in 55 patients treated for 21-hydroxylase deficiency.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/14671153
|abstract=In a retrospective study we evaluated long-term growth, pubertal developmental patterns to final height ([[FH]]), and medication in 55 patients (35 females) affected by 21-hydroxylase deficiency. The patients were classified into 3 groups according to predicted mutation severity: group A (11 women and 9 men), homozygous or compound heterozygous for null or In2 splice mutations [residual enzymatic activity (RA), <1%]; group B (11 women and 4 men), homozygous for I172N or R341P or R426H mutations (RA, approximately 2-3%) or compound heterozygous with any of the group A or B mutations; and group C (13 women and 7 men), homozygous for P30L or V281L or P453S mutations (RA, >30%) or compound heterozygous with any of the group A, B, or C mutations. Three patients showed unclassifiable genotypes. [[FH]] was similar in the female groups, whereas male patients in group B were shorter than males in groups A and C. Fifty-five percent of patients in group A, 33% in group B, and 40% in group C reached an [[FH]] within 0.5 SD of target height. Four of the 7 patients diagnosed via neonatal screening achieved an [[FH]] equal to or above the target height. In the entire group, early diagnosis (<1 yr) improved height outcome. Early diagnosed CAH patients who received lower cortisol equivalent doses during the first year of life reached a better [[FH]]. Our results underline the importance of mineralocorticoid therapy, as CAH subjects in groups A and B who did not receive this treatment showed reduced [[FH]]. Early diagnosis, the use of more physiological cortisol equivalent dosages during the first year of life, and the extension of mineralocorticoid therapy to all classical patients are shown to improve the auxological outcome. Genotypic analysis helped to interpret the height results of our cases and prospectively may represent a useful tool for improving the therapeutic choice and the height outcome.
|mesh-terms=* Adrenal Hyperplasia, Congenital
* Aging
* Body Height
* Child
* Child, Preschool
* Female
* Fertility
* Genotype
* Humans
* Infant
* Infant, Newborn
* Male
* Mineralocorticoids
* Prognosis
* Puberty
* Retrospective Studies
* Steroid 21-Hydroxylase

|full-text-url=https://sci-hub.do/10.1210/jc.2003-030123
}}
{{medline-entry
|title=Late or delayed induced or spontaneous puberty in girls with Turner syndrome treated with growth hormone does not affect final height.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12970282
|abstract=Although it has been well established that GH treatment increases final height ([[FH]]) in girls with Turner syndrome (TS), the optimal ages to start GH therapy and introduce estrogens for pubertal induction have not been defined. We evaluated retrospectively the influence of the age at onset of GH treatment and age at onset of puberty on [[FH]] of 186 adult TS women treated during childhood with GH. Puberty started spontaneously in 38 patients, and it was induced in 148 girls with ethinyl estradiol (mean /- SD starting dose, 66 /- 32 ng/kg.d). Patients with spontaneous or induced puberty were divided into quartiles on the basis of age at initiation of GH treatment (3-10, 10-12, 12-14, and 14-19 yr). [[FH]] was 151.7 /- 6.0 cm; there were no [[FH]] differences between patients with induced or spontaneous puberty, nor were there differences between the age quartiles. Puberty started earlier in the girls with spontaneous puberty than in those with induced puberty (12.4 /- 1.3 yr vs. 14.5 /- 1.9 yr; P < 0.0001). The age at onset of puberty was not related to [[FH]]. Pubertal growth was 15.4 /- 4.6 cm in the girls with spontaneous puberty and 8.6 /- 4.3 cm in the girls with induced puberty (P < 0.0001). We conclude that GH treatment results in a significant increase in [[FH]] in most TS girls. Under the conditions of GH treatment and induction of puberty that we have used, the age at start of GH treatment was not related to [[FH]]; in addition, late or delayed induced or spontaneous puberty did not affect [[FH]].
|mesh-terms=* Adolescent
* Aging
* Birth Weight
* Body Height
* Ethinyl Estradiol
* Growth
* Growth Hormone
* Humans
* Male
* Puberty
* Puberty, Delayed
* Regression Analysis
* Retrospective Studies
* Turner Syndrome

|full-text-url=https://sci-hub.do/10.1210/jc.2002-022040
}}
{{medline-entry
|title=Perinatal development of the rat hip joint with restrained fetal movement.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12196711
|abstract=We compared the structures of the femoral head ([[FH]]) of neonates between normal and operated legs with restrained fetal movement using an exo utero technique. At embryonic day (E) 16.5, one hind limb was sutured onto the embryonic membrane and the fetuses were allowed to develop exo utero until the term (E22.5). There was no significant difference in the largest diameter of the [[FH]] between the non-operated and operated side [[FH]] in the operated neonates and the [[FH]] of the non-operated neonates. By scanning electron microscopy, roughness and collagen fiber bundles, which were detected on the surface of the operated side [[FH]] at E18.5, disappeared at E22.5. However, the operated side [[FH]] was deformed and the surface cell arrangement was more irregular than that of the controls at E22.5 by light microscopy. These results suggest that the abnormality of cell arrangement caused by the restraint of fetal movement may induce the deformity and irregularity of the [[FH]] surface, although this operation may not disturb the basic cellular activities such as cell proliferation as well as the secretion of cartilage ma-trix and collagen fibers. To further investigate the recovery process in the operated newborns after releasing the restraint, we bred them artificially for a considerable period after birth. The operated side [[FH]] surface of the neonate bred for 45 hours was smoother than that at E22.5 and similar to that of the non-operated side [[FH]]. This result suggests that the proper movement of the extremities after birth may recover the deformity caused by restrained fetal joint movement.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Disease Models, Animal
* Embryo, Mammalian
* Female
* Femur
* Fetus
* Gestational Age
* Hip Dislocation, Congenital
* Hip Joint
* Microscopy, Electron, Scanning
* Pregnancy
* Rats
* Rats, Wistar
* Restraint, Physical

|full-text-url=https://sci-hub.do/10.1111/j.1741-4520.2002.tb00863.x
}}
{{medline-entry
|title=Statins in children. Why and when.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12063772
|abstract=There is now ample evidence to demonstrate that atherosclerosis begins in childhood and is significantly accelerated in certain genetic disorders, most notably familial hypercholesterolemia ([[FH]]). Untreated [[FH]], both the homozygous and heterozygous forms, carry a substantial burden of morbidity and mortality if left untreated or inadequately treated. Males with [[FH]] are at earlier and greater risk than females and thus should begin therapy earlier, preferably at about 10. While bile acid sequestrants have long been considered the drug of choice in children, they have never been approved for pediatric use by FDA, are poorly tolerated, marginally effective at lowering low-density lipoprotein cholesterol and have minimal well controlled studies in children upon which to adequately assess safety. Over the last decade statins have been studied extensively in children and adolescents, although many of these studies have also been poorly controlled, of short duration, too small and lack detailed assessment. However there has been at least one large, randomized, placebo-controlled and comprehensive study with lovastatin in adolescent males that indicated efficacy similar to that anticipated in adults and no apparent safety concerns. While additional well-controlled studies are needed, especially those focusing on surrogates of atherosclerosis to determine clinical benefit, it is opportune for re-evaluation of current treatment guidelines.
|mesh-terms=* Age Factors
* Aging
* Anticholesteremic Agents
* Arteriosclerosis
* Child
* Female
* Humans
* Hyperlipoproteinemia Type II
* Lovastatin
* Male
* Safety
* Sex Factors
* Treatment Outcome

}}
{{medline-entry
|title=The postglenoid tubercle: prevalence and growth.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11936200
|abstract=To quantify the prevalence and growth of the postglenoid tubercle in a skull sample and in children. a) ninety skulls ranging in age from between 2 years and adulthood, b) sixtyfour corrected lateral tomograms of left and right temporomandibular joints of 32 boys and girls. Their age range was between 9 and 11 years. Impressions of the temporal fossae of the skull material were taken with a silicone type impression material, using a face-bow for leveling the base of the impression parallel to the [[FH]] plane. Each impression was divided into two halves along a paramedian plane from the tip of the postglenoid tubercle through the middle of the articular eminence and the surface was photocopied to a 200% scale. Height was measured with an electronic caliper. The presence or absence of a postglenoid tubercle was established on the corrected tomograms. Seventy-nine percent of the skulls had a postglenoid tubercle. It steadily enlarged and reached almost its final dimension by the age of 13 years. On corrected tomograms, 66% of the children showed a postglenoid tubercle. a) the postglenoid tubercle exists in a high percentage of human temporomandibular joints b) growth is almost completed by the age of 13, and c) there exists a right-left symmetry.
|mesh-terms=* Adolescent
* Adult
* Aging
* Child
* Child, Preschool
* Cranial Fossa, Posterior
* Humans
* Infant
* Skull
* Temporal Bone

|full-text-url=https://sci-hub.do/10.1016/S0940-9602(02)80017-6
}}
{{medline-entry
|title=The contribution of renal transplantation to final adult height: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11793079
|abstract=Final adult height following renal transplantation was assessed in 237 recipients enrolled in NAPRTCS before the ages of 11 (girls) and 12 (boys) years and followed for at least 6 months with a functioning graft at or after 18 years of age. The overall change in standardized height ([[SDS]]) from baseline to final adult height ([[FH]]) was 0.0; however, delta [[SDS]] was significantly better for the youngest recipients (6-8 years) than for the older age group. Retarded [[FH]] was associated with higher average prednisone dosage and better [[FH]] was associated with good graft function. Low baseline [[SDS]] was also predictive of retarded [[FH]]. Final adult height continues to be suboptimal in the cyclosporine A era.
|mesh-terms=* Aging
* Body Height
* Child
* Creatinine
* Dose-Response Relationship, Drug
* Female
* Glucocorticoids
* Humans
* Kidney
* Kidney Transplantation
* Male
* Prednisone
* Risk Factors

|full-text-url=https://sci-hub.do/10.1007/s004670100002
}}
{{medline-entry
|title=The use of Achilles tendon ultrasonography for the diagnosis of familial hypercholesterolemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11472754
|abstract=Differentiating [[FH]] from other causes of hypercholesterolemia has important clinical and therapeutic implications but is often not possible by standard clinical criteria. As accumulation of cholesterol in tendon is generally considered as pathognomonic of [[FH]], we evaluated the sensitivity and specificity of clinical and ultrasonographic tendon characteristics using the data of 127 genetically ascertained [[FH]] and 160 controls with various lipid profiles. Upon clinical examination, none of the controls and 29% of [[FH]] individuals (17% [[FH]] women and 38% [[FH]] men) presented with xanthomata in Achilles tendons, but no female and only 6% of male [[FH]] patients also showed xanthomata in the extensor tendon of the hand. Amongst all possible quantitative parameters (thickness, breadth, section and roundness) of Achilles tendon (AT) measured by ultrasonography, the thickness presented the best receiver operating curves. AT thickness above 5.8 mm was the most useful threshold for diagnosis of [[FH]], procuring sensitivity of 75% and specificity of 85%. Analysis of variation of AT thickness with age and sex indicated that this clinical criterion performed better in females older than 45 and in males under 45. In patients carrying the [[APOB]]-R3500Q mutation, AT-thickness appeared significantly less important compared with those carrying [[LDLR]] mutations. In conclusion, this study recommends identification of possible [[FH]] individuals amongst hypercholesterolemic patients using a criteria of AT-thickness over 5.8 mm eventually associated with a specific genetic test for [[APOB]]-R3500Q mutation.
|mesh-terms=* Achilles Tendon
* Adult
* Aging
* Apolipoproteins B
* Female
* Hand
* Humans
* Hyperlipoproteinemia Type II
* Male
* Middle Aged
* Muscular Diseases
* Mutation
* ROC Curve
* Receptors, LDL
* Sensitivity and Specificity
* Tendons
* Ultrasonography
* Xanthomatosis

|full-text-url=https://sci-hub.do/10.1016/s0021-9150(01)00533-0
}}
{{medline-entry
|title=Treatment of central precocious puberty: lessons from a 15 years prospective trial. German Decapeptyl Study Group.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10969917
|abstract=There is still controversy about the auxological outcome of GnRH agonist treatment in patients with CPP and about the favorable age and auxological characteristics at start of treatment for achieving a normal final height ([[FH]]) or for preserving height potential. We analyzed the [[FH]] data of 52 young women from a prospective multicentric trial which was started in 1985. The aim of this analysis was to determine factors that may predict a favorable [[FH]] or a good height gain. Chronological age (CA) was 5.2 /- 2.1 yr ( /- SD) at start of puberty, 6.2 /- 2.0 yr at start of triptorelin depot treatment, 11.1 /- 1.1 yr at end of treatment, and 16.7 /- 2.6 yr at [[FH]] evaluation. After 4.8 /- 2.2 yr (1.1-9.9 yr) of treatment duration, [[FH]] was 160.6 /- 8.0 cm (vs 154.9 /- 9.6 cm of initial height prediction [[[PAH]]], p<0.05). A [[FH]] within [[TH]] range or in excess of mean [[TH]] was achieved by 78% or 41% of patients. [[FH]] was above the 3rd percentile of the normal German population in 29% of patients (63% had an initial [[PAH]] < 156 cm). The group of patients with start of puberty at age < or = 6 yr (Group 1) showed a significantly higher height gain ([[FH]] - initial [[PAH]]) and lower height deficit compared to [[TH]] than older patients (Group 2). Furthermore, the percentage of patients from Group 1 reaching [[TH]] range or mean [[TH]] showed a significant increase with GnRH agonist treatment whereas this was not the case in Group 2. Stepwise regression analysis showed that height [[SDS]] at end of treatment, age at menarche, bone age (BA) at start of treatment, and BA advancement at end of treatment were determinants of [[FH]] (r2=0.923). Initial BA advancement and treatment duration were the factors that explained 68% of the variability of height gain. Although BA advancement at initiation of treatment was negatively associated with [[FH]] it was a positive predictor of height gain. In addition, height gain correlated significantly with CA and BA at start of treatment (r= -0.430, p=0.004 and r=0.359, p=0.018). Growth after interruption of treatment had no significant predictive effect on [[FH]]. It is concluded that a higher percentage of patients below 6 yr of age at start of puberty do profit from GnRH agonist treatment with respect to achieving a normal [[FH]]. BA, BA advancement, and height [[SDS]] at treatment start are important factors for determining outcome.
|mesh-terms=* Aging
* Body Height
* Brain Diseases
* Child
* Child, Preschool
* Delayed-Action Preparations
* Female
* Gonadotropin-Releasing Hormone
* Humans
* Infant
* Menarche
* Prospective Studies
* Puberty, Precocious
* Time Factors
* Treatment Outcome
* Triptorelin Pamoate

|full-text-url=https://sci-hub.do/10.1515/jpem.2000.13.s1.747
}}
{{medline-entry
|title=Corneal arcus, case finding and definition of individual clinical risk in heterozygous familial hypercholesterolaemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9894796
|abstract=Premature corneal arcus may identify individuals with hyperlipidaemia and increased cardiovascular risk. We have attempted to quantitate relationships through determination of graded prevalence of corneal arcus with age for 81 males and 73 females suffering from heterozygous familial hypercholesterolaemia (H[[FH]]) at presentation, and for 280 male and 353 female unselected patients (age range 16-76 years) attending a country general practice. Some degree of arcus affected 50% of H[[FH]] patients by age 31-35 years, and 50% of practice patients by age 41-45 years. Complete full ring arcus affected 50% of the familial hypercholesterolaemia ([[FH]]) group by age 50 years, with only 5% similarly affected in the non-[[FH]] group. Arcus grade with age was advanced by some 5 years in males versus females. Premature arcus potentially alerting to H[[FH]] can be broadly defined for males and females combined, as heavy full ring by age 50 years, or any degree of arcus by age 30-35 years. Arcus grade was not related to the presence of coronary disease. Accelerated development of corneal arcus with age is an indicator of H[[FH]], but premature arcus is not an additional marker of premature coronary disease for individual cases of H[[FH]].
|mesh-terms=* Adolescent
* Adult
* Aged
* Aging
* Arcus Senilis
* Coronary Disease
* Female
* Heterozygote
* Humans
* Hyperlipoproteinemia Type II
* Male
* Middle Aged
* Prevalence
* Risk Factors

|full-text-url=https://sci-hub.do/10.1111/j.1399-0004.1998.tb03770.x
}}
{{medline-entry
|title=Watanabe rabbits with heritable hypercholesterolaemia: a model of atherosclerosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9690137
|abstract=Many factors play important roles in the development of atherosclerotic lesions. The leading risk factor for atherosclerosis is familial hypercholesterolaemia ([[FH]]). [[FH]] is a genetic disease characterized by a deficiency of receptors for low density lipoprotein (LDL) on the plasmalemma of endothelial cells, a high level of serum LDL, and early development of atherosclerosis and skin xanthoma. Watanabe and colleagues have developed a line of rabbits with unprovoked hypercholesterolaemia, increased blood level of LDL, pronounced atherosclerosis and skin xanthoma. These Watanabe Heritable Hyperlipidaemic (WHHL) rabbits possess an inheritable mutation of one gene, similar to that in human [[FH]]. The morphogenesis of atherosclerosis in patients with [[FH]] is characterized by multifocal deposit of lipids in the stromal cells of thymus, spleen, skin, interstitial and parenchymatous cells of kidneys and the presence of some single foam cells in aorta. The manifestation of atherosclerotic lesions in WHHL rabbits increases progressively with age but the presence of atherosclerotic lesions in newborn WHHL rabbits suggest that the process may commence in utero. Moreover, the main mass of plasma cholesterol in WHHL rabbits is first found in LDL and to a lesser degree in lipoproteins of intermediate density. This is contrary to diet-induced atherosclerosis in rabbits where the main mass of serum cholesterol is found in very low density beta-lipoproteins. Thus the distribution of cholesterol among lipoprotein fractions differs from that in WHHL rabbits. Atherosclerotic damage of arteries in WHHL rabbits goes through several stages. During the progression of intimal damage, lipid and foam cell deposits are found in the internal surface together with developing plaques and increased content of lipids in the tunica media. Calcification often follows this process. The main factors initiating atherosclerosis in WHHL rabbits are adhesion of leukocytes and platelets to endothelial cells and the accumulation of lipids in the aortic wall. The deposits of lipids in macrophages and intimal smooth muscle cells in WHHL rabbits occurs mostly at the expense of cytoplasmic neutral lipid particles with some accumulation in lysosomes. Hypertension as a risk factor increases the area of atherosclerotic damage in all arterial vessels in WHHL rabbits, particularly in the thoracic and abdominal aorta. Morphogenesis of the development of atherosclerosis in WHHL and diet-induced atherosclerosis in rabbits was similar, but differs from rats with heritable hypercholesterolaemia. Damage or loss of endothelial cells can predispose the atherosclerotic vessels to vasospasm and can leave vessels unprotected against vasoconstrictor stimuli. The development of the WHHL model has not only given insight into the mechanisms of development of familial hypercholesterolaemia but has also provided a model for assessing various therapeutic approaches for the prevention and treatment of atherosclerosis.
|mesh-terms=* Aging
* Animals
* Arteriosclerosis
* Disease Models, Animal
* Hemodynamics
* Humans
* Hyperlipoproteinemia Type II
* Lipid Metabolism
* Rabbits
* Rats

|full-text-url=https://sci-hub.do/10.14670/HH-13.797
}}
{{medline-entry
|title=Final height in girls with slowly progressive untreated central precocious puberty.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9385528
|abstract=A group of six girls with slowly progressive idiopathic precocious puberty ([[IPP]]) and a good initial height prognosis was followed without treatment. At first observation the girls had a bone age advance over chronological age of no more than 18 months, a delta height age (delta HA): delta bone age (delta BA) ratio higher than 0.9 and height prognosis was unimpaired after 6 months. During the first two years of follow-up the girls maintained an acceptable height potential. The delta HA:delta BA ratio remained constant at greater than 0.9. Predicted height showed a slight increase or decrease ( /- 4 cm). The girls were reevaluated after the age of 14 years and followed-up until they reached their final height ([[FH]]). The mean [[FH]] (155.4 /- 2.8 cm) was below the mean target height (159.3 /- 4.2 cm) by 3.9 cm (range -2.1 to -6.7 cm); this difference was not statistically significant. The [[FH]] was more than 5 cm below the target height in only one case; this girl had the most precocious onset of puberty, at 6 years of age. In three cases [[FH]] was between the 3rd and 10th centiles. These three girls had a target height below 158 cm (< 25th centile). Girls with slowly progressive [[IPP]] and a good initial height prognosis preserved height potential with an acceptable final height without therapy.
|mesh-terms=* Age Determination by Skeleton
* Aging
* Body Height
* Child
* Female
* Follicle Stimulating Hormone
* Humans
* Luteinizing Hormone
* Ovary
* Prognosis
* Puberty, Precocious
* Ultrasonography
* Uterus

|full-text-url=https://sci-hub.do/10.3109/09513599709152552
}}
{{medline-entry
|title=Comparison of the effect of two low-density lipoprotein receptor class mutations on coronary heart disease among French-Canadian patients heterozygous for familial hypercholesterolaemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9179542
|abstract=The aim of this study was to compare the age at first elective coronary angiogram and the age at first revascularization (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) in 102 patients without familial hypercholesterolaemia ([[FH]]), who were matched for age and sex with 76 heterozygous [[FH]] patients carrying a defective allele at the low-density lipoprotein (LDL) receptor gene (LDL-R) and 26 heterozygous [[FH]] patients bearing a null mutation at the LDL-R. The prevalence of diabetes was significantly higher in the non-[[FH]] group than in the two [[FH]] groups (P < 0.05). Furthermore, mean body mass index (BMI) and waist circumference values were also higher in the non-[[FH]] group than in the two [[FH]] heterozygous groups (P < 0.005). However, [[FH]] patients who were null allele carriers had the highest plasma total and LDL-cholesterol levels and the highest cholesterol/HDL-cholesterol ratio, whereas the defective allele carriers group had intermediate levels between null allele carriers and non-[[FH]] patients. Comparison of the age at first coronary angiography revealed that the null allele carriers group were younger at first angiogram than the non-[[FH]] patients (P < 0.005). In addition, a trend was observed for a younger age at first angiogram in [[FH]] heterozygotes bearing a null allele than in carriers of a defective allele (P = 0.06). Moreover, null allele carriers were younger at first revascularization than defective allele carriers (P < 0.005) or non-[[FH]] patients (P < 0.005). Finally, the mean number of diseased vessels with > 50% stenosis was higher in null allele carriers than in non-[[FH]] patients and tended to be higher than among defective allele carriers (P < 0.01). Although no difference in plasma Lp(a) levels were noted between null allele carrier and non-[[FH]] patients, plasma Lp(a) concentrations were higher in the defective allele group than in the other two groups. In summary, the development of coronary artery disease as estimated by the age at first elective coronary angiography or at first revascularization is premature in [[FH]] patients carrying a null mutation compared with defective allele carriers or with non-[[FH]] patients. Moreover, the higher number of stenosed vessels among null allele carriers suggests that coronary artery disease was more severe in [[FH]] subjects with a null allele at the LDL-R locus.
|mesh-terms=* Adult
* Aging
* Angioplasty, Balloon, Coronary
* Body Constitution
* Body Mass Index
* Coronary Angiography
* Coronary Artery Bypass
* Coronary Disease
* Female
* Heterozygote
* Humans
* Hyperlipoproteinemia Type II
* Lipoprotein(a)
* Male
* Middle Aged
* Mutation
* Quebec
* Receptors, LDL

|full-text-url=https://sci-hub.do/10.1046/j.1365-2362.1997.1250669.x
}}
{{medline-entry
|title=Differences in the phenotype between children with familial defective apolipoprotein B-100 and familial hypercholesterolemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9157944
|abstract=Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited genetic disorder resulting from a point mutation in the apolipoprotein (apo) B gene and is associated with significantly elevated plasma total and LDL cholesterol levels. Despite numerous descriptions outlining the phenotype of children with familial hypercholesterolemia ([[FH]]), no study has described the biochemical and clinical phenotype in a cohort of children with FDB. The phenotypes of [[FH]] and FDB, therefore, have not been compared in children. We have studied a cohort of 38 Dutch children (all <20 years old) with FDB from 21 different families. Lipid and lipoprotein levels and the clinical phenotype were compared with 97 age-matched [[FH]] heterozygotes, as defined by molecular analysis, and with age-matched non-FDB, non-[[FH]] control subjects. Female FDB carriers (n=23) had significantly lower total cholesterol (P<.001), LDL cholesterol (P=.001), total cholesterol:HDL ratio (P<.001), and apoB levels (P=.001) than age-matched female [[FH]] heterozygotes (n=50). Similar results were noted in male FDB carriers (n=15) compared with male [[FH]] heterozygotes (n=47; P=.005, P=.007, P=.014, and P=.074, respectively). Within the FDB group, female FDB heterozygotes had higher LDL cholesterol (P=.038) and a trend to higher total cholesterol levels (P=.165) than age-matched males. Both male and female FDB carriers had significantly higher total cholesterol, LDL cholesterol, and total cholesterol:HDL ratio than age- and sex-matched control subjects, which was evident even in children <10 years of age, providing additional evidence that this mutation is penetrant in early life. These results provide evidence for a milder biochemical phenotype in children with FDB than in children with [[FH]]. The phenotype observed is intermediate between that of control subjects and [[FH]] heterozygotes matched for age and sex. As the incidence of coronary artery disease is related to both the extent and duration of cholesterol elevation, our findings might explain in part the lower incidence of clinical atherosclerosis seen in adults with this condition than in adults with [[FH]].
|mesh-terms=* Adolescent
* Adult
* Aging
* Apolipoprotein B-100
* Apolipoproteins B
* Child
* Child, Preschool
* Cholesterol
* Cholesterol, HDL
* Cholesterol, LDL
* Female
* Heterozygote
* Humans
* Hyperlipoproteinemia Type II
* Male
* Netherlands
* Phenotype
* Point Mutation
* Reference Values

|full-text-url=https://sci-hub.do/10.1161/01.atv.17.5.826
}}
{{medline-entry
|title=Final height outcome in both untreated and testosterone-treated boys with constitutional delay of growth and puberty.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/8961126
|abstract=The present retrospective study is based on a historical follow-up of 49 boys with constitutional delay of growth and puberty (CDGP) who went into puberty spontaneously (27 cases) or induced by depotestosterone treatment, 50 mg/ month for 6 months (22 cases). At the time of puberty the two groups of boys were similar in bone age, height deficiency, target height ([[TH]]) and had similar predicted final heights ([[FH]]). Their [[FH]] was measured and compared with [[TH]] calculated from measured parents' heights. [[FH]] did not significantly differ between the untreated boys and those treated. In the two groups of patients [[FH]] was similar and corresponded to both [[TH]] and height predicted at puberty onset. This study confirms that most boys with CDGP spontaneously attain a [[FH]] within the target range (24/27 cases). A short-term and low dose course of depotestosterone can be used without adverse effects on [[FH]]. The Bayley-Pinneau method can be generally considered accurate for predicting [[FH]] in CDGP, although significant discrepancies between [[FH]] and predicted height have been recorded in a fair number of both untreated and treated boys.
|mesh-terms=* Adolescent
* Age Determination by Skeleton
* Aging
* Body Height
* Bone Development
* Humans
* Male
* Puberty
* Puberty, Delayed
* Retrospective Studies
* Testosterone

|full-text-url=https://sci-hub.do/10.1515/jpem.1996.9.5.511
}}
{{medline-entry
|title=Effect of temperature and food intake on metabolic rate and posture of preruminant calves.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/8804665
|abstract=Influence of feeding level and temperature on posture and posture-related heat production was studied in preruminant calves. Twenty-four young calves were assigned in a 2 x 2 factorial design to one of two feeding levels [high ([[FH]]) or low (FL)] and to one of two temperature (7.5 degrees C or 19 degrees C). Heat production ([[HP]]) and posture were measured per calf every 9 min, during 3 days. [[HP]] was dependent on feeding level and temperature. Energy expenditure related to standing was higher at 7.5 degrees C than at 19 degrees C. Time spent standing was higher at FL than at [[FH]], and at 7.5 degrees C than at 19 degrees C. On the contrary, the number of standing periods was lower at 7.5 degrees C than at 19 degrees C. Consequently, the duration of a standing period was higher at 7.5 degrees C than at 19 degrees C. Within a standing period, [[HP]] decreased with time. This decline was largest at 7.5 degrees C. Thus, energy cost of standing was lower in treatments with a longer duration of a standing period. These results demonstrated that the effect of temperature on energy cost of standing is influenced by the number of standing periods.
|mesh-terms=* Acclimatization
* Aging
* Animals
* Body Temperature Regulation
* Cattle
* Energy Intake
* Energy Metabolism
* Male
* Motor Activity
* Posture
* Weaning

|full-text-url=https://sci-hub.do/10.1016/0031-9384(95)02221-x
}}
{{medline-entry
|title=Phenotypic variation among familial hypercholesterolemics heterozygous for either one of two Afrikaner founder LDL receptor mutations.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/8399083
|abstract=Two common founder-related gene mutations that affect the low-density lipoprotein receptor ([[LDLR]]) are responsible for approximately 80% of familial hypercholesterolemia ([[FH]]) in South African Afrikaners. The [[FH]] Afrikaner-1 ([[FH]]1) mutation (Asp206-->Glu) in exon 4 results in defective receptors with approximately 20% of normal activity, whereas the [[FH]] Afrikaner-2 ([[FH]]2) mutation (Val408-->Met) in exon 9 completely abolishes [[LDLR]] activity (< 2% normal activity). We analyzed the contribution of these mutations and other factors on the variation of hypercholesterolemia and clinical features in Afrikaner [[FH]] heterozygotes. The type of [[FH]] mutation, plasma triglyceride levels, and age of patients each contributed significantly to the variation in hypercholesterolemia, whereas smoking status, high-density lipoprotein cholesterol levels, and gender had no influence. Although all [[FH]] heterozygotes had frank hypercholesterolemia, patients with the [[FH]]1 mutation had significantly lower cholesterol levels than those with the [[FH]]2 mutation. [[FH]]1 heterozygotes also tended to have milder clinical features. The differences between the two [[FH]] groups could not be explained by a difference in the common apolipoprotein E variants. This study demonstrates that mutational heterogeneity in the [[LDLR]] gene influences the phenotypic expression of heterozygous [[FH]].
|mesh-terms=* Adult
* Aged
* Aging
* Apolipoproteins E
* European Continental Ancestry Group
* Female
* Heterozygote
* Humans
* Hyperlipoproteinemia Type II
* Lipids
* Lipoproteins
* Male
* Middle Aged
* Mutation
* Phenotype
* Polymorphism, Genetic
* Receptors, LDL
* Sex Characteristics
* South Africa

|full-text-url=https://sci-hub.do/10.1161/01.atv.13.10.1460
}}
{{medline-entry
|title=Plasma renin activity decrease precedes spontaneous focal glomerular sclerosis in aging rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/6750424
|abstract=An association between the activity of the renin-angiotensin system and the development of spontaneous focal glomerular sclerosis (FGS) in rats has been observed: the onset is preceded by a decrease in plasma renin activity (PRA). This observation was facilitated by the use of Fawn-hooded rats, which develop spontaneous FGS at an early age. Male Fawn-hooded rats develop severe FGS as early as 3 months of age. Male Wistar rats do not develop similar lesions until after 1 year of age. Correspondingly the PRA drops much sooner in Fawn-hooded than in Wistar rats. The low PRA appears to be due to low plasma renin rather than a limitation of the renin substrate, angiotensinogen, which appears to be present in the Fawn-hooded plasma in nonlimiting quantities. In the [[FH]] male rats renin content of the kidney drops only after severe glomerular pathology is evident, implying that the low PRA may be due to a decrease in renin secretion by the chromaffin cells of the juxtaglomerular apparatus.
|mesh-terms=* Aging
* Angiotensinogen
* Animals
* Female
* Glomerulonephritis
* Glomerulosclerosis, Focal Segmental
* Juxtaglomerular Apparatus
* Male
* Rats
* Rats, Inbred Strains
* Renin
* Renin-Angiotensin System

|full-text-url=https://sci-hub.do/10.1159/000182654
}}
{{medline-entry
|title=Contrasting effects of early and late orchiectomy on hypertension and renal disease in fawn-hooded rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/3650658
|abstract=Fawn-hooded ([[FH]]) rats, primarily males, develop spontaneous low-renin hypertension associated with reduced urinary excretion of kallikrein as early as 2 months of age, followed by progressive glomerular sclerosis and proteinuria as early as 3 months of age. In the present study we determined the effects of early (5-7 weeks) or late (5 months) orchiectomy on the blood pressure and nephropathy of [[FH]] rats, compared to sham-operated (control) [[FH]] males. Early orchiectomy reduced significantly the progression of glomerular sclerosis and of proteinuria and ameliorated the hypertension but had no significant effect on excretion of urinary kallikrein. Late orchiectomy, in contrast, had no significant effect on the progression of glomerular sclerosis or proteinuria but did significantly reduce the blood pressure and marginally increase the excretion of urine kallikrein. These results suggest that (a) male sex hormones may play a role in the pathogenesis of hypertension and nephropathy in the [[FH]] rats and (b) renal disease in this strain progresses in spite of improvement in blood pressure.
|mesh-terms=* Aging
* Androgens
* Animals
* Hypertension
* Kallikreins
* Kidney
* Kidney Diseases
* Male
* Orchiectomy
* Proteinuria
* Rats
* Rats, Inbred Strains
* Sex Characteristics

|full-text-url=https://sci-hub.do/10.1016/0024-3205(87)90731-4
}}
{{medline-entry
|title=Relationship between blood pressure level, renal histopathological lesions and plasma renin activity in fawn-hooded rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/3555593
|abstract=The fawn-hooded rat ([[FH]] rat) develops hypertension accompanied with focal and segmental glomerulosclerosis and proteinuria, resulting in premature death. In a first experiment the relationship between renal lesions and blood pressure at various ages was investigated. In a second experiment blood pressure was measured weekly from 10 to 38 weeks of age in a number of male [[FH]] rats, followed by examination of renal tissues at 40 weeks of age. Plasma renin activity (PRA) had also been determined in individual [[FH]] rats. [[FH]] rats aged 4.5 weeks had no renal morphological abnormalities. The severity of the glomerulosclerosis increased with age and showed a positive relationship with blood pressure. The scores of the proteinaceous tubular casts also increased with age and they, too, showed a positive correlation with blood pressure. The severity of glomerulosclerosis and proteinaceous casts at 40 weeks of age was related positively to the course of blood pressure throughout life. The final blood pressure level showed a positive correlation with final PRA values. Only [[FH]] rats with malignant nephrosclerosis had high PRA values. The renal glomerular and vascular lesions in the [[FH]] rat, most likely caused by the hypertension, progressively deteriorate to malignant nephrosclerosis. At that stage PRA values are increased and may be contributing to the development of renal vascular lesions and acceleration of the hypertension.
|mesh-terms=* Aging
* Animals
* Blood Pressure
* Glomerulonephritis
* Hypertension, Renal
* Kidney
* Male
* Proteinuria
* Rats
* Rats, Inbred SHR
* Renal Artery
* Renin

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2013019
}}
{{medline-entry
|title=Fecal alpha 1-antitrypsin and hemoglobin excretion in healthy human milk-, formula-, or cow's milk-fed infants.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/3090512
|abstract=There is concern that whole cow's milk feedings may be associated with intestinal abnormalities in infants. We studied this issue by measuring random fecal samples for alpha 1-antitrypsin (FA1AT) and hemoglobin ([[FH]]) concentrations in 820 healthy infants up to 12 months of age. Subjects were fed either human milk, formula, or fresh whole cow's milk. Solid foods were given ad libitum. Fecal samples were also tested for occult blood with Hematest reagent tablets. None of the infants younger than 6 months of age were receiving fresh whole cow's milk. We found small but statistically significant differences in mean FA1AT between the three feeding groups (P less than .0001): human milk (n = 354) greater than formula (n = 320) greater than cow's milk (n = 146). The younger subjects fed either formula or human milk tended to have higher FA1AT concentrations than did the age-matched subjects who were not consuming solid foods (P less than or equal to .005). Daily FA1AT excretion, FA1AT concentration, and daily stool output were subsequently determined on a separate group of 40 infants 8 to 12 months of age to ascertain whether differences in total daily FA1AT excretion occur in children fed different types of milk. Total daily FA1AT excretion was similar in the three milk feeding groups. An inverse correlation between FA1AT concentration and daily stool output was also found (P less than .001). The overall rate of detectable [[FH]] in 792 stool smears was 2.1% and unrelated to type of milk feeding. Of 705 stool smears, 3.5% had positive Hematest reactions.(ABSTRACT TRUNCATED AT 250 WORDS)
|mesh-terms=* Aging
* Animals
* Cattle
* Ethnic Groups
* Feces
* Female
* Hemoglobins
* Humans
* Immunodiffusion
* Infant
* Infant Food
* Infant, Newborn
* Male
* Milk
* Milk, Human
* Occult Blood
* Protein-Losing Enteropathies
* alpha 1-Antitrypsin

}}
{{medline-entry
|title=Baroreflex sensitivity and heredity in essential hypertension.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/1735146
|abstract=Abnormalities in baroreflex control of heart rate may be important in the pathogenesis of essential hypertension. To investigate the influence of heredity on baroreflex function, we measured baroreflex sensitivity in 40 untreated patients with essential hypertension grouped by the presence ([[FH]] ) or absence ([[FH]]-) of a family history of hypertension and in 24 normotensive counterparts. Baroreflex sensitivity was assessed by both high-pressure (phenylephrine bolus) and low-pressure (amyl nitrite inhalation) stimuli. Subject groups were matched for age, blood pressure, body weight, and race. Baroreflex sensitivity (in milliseconds per millimeter of mercury) assessed by amyl nitrite inhalation was 24.3 /- 2.8 in [[FH]]- normotensives, 12.3 /- 1.7 in [[FH]] normotensives, 15.4 /- 3.3 in [[FH]]- hypertensives, and 8.1 /- 1.2 in [[FH]] hypertensives. Baroreflex sensitivity assessed by phenylephrine bolus was 28.8 /- 5.6 in [[FH]]- normotensives, 19.3 /- 2.8 in [[FH]] normotensives, 19.1 /- 2.0 in [[FH]]- hypertensives, and 13.6 /- 1.3 in [[FH]] hypertensives. Two-factor analysis of variance showed significant effects on baroreflex sensitivity for blood pressure status (normotensive versus hypertensive) and for family history of hypertension. After control line (controlling) for the effects of several variables, including age, mean arterial pressure, body weight, and race through multiple linear regression analysis, the effect of family history of hypertension on baroreflex sensitivity was still highly significant. Indeed, of all variables investigated, family history of hypertension was the strongest unique baroreflex sensitivity predictor. These data suggest that the impairment in baroreflex sensitivity in hypertension is in part genetically determined and may be an important hereditary component in the pathogenesis of essential hypertension.
|mesh-terms=* Administration, Inhalation
* Adult
* Aging
* Forecasting
* Humans
* Hypertension
* Male
* Middle Aged
* Nitrates
* Pentanols
* Phenylephrine
* Pressoreceptors
* Reflex
* Regression Analysis

|full-text-url=https://sci-hub.do/10.1161/01.cir.85.2.497
}}

FGL2

2021-05-12T15:37:14Z

OdysseusBot: Новая страница: «Fibroleukin precursor (Fibrinogen-like protein 2) (pT49) ==Publications== {{medline-entry |title=Developmental expression of B cell molecules in equine lymphoid...»

Fibroleukin precursor (Fibrinogen-like protein 2) (pT49)

==Publications==

{{medline-entry
|title=Developmental expression of B cell molecules in equine lymphoid tissues.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28063478
|abstract=Identification and classification of B cell subpopulations has been shown to be challenging and inconsistent among different species. Our study tested aspects of ontogeny, phenotype, tissue distribution, and function of equine [[CD5]] B cells, which represented a greater proportion of B cells early in development and in the peritoneal cavity. [[CD5]] and [[CD5]] B cells differentially expressed B cell markers (CD2, CD21, IgM) measured using flow cytometry, but similar mRNA expression of signature genes (DGKA, [[FGL2]], [[PAX5]], [[IGHM]], IL10) measured using quantitative RT-PCR. Sequencing lambda light chain segments revealed that [[CD5]] B cells generated diverse immunoglobulin repertoires, and more frequently bound to fluorescence-labeled phosphorylcholine. This study shows developmental characteristics and tissue distribution of a newly described subpopulation of B cells in the horse.
|mesh-terms=* Aging
* Animals
* B-Lymphocyte Subsets
* B-Lymphocytes
* CD5 Antigens
* Flow Cytometry
* Horses
* Immunoglobulin Light Chains
* Immunophenotyping
* Lymphoid Tissue
* Phosphorylcholine
|keywords=* B cell
* CD5
* Development
* Equine
* Immunoglobulin repertoire
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5267323
}}

FGFR3

2021-05-12T15:37:10Z

OdysseusBot: Новая страница: «Fibroblast growth factor receptor 3 precursor (EC 2.7.10.1) (FGFR-3) (CD333 antigen) [JTK4] ==Publications== {{medline-entry |title=New evidence for positive se...»

Fibroblast growth factor receptor 3 precursor (EC 2.7.10.1) (FGFR-3) (CD333 antigen) [JTK4]

==Publications==

{{medline-entry
|title=New evidence for positive selection helps explain the paternal age effect observed in achondroplasia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23740942
|abstract=There are certain de novo germline mutations associated with genetic disorders whose mutation rates per generation are orders of magnitude higher than the genome average. Moreover, these mutations occur exclusively in the male germ line and older men have a higher probability of having an affected child than younger ones, known as the paternal age effect (PAE). The classic example of a genetic disorder exhibiting a PAE is achondroplasia, caused predominantly by a single-nucleotide substitution (c.1138G>A) in [[FGFR3]]. To elucidate what mechanisms might be driving the high frequency of this mutation in the male germline, we examined the spatial distribution of the c.1138G>A substitution in a testis from an 80-year-old unaffected man. Using a technology based on bead-emulsion amplification, we were able to measure mutation frequencies in 192 individual pieces of the dissected testis with a false-positive rate lower than 2.7 × 10(-6). We observed that most mutations are clustered in a few pieces with 95% of all mutations occurring in 27% of the total testis. Using computational simulations, we rejected the model proposing an elevated mutation rate per cell division at this nucleotide site. Instead, we determined that the observed mutation distribution fits a germline selection model, where mutant spermatogonial stem cells have a proliferative advantage over unmutated cells. Combined with data on several other PAE mutations, our results support the idea that the PAE, associated with a number of Mendelian disorders, may be explained primarily by a selective mechanism.
|mesh-terms=* Achondroplasia
* Aged, 80 and over
* Aging
* Computer Simulation
* Germ-Line Mutation
* Humans
* Male
* Models, Genetic
* Paternal Age
* Polymorphism, Single Nucleotide
* Receptor, Fibroblast Growth Factor, Type 3
* Selection, Genetic
* Spermatogonia
* Testis

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781639
}}
{{medline-entry
|title=Opposite-sex housing reactivates the declining GnRH system in aged transgenic male mice with FGF signaling deficiency.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23047985
|abstract=The continued presence of gonadotropin-releasing hormone (GnRH) neurons is required for a healthy reproductive lifespan, but factors that maintain postnatal GnRH neurons have not been identified. To begin to understand these factors, we investigated whether 1) fibroblast growth factor (FGF) signaling and 2) interactions with the opposite sex are involved in the maintenance of the postnatal GnRH system. A transgenic mouse model (dnFGFR mouse) with the targeted expression of a dominant-negative FGF receptor (dnFGFR) in GnRH neurons was used to examine the consequence of FGF signaling deficiency on postnatal GnRH neurons. Male dnFGFR mice suffered a significant loss of postnatal GnRH neurons within the first 100 days of life. Interestingly, this loss was reversed after cohabitation with female, but not male, mice for 300-550 days. Along with a rescue in GnRH neuron numbers, opposite-sex housing in dnFGFR males also increased hypothalamic GnRH peptide levels, promoted a more mature GnRH neuronal morphology, facilitated litter production, and enhanced testicular morphology. Last, mice hypomorphic for [[FGFR3]] exhibited a similar pattern of postnatal GnRH neuronal loss as dnFGFR males, suggesting FGF signaling acts, in part, through [[FGFR3]] to enhance the maintenance of the postnatal GnRH system. In summary, we have shown that FGF signaling is required for the continued presence of postnatal GnRH neurons. However, this requirement is not absolute, since sexual interactions can compensate for defects in FGFR signaling, thereby rescuing the declining GnRH system. This suggests the postnatal GnRH system is highly plastic and capable of responding to environmental stimuli throughout adult life.
|mesh-terms=* Aging
* Animals
* Cell Count
* Fibroblast Growth Factor 3
* Gonadotropin-Releasing Hormone
* Heterozygote
* Hypothalamus
* Male
* Mice
* Mice, Knockout
* Mice, Transgenic
* Nerve Degeneration
* Nerve Tissue Proteins
* Neurons
* Receptor, Fibroblast Growth Factor, Type 3
* Receptors, LHRH
* Sexual Behavior, Animal
* Signal Transduction
* Synaptic Transmission
* Testis

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532464
}}
{{medline-entry
|title=Intraventricular injection of FGF-2 promotes generation of oligodendrocyte-lineage cells in the postnatal and adult forebrain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22951928
|abstract=[[FGF2]] is considered a key factor in the generation of oligodendrocytes (OLs) derived from neural stem cells (NSCs) located within the subventricular zone (SVZ). Here, we have examined [[FGF2]] signaling in the forebrain of postnatal and adult mice. Using qPCR of microdissected microdomains of the dorsal SVZ (dSVZ) and lateral SVZ (lSVZ), and prominin1-sorted NSCs purified from these microdomains, we show that transcripts for FGF receptor 1 (FGFR1) and [[FGFR2]] are enriched in the dSVZ, from which OLs are largely derived, whereas [[FGFR3]] are significantly enriched within prominen1-sorted NSC of the lSVZ, which mainly generate olfactory interneurons. We show that direct administration of [[FGF2]] into the lateral ventricle increased the generation of oligodendrocyte progenitors (OPCs) throughout the SVZ, both within the dSVZ and ectopically in the lSVZ and ependymal wall of the SVZ. Furthermore, [[FGF2]] stimulated proliferation of neural progenitors (NPs) and their differentiation into OPCs. The results indicate that [[FGF2]] increased specification of OPCs, inducing NPs to follow an oligodendrocyte developmental pathway. Notably, [[FGF2]] did not block OPC differentiation and increased the number of oligodendrocytes in the periventricular white matter (PVWM) and cortex. However, [[FGF2]] markedly disrupted myelination in the PVWM. A key finding was that [[FGF2]] had equivalent actions on the generation of OPCs and myelin disruption in postnatal and adult mice. This study demonstrates a central role for [[FGF2]] in promoting oligodendrocyte generation in the developing and adult brain.
|mesh-terms=* Age Factors
* Aging
* Animals
* Animals, Newborn
* Cell Lineage
* Cerebral Ventricles
* Fibroblast Growth Factor 2
* Injections, Intraventricular
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Neurogenesis
* Oligodendroglia
* Prosencephalon

|full-text-url=https://sci-hub.do/10.1002/glia.22413
}}
{{medline-entry
|title=[[FGFR3]] is a negative regulator of the expansion of pancreatic epithelial cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17192470
|abstract=Fibroblast growth factors (FGFs) and their receptors (FGFRs) are key signaling molecules for pancreas development. Although [[FGFR3]] is a crucial developmental gene, acting as a negative regulator of bone formation, its participation remains unexplored in pancreatic organogenesis. We found that [[FGFR3]] was expressed in the epithelia in both mouse embryonic and adult regenerating pancreata but was absent in normal adult islets. In [[FGFR3]] knockout mice, we observed an increase in the proliferation of epithelial cells in neonates, leading to a marked increase in islet areas in adults. In vitro studies showed that [[FGF9]] is a very potent ligand for [[FGFR3]] and activates extracellular signal-related kinases (ERKs) in pancreatic cell lines. Moreover, [[FGFR3]] blockade or [[FGFR3]] deficiency led to increased proliferation of pancreatic epithelial cells in vivo. This was accompanied by an increase in the proportion of potential islet progenitor cells. Thus, our results show that [[FGFR3]] signaling inhibits the expansion of the immature pancreatic epithelium. Consequently, this study suggests that [[FGFR3]] participates in regulating pancreatic growth during the emergence of mature islet cells.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Cell Line
* Epithelial Cells
* Islets of Langerhans
* Mice
* Mice, Inbred NOD
* Mice, Knockout
* Pancreas
* Receptor, Fibroblast Growth Factor, Type 3
* Regeneration
* Signal Transduction

|full-text-url=https://sci-hub.do/10.2337/db05-1073
}}
{{medline-entry
|title=Enhanced skeletal growth of sheep heterozygous for an inactivated fibroblast growth factor receptor 3.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17032787
|abstract=Normal fibroblast growth factor receptor 3 ([[FGFR3]]) acts as a negative bone growth regulator by restricting chondrocyte proliferation and endochondral bone elongation. In sheep, a heritable mutation that inactivates [[FGFR3]] produces skeletal overgrowth when homozygous, this condition is commonly referred to as spider lamb syndrome (SLS). We hypothesized that sheep heterozygous for the inactivated [[FGFR3]] mutation ([[FGFR3]](SLS/ )) would exhibit enhanced long bone growth and greater frame size; additionally, the isolated effects of increased bone growth would translate into greater BW and larger LM area relative to normal lambs at harvest. The current study investigated bone length and LM area of [[FGFR3]](SLS/ ) sheep at maturity and during growth. At maturity, [[FGFR3]](SLS/ ) ewes exhibited a larger frame size and longer bones than normal [[FGFR3]]( / ) ewes (P < 0.05). Similarly, [[FGFR3]](SLS/ ) lambs had greater frame sizes than normal [[FGFR3]]( / ) lambs, as indicated by increased metacarpal III length and height at withers (P < 0.05). The [[FGFR3]](SLS/ ) lambs took longer than the normal [[FGFR3]]( / ) lambs to reach the 60-kg common BW harvest end point (P < 0.05). The [[FGFR3]](SLS/ ) lambs showed no difference in BW, ADG, or LM area at any age compared with normal [[FGFR3]]( / ) lambs (P > 0.2). A similar LM area produced in the context of a greater frame size and skeletal length produces a greater muscle volume, thereby potentially increasing meat yield. The results of this study suggest that [[FGFR3]](SLS/ ) animals exhibit a relaxation of the normal inhibition of chondrocyte proliferation, resulting in an increase in the overall frame size. The sheep industry could utilize the naturally occurring genetic mutation in [[FGFR3]] to potentially increase meat yields with enhanced skeletal growth as an alternative to exogenous growth promotants.
|mesh-terms=* Aging
* Animals
* Body Composition
* Bone Development
* Female
* Heterozygote
* Male
* Receptor, Fibroblast Growth Factor, Type 3
* Sheep

|full-text-url=https://sci-hub.do/10.2527/jas.2006-255
}}
{{medline-entry
|title=Expression and possible function of fibroblast growth factor 9 ([[FGF9]]) and its cognate receptors [[FGFR2]] and [[FGFR3]] in postnatal and adult retina.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15614790
|abstract=Fibroblast growth factors (FGFs) are important regulators of retinal development and survival. We examined the expression and distribution of [[FGF9]] and its preferred receptors [[FGFR2]]IIIc and [[FGFR3]]IIIc in this tissue. [[FGF9]] transcripts in whole rat retina were detected by RT-PCR but were not present in purified cultured Muller glia. Transcripts appeared as 3.2-kb and 4.0-kb bands on Northern blots, and Western blotting of whole retina revealed [[FGF9]]-immunoreactive bands at 30 and 55 kDa. [[FGF9]] mRNA demonstrated a biphasic expression profile, elevated at birth and adulthood, but relatively decreased during terminal retinal differentiation (4-14 days postnatal). Antibody labeling broadly reflected these findings: staining in vivo was observed mainly in the inner retina (and outer plexiform layer in adults) whereas [[FGF9]] was not detectable in cultured Muller glia. In adults, [[FGF9]] in situ hybridization also showed a detectable signal in inner retina. [[FGFR2]]IIIc and [[FGFR3]]IIIc were detected by RT-PCR, and Western blotting showed both FGFRs existed as multiple forms between approximately 100-200 kDa. [[FGFR2]] and [[FGFR3]] antibodies showed prominent labeling in the inner retina, especially in proliferating cultured Muller glia. Exogenous [[FGF9]] elicited a dose-dependent increase in Muller glial proliferation in vitro. These data suggest a role for [[FGF9]] in retinal differentiation and maturation, possibly representing a neuronally derived factor acting upon glial (and other) cells.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Cell Differentiation
* Cell Proliferation
* Dose-Response Relationship, Drug
* Fibroblast Growth Factor 9
* Fibroblast Growth Factors
* Gene Expression Regulation, Developmental
* Neuroglia
* Neurons
* Protein Isoforms
* Protein-Tyrosine Kinases
* RNA, Messenger
* Rats
* Rats, Wistar
* Receptor Protein-Tyrosine Kinases
* Receptor, Fibroblast Growth Factor, Type 2
* Receptor, Fibroblast Growth Factor, Type 3
* Receptors, Fibroblast Growth Factor
* Retina

|full-text-url=https://sci-hub.do/10.1002/jnr.20363
}}
{{medline-entry
|title=Negative autoregulation of fibroblast growth factor receptor 2 expression characterizing cranial development in cases of Apert (P253R mutation) and Pfeiffer (C278F mutation) syndromes and suggesting a basis for differences in their cranial phenotypes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11596961
|abstract=Heterogeneous mutations in the fibroblast growth factor receptor 2 gene ([[FGFR2]]) cause a range of craniosynostosis syndromes. The specificity of the Apert syndrome-affected cranial phenotype reflects its narrow mutational range: 98% of cases of Apert syndrome result from an Ser252Trp or Pro253Arg mutation in the immunoglobulin-like (Ig)IIIa extracellular subdomain of [[FGFR2]]. In contrast, a broad range of mutations throughout the extracellular domain of [[FGFR2]] causes the overlapping cranial phenotypes of Pfeiffer and Crouzon syndromes and related craniofacial dysostoses. In this paper the expression of [[FGFR1]], the IgIIIa/c and IgIIIa/b isoforms of [[FGFR2]], and [[FGFR3]] is investigated in Apert syndrome (P253R mutation)- and Pfeiffer syndrome (C278F mutation)-affected fetal cranial tissue and is contrasted with healthy human control tissues. Both [[FGFR1]] and [[FGFR3]] are normally expressed in the differentiated osteoblasts of the periosteum and osteoid, in domains overlapped by that of [[FGFR2]], which widely include preosseous cranial mesenchyme. Expression of [[FGFR2]], however, is restricted to domains of advanced osseous differentiation in both Apert syndrome- and Pfeiffer syndrome-affected cranial skeletogenesis in the presence of fibroblast growth factor (FGF)2, but not in the presence of [[FGF4]] or [[FGF7]]. Whereas expression of the [[FGFR2]]-IgIIIa/b (KGFR) isoform is restricted in normal human cranial osteogenesis, there is preliminary evidence that KGFR is ectopically expressed in Pfeiffer syndrome-affected cranial osteogenesis. Contraction of the [[FGFR2]]-IgIIIa/c (BEK) expression domain in cases of Apert syndrome- and Pfeiffer syndrome-affected fetal cranial ossification suggests that the mutant activation of this receptor, by ligand-dependent or ligand-independent means, results in negative autoregulation. This phenomenon, resulting from different mechanisms in the two syndromes, offers a model by which to explain differences in their cranial phenotypes.
|mesh-terms=* Acrocephalosyndactylia
* Aging
* Embryonic and Fetal Development
* Fetus
* Homeostasis
* Humans
* Infant
* Mutation
* Osteogenesis
* Phenotype
* Receptor Protein-Tyrosine Kinases
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Receptors, Fibroblast Growth Factor
* Skull

|full-text-url=https://sci-hub.do/10.3171/jns.2001.95.4.0660
}}
{{medline-entry
|title=Markers for bone metabolism in a long-lived case of thanatophoric dysplasia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10890204
|abstract=We report a male patient with type 1 thanatophoric dysplasia, now eight years old, having a mutation in the [[FGFR3]] gene. Radiological examination at birth revealed that the ribs and the bones of the extremities were very short and vertebral bodies were greatly reduced in height with wide intervertebral spaces. The femurs were shaped like French telephone receivers. Because of respiratory insufficiency due to the narrow thorax, the patient has been intubated and supported by continuous mechanical ventilation since the day after birth. Since 5 years of age, despite sufficient caloric intake, his body weight never increased above 4700 g, body height 49.0 cm, head circumference 46.1 cm, and chest circumference 35.8 cm. Acanthosis nigricance and huge bilateral coral-like urolithiases has been present. His mental development was severely retarded but he was able to make emotional expressions. Although developments in motor functions could not be assessed, his neurodevelopmental milestones in social relationships and language perception seemed to be at the level of a 10 to 12 month old. His bone maturation was also severely retarded. All of the assays of his serum and urinary bone formation- or resorption-related substances were within normal limits for age. Therefore, bone formation as well as bone resorption activities seemed normal and not responsible for his growth retardation.
|mesh-terms=* Biomarkers
* Bone and Bones
* Child
* Child Development
* Humans
* Longevity
* Male
* Mutation, Missense
* Protein-Tyrosine Kinases
* Radiography
* Receptor, Fibroblast Growth Factor, Type 3
* Receptors, Fibroblast Growth Factor
* Thanatophoric Dysplasia

|full-text-url=https://sci-hub.do/10.1507/endocrj.47.supplmarch_s141
}}

FGFR2

2021-05-12T15:37:08Z

OdysseusBot: Новая страница: «Fibroblast growth factor receptor 2 precursor (EC 2.7.10.1) (FGFR-2) (K-sam) (KGFR) (Keratinocyte growth factor receptor) (CD332 antigen) [BEK] [KGFR] [KSAM] ==P...»

Fibroblast growth factor receptor 2 precursor (EC 2.7.10.1) (FGFR-2) (K-sam) (KGFR) (Keratinocyte growth factor receptor) (CD332 antigen) [BEK] [KGFR] [KSAM]

==Publications==

{{medline-entry
|title=Oncogenic mutations in histologically normal endometrium: the new normal?
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31187483
|abstract=The advent of next generation sequencing has vastly improved the resolution of mutation detection, thereby both increasing the resolution of the analysis of cancer tissues and shining light on the existence of somatic driver mutations in normal tissues, even in the absence of cancer. Studies have described somatic driver mutations in normal skin, blood, peritoneal washings, and esophageal epithelium. Such findings prompt speculation on whether such mutations exist in other tissues, such as the eutopic endometrium in particular, due to the highly regenerative nature of the endometrium and the recent observation of recurrent somatic driver mutations in deep infiltrating and iatrogenic endometriosis (tissues believed to be derived from the eutopic endometrium) by our group and others. In the current study we investigated the presence of somatic driver mutations in histologically normal endometrium from women lacking evidence of gynecologic malignancy or endometrial hyperplasia. Twenty-five women who underwent hysterectomies and 85 women who underwent endometrial biopsies were included in this study. Formalin-fixed, paraffin-embedded tissue specimens were analyzed by means of targeted sequencing followed by orthogonal validation with droplet digital PCR. [[PTEN]] and [[ARID1A]] immunohistochemistry (IHC) was also performed as surrogates for inactivating mutations in the respective genes. Overall, we observed somatic driver-like events in over 50% of normal endometrial samples analyzed, including hotspot mutations in [[KRAS]], [[PIK3CA]], and [[FGFR2]] as well as [[PTEN]]-loss by IHC. Analysis of anterior and posterior samplings collected from women who underwent hysterectomies was consistent with the presence of somatic driver mutations within clonal pockets spread throughout the uterus. The prevalence of such oncogenic mutations also increased with age (OR: 1.05 [95% CI: 1.00-1.10], p = 0.035). These findings have implications on our understanding of aging and so-called 'normal tissues', thereby necessitating caution in the utilization of mutation-based early detection tools for endometrial or other cancers. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley

FGFR1

2021-05-12T15:37:05Z

OdysseusBot: Новая страница: «Fibroblast growth factor receptor 1 precursor (EC 2.7.10.1) (FGFR-1) (Basic fibroblast growth factor receptor 1) (BFGFR) (bFGF-R-1) (Fms-like tyrosine kinase 2) (...»

Fibroblast growth factor receptor 1 precursor (EC 2.7.10.1) (FGFR-1) (Basic fibroblast growth factor receptor 1) (BFGFR) (bFGF-R-1) (Fms-like tyrosine kinase 2) (FLT-2) (N-sam) (Proto-oncogene c-Fgr) (CD331 antigen) [BFGFR] [CEK] [FGFBR] [FLG] [FLT2] [HBGFR]

==Publications==

{{medline-entry
|title=Alignment of Alzheimer's disease amyloid β-peptide and klotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32999998
|abstract=The cause of Alzheimer's disease (AD) is poorly understood. In 1991, the amyloid hypothesis postulated that β-amyloid (Aβ) accumulation is a key element. It follows that clearing the brain of Aβ would be beneficial, which has not been the case. Therefore, Aβ is likely a result, not a cause, of AD and may be protective rather than harmful. The apolipoprotein E4 (apoE4) allele is the strongest genetic risk factor for AD. Klotho ([[KL]]), encoded by the [[KL]] gene, may be another AD-related protein. [[FGF21]] is a circulating endocrine hormone, mainly secreted by the liver, mostly during fasting. [[FGF21]] acts by binding to its receptor [[FGFR1]] and co-receptor β-klotho. [[FGF21]] is neuroprotective and could delay onset of AD. In the present study, the [[KL]] protein structure was examined to determine whether it may interact with Aβ. Protein data bank (pdb) entries for klotho and Aβ were searched on the RCSB Protein Data Bank for β-[[KL]] and AD amyloid β-peptide. The protein structures were superimposed and aligned on PYMOL v2.3.4 with the super command, which super aligns two protein selections. To evaluate the conservation and alignment of the Aβ and [[KL]] genomes across species, BLAT, the Blast-Like Alignment Tool of the UCSC Genome Browser, was used. The amino acid residues phe76-val96 of [[KL]] aligned closely with residues asp7-asn27 of Aβ. Cross-species comparison of [[KL]] revealed a high degree of alignment and conservation in the chimp and 27 other primates; however, less alignment and conservation were observed in the mouse, dog and elephant, even less in the chicken, western clawed frog ([i]Xenopus tropicalis[/i]), zebrafish and lamprey. The current finding of amino acid residues phe76-val96 of klotho aligning closely with residues asp7-asn27 of Aβ suggests that Aβ can enhance the ability of klotho to draw [[FGF21]] to regions of incipient neurodegeneration in AD. The problem arises with age. Older individuals do not heal or repair tissue damage as well as younger individuals. As neurodegeneration advances in an older individual, perhaps caused by neuroinflammation related to herpes simplex virus type 1, increasing amounts of amyloid are produced, forming an adhesive web, as the brain tries to hold the pathologic process in check. Meanwhile, the damage increases and spreads. Progressive neurodegeneration and cognitive decline are the outcome.

|keywords=* Alzheimer’s disease
* HSV-1
* aging
* alignment
* klotho
* neurodegeneration
* neuroinflammation
* protein
* ubiquitin
* β-amyloid
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521834
}}
{{medline-entry
|title=Sulfated syndecan 1 is critical to preventing cellular senescence by modulating fibroblast growth factor receptor endocytosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32530114
|abstract=Cellular senescence can be triggered by various intrinsic and extrinsic stimuli. We previously reported that silencing of 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 ([[PAPSS2]]) induces cellular senescence through augmented fibroblast growth factor receptor 1 ([[FGFR1]]) signaling. However, the exact molecular mechanism connecting heparan sulfation and cellular senescence remains unclear. Here, we investigated the potential involvement of heparan sulfate proteoglycans (HSPGs) in augmented [[FGFR1]] signaling and cellular senescence. Depletion of several types of HSPGs revealed that cells depleted of syndecan 1 ([[SDC1]]) exhibited typical senescence phenotypes, and those depleted of [[PAPSS2]]-, [[SDC1]]-, or heparan sulfate 2-O sulfotransferase 1 (HS2ST1) showed decreased [[FGFR1]] internalization along with hyperresponsiveness to and prolonged activation of fibroblast growth factor 2 (FGF2)-stimulated [[FGFR1]]- v-akt murine thymoma viral oncogene homolog (AKT) signaling. Clathrin- and caveolin-mediated [[FGFR1]] endocytosis contributed to cellular senescence through the [[FGFR1]]-AKT-p53-p21 signaling pathway. Dynasore treatment triggered senescence phenotypes, augmented [[FGFR1]]-AKT-p53-p21 signaling, and decreased [[SDC1]] expression. Finally, the replicatively and prematurely senescent cells were characterized by decreases of [[SDC1]] expression and [[FGFR1]] internalization, and an increase in [[FGFR1]]-AKT-p53-p21 signaling. Together, our results demonstrate that properly sulfated [[SDC1]] plays a critical role in preventing cellular senescence through the regulation of [[FGFR1]] endocytosis.

|keywords=* FGFR1
* SDC1
* cellular senescence
* endocytosis
* heparan sulfation
|full-text-url=https://sci-hub.do/10.1096/fj.201902714R
}}
{{medline-entry
|title=Satellite cell-specific ablation of Cdon impairs integrin activation, FGF signalling, and muscle regeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32103583
|abstract=Perturbation in cell adhesion and growth factor signalling in satellite cells results in decreased muscle regenerative capacity. Cdon (also called Cdo) is a component of cell adhesion complexes implicated in myogenic differentiation, but its role in muscle regeneration remains to be determined. We generated inducible satellite cell-specific Cdon ablation in mice by utilizing a conditional Cdon allele and Pax7 . To induce Cdon ablation, mice were intraperitoneally injected with tamoxifen (tmx). Using cardiotoxin-induced muscle injury, the effect of Cdon depletion on satellite cell function was examined by histochemistry, immunostaining, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Isolated myofibers or myoblasts were utilized to determine stem cell function and senescence. To determine pathways related to Cdon deletion, injured muscles were subjected to RNA sequencing analysis. Satellite cell-specific Cdon ablation causes impaired muscle regeneration with fibrosis, likely attributable to decreased proliferation, and senescence, of satellite cells. Cultured Cdon-depleted myofibers exhibited 32 ± 9.6% of EdU-positive satellite cells compared with 58 ± 4.4% satellite cells in control myofibers (P < 0.05). About 32.5 ± 3.7% Cdon-ablated myoblasts were positive for senescence-associated β-galactosidase (SA-β-gal) while only 3.6 ± 0.5% of control satellite cells were positive (P < 0.001). Transcriptome analysis of muscles at post-injury Day 4 revealed alterations in genes related to mitogen-activated protein kinase signalling (P < 8.29 e ) and extracellular matrix (P < 2.65 e ). Consistent with this, Cdon-depleted tibialis anterior muscles had reduced phosphorylated extracellular signal-regulated kinase (p-ERK) protein levels and expression of ERK targets, such as Fos (0.23-fold) and Egr1 (0.31-fold), relative to mock-treated control muscles (P < 0.001). Cdon-depleted myoblasts exhibited impaired ERK activation in response to basic fibroblast growth factor. Cdon ablation resulted in decreased and/or mislocalized integrin β1 activation in satellite cells (weak or mislocalized integrin1 in tmx = 38.7 ± 1.9%, mock = 21.5 ± 6%, P < 0.05), previously linked with reduced fibroblast growth factor (FGF) responsiveness in aged satellite cells. In mechanistic studies, Cdon interacted with and regulated cell surface localization of [[FGFR1]] and [[FGFR4]], likely contributing to FGF responsiveness of satellite cells. Satellite cells from a progeria model, Zmpste24 myofibers, showed decreased Cdon levels (Cdon-positive cells in Zmpste24 = 63.3 ± 11%, wild type = 90 ± 7.7%, P < 0.05) and integrin β1 activation (weak or mislocalized integrin β1 in Zmpste24 = 64 ± 6.9%, wild type = 17.4 ± 5.9%, P < 0.01). Cdon deficiency in satellite cells causes impaired proliferation of satellite cells and muscle regeneration via aberrant integrin and FGFR signalling.

|keywords=* Cdon
* Cellular senescence
* FGFR
* Growth factor signalling
* Muscle regeneration
* Satellite cell
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432598
}}
{{medline-entry
|title=The influence of fibroblast growth factor 2 on the senescence of human adipose-derived mesenchymal stem cells during long-term culture.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31840944
|abstract=Adipose-derived mesenchymal stem cells (ASCs) exhibit great potential in regenerative medicine, and in vitro expansion is frequently necessary to obtain a sufficient number of ASCs for clinical use. Fibroblast growth factor 2 ([[FGF2]]) is a common supplement in the ASC culture medium to enhance cell proliferation. To achieve clinical applicability of ASC-based products, prolonged culture of ASCs is sometimes required to obtain sufficient quantity of ASCs. However, the effect of [[FGF2]] on ASCs during prolonged culture has not been previously determined. In this study, ASCs were subjected to prolonged in vitro culture with or without [[FGF2]]. [[FGF2]] maintained the small cell morphology and expedited proliferation kinetics in early ASC passages. After prolonged in vitro expansion, [[FGF2]]-treated ASCs exhibited increased cell size, arrested cell proliferation, and increased cellular senescence relative to the control ASCs. We observed an upregulation of [[FGFR1]]c and enhanced expression of downstream [[STAT3]] in the initial passages of [[FGF2]]-treated ASCs. The application of an [[FGFR1]] or [[STAT3]] inhibitor effectively blocked the enhanced proliferation of ASCs induced by [[FGF2]] treatment. [[FGFR1]]c upregulation and enhanced [[STAT3]] expression were lost in the later passages of [[FGF2]]-treated ASCs, suggesting that the continuous stimulation of [[FGF2]] becomes ineffective because of the refractory downstream [[FGFR1]] and the [[STAT3]] signaling pathway. In addition, no evidence of tumorigenicity was noted in vitro and in vivo after prolonged expansion of [[FGF2]]-cultured ASCs. Our data indicate that ASCs have evolved a [[STAT3]]-dependent response to continuous [[FGF2]] stimulation which promotes the initial expansion but limits their long-term proliferation.

|keywords=* cell proliferation
* cellular senescence
* fibroblast growth factor 2
* long-term culture
* mesenchymal stem cell
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103622
}}
{{medline-entry
|title=Systemic administration of a fibroblast growth factor receptor 1 agonist rescues the cognitive deficit in aged socially isolated rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30928883
|abstract=Social isolation predominantly occurs in elderly people and it is strongly associated with cognitive decline. However, the mechanisms that produce isolation-related cognitive dysfunction during aging remain unclear. Here, we evaluated the cognitive, electrophysiological, and morphological effects of short- (4 weeks) and long-term (12 weeks) social isolation in aged male Wistar rats. Long-term but not short-term social isolation increased the plasma corticosterone levels and impaired spatial memory in the Morris water maze. Moreover, isolated animals displayed dampened hippocampal long-term potentiation in vivo, both in the dentate gyrus (DG) and [[CA1]], as well as a specific reduction in the volume of the stratum oriens and spine density in [[CA1]]. Interestingly, social isolation induced a transient increase in hippocampal basic fibroblast growth factor (FGF2), whereas fibroblast growth factor receptor 1 ([[FGFR1]]) levels only increased after long-term isolation. Importantly, subchronic systemic administration of FGL, a synthetic peptide that activates [[FGFR1]], rescued spatial memory in long-term isolated rats. These findings provide new insights into the neurobiological mechanisms underlying the detrimental effects on memory of chronic social isolation in the aged.
|mesh-terms=* Aging
* Animals
* Cognition
* Cognitive Dysfunction
* Corticosterone
* Fibroblast Growth Factor 2
* Hippocampus
* Long-Term Potentiation
* Male
* Maze Learning
* Peptides
* Rats, Wistar
* Receptor, Fibroblast Growth Factor, Type 1
* Social Isolation
* Spatial Memory
* Time Factors
|keywords=* Cognition
* Corticosterone
* FGF
* Hippocampus
* LTP
* Stress
|full-text-url=https://sci-hub.do/10.1016/j.neurobiolaging.2019.02.011
}}
{{medline-entry
|title=Impact of aging and caloric restriction on fibroblast growth factor 21 signaling in rat white adipose tissue.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30620889
|abstract=Caloric restriction (CR) suppresses age-related pathophysiology and extends lifespan. We recently reported that metabolic remodeling of white adipose tissue (WAT) plays an important role in the beneficial actions of CR; however, the detailed molecular mechanisms of this remodeling remain to be established. In the present study, we aimed to identify CR-induced alterations in the expression of fibroblast growth factor 21 ([[FGF21]]), a regulator of lipid and glucose metabolism, and of its downstream signaling mediators in liver and WAT, across the lifespan of rats. We evaluated groups of rats that had been either fed ad libitum or calorie restricted from 3 months of age and were euthanized at 3.5, 9, or 24 months of age, under fed and fasted conditions. The expression of [[FGF21]] mRNA and/or protein increased with age in liver and WAT. Interestingly, in the WAT of 9-month-old fed rats, CR further upregulated [[FGF21]] expression and eliminated the aging-associated reductions in the expression of [[FGFR1]] and beta-klotho (KLB; [[FGF21]] receptor complex). It also enhanced the expression of [[FGF21]] targets, including glucose transporter 1 and peroxisome proliferator-activated receptor (PPAR)γ coactivator-1α. The analysis of transcriptional regulators of Fgf21 suggested that aging and CR might upregulate Fgf21 expression via different mechanisms. In adipocytes in vitro, constitutive [[FGF21]] overexpression upregulated the [[FGF21]] receptor complex and [[FGF21]] targets at the mRNA or protein level. Thus, both aging and CR induced [[FGF21]] expression in rat WAT; however, only CR activated [[FGF21]] signaling. Our results suggest that [[FGF21]] signaling contributes to the CR-induced metabolic remodeling of WAT, likely activating glucose uptake and mitochondrial biogenesis.
|mesh-terms=* 3T3-L1 Cells
* Adipose Tissue, White
* Aging
* Animals
* Caloric Restriction
* Fibroblast Growth Factors
* Glucose Transporter Type 1
* Male
* Mice
* Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
* Rats
* Rats, Wistar
* Signal Transduction
|keywords=* Caloric restriction
* Fibroblast growth factor 21
* Glucose transporter 1
* White adipose tissue
* β-Klotho
|full-text-url=https://sci-hub.do/10.1016/j.exger.2019.01.001
}}
{{medline-entry
|title=Activity-dependent neuronal Klotho enhances astrocytic aerobic glycolysis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29493420
|abstract=Mutations of the β-glucuronidase protein α-Klotho have been associated with premature aging, and altered cognitive function. Although highly expressed in specific areas of the brain, Klotho functions in the central nervous system remain unknown. Here, we show that cultured hippocampal neurons respond to insulin and glutamate stimulation by elevating Klotho protein levels. Conversely, AMPA and NMDA antagonism suppress neuronal Klotho expression. We also provide evidence that soluble Klotho enhances astrocytic aerobic glycolysis by hindering pyruvate metabolism through the mitochondria, and stimulating its processing by lactate dehydrogenase. Pharmacological inhibition of [[FGFR1]], Erk phosphorylation, and monocarboxylic acid transporters prevents Klotho-induced lactate release from astrocytes. Taken together, these data suggest Klotho is a potential new player in the metabolic coupling between neurons and astrocytes. Neuronal glutamatergic activity and insulin modulation elicit Klotho release, which in turn stimulates astrocytic lactate formation and release. Lactate can then be used by neurons and other cells types as a metabolic substrate.
|mesh-terms=* Animals
* Astrocytes
* Brain
* Energy Metabolism
* Glucuronidase
* Glycolysis
* Mice
* Mice, Inbred C57BL
* Neurons
* Oxygen
|keywords=* Energy metabolism
* aging
* astrocytes
* lactate
* neuronal-glial interaction
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681535
}}
{{medline-entry
|title=Decline in Proliferation and Immature Neuron Markers in the Human Subependymal Zone during Aging: Relationship to [[EGF]]- and FGF-Related Transcripts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27932973
|abstract=Neuroblasts exist within the human subependymal zone (SEZ); however, it is debated to what extent neurogenesis changes during normal aging. It is also unknown how precursor proliferation may correlate with the generation of neuronal and glial cells or how expression of growth factors and receptors may change throughout the adult lifespan. We found evidence of dividing cells in the human SEZ (n D 50) in conjunction with a dramatic age-related decline (21-103 years) of mRNAs indicative of proliferating cells (Ki67) and immature neurons (doublecortin). Microglia mRNA (ionized calcium-binding adapter molecule 1) increased during aging, whereas transcript levels of stem/precursor cells (glial fibrillary acidic protein delta and achaete-scute homolog 1), astrocytes (vimentin and pan-glial fibrillary acidic protein), and oligodendrocytes (oligodendrocyte lineage transcription factor 2) remained stable. Epidermal growth factor receptor ([[EGF]]R) and fibroblast growth factor 2 ([[FGF2]]) mRNAs increased throughout adulthood, while transforming growth factor alpha (TGFα), [[EGF]], Erb-B2 receptor tyrosine kinase 4 (ErbB4) and FGF receptor 1 ([[FGFR1]]) mRNAs were unchanged across adulthood. Cell proliferation mRNA positively correlated with [[FGFR1]] transcripts. Immature neuron and oligodendrocyte marker expression positively correlated with TGFα and ErbB4 mRNAs, whilst astrocyte transcripts positively correlated with [[EGF]], [[FGF2]], and [[FGFR1]] mRNAs. Microglia mRNA positively correlated with [[EGF]] and [[FGF2]] expression. Our findings indicate that neurogenesis in the human SEZ continues well into adulthood, although proliferation and neuronal differentiation may decline across adulthood. We suggest that mRNA expression of [[EGF]]- and FGF-related family members do not become limited during aging and may modulate neuronal and glial fate determination in the SEZ throughout human life.

|keywords=* aging
* doublecortin
* gliogenesis
* human
* neurogenesis
* proliferation
* subventricular zone
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123444
}}
{{medline-entry
|title=Age-Related Changes in FGF-2, Fibroblast Growth Factor Receptors and β-Catenin Expression in Human Mesenchyme-Derived Progenitor Cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26332075
|abstract=FGF-2 stimulates preosteoblast replication, and knockout of the FGF-2 gene in mice resulted in osteopenia with age, associated with decreased Wnt-β-Catenin signaling. In addition, targeted expression of FGF-2 in osteoblast progenitors increased bone mass in mice via Wnt-β-Catenin signaling. We posited that diminution of the intrinsic proliferative capacity of human mesenchyme-derived progenitor cells (HMDPCs) with age is due in part to reduction in FGF-2. To test this hypothesis HMDPCs from young (27-38), middle aged (47-56), and old (65-76) female human subjects were isolated from bone discarded after orthopedic procedures. HMDPCs cultures were mostly homogeneous with greater than 90% mesenchymal progenitor cells, determined by fluorescence-activated cell sorting. There was a progressive decrease in FGF-2 and [[FGFR1]] mRNA and protein in HMDPCs with age. Since FGF-2 activates β-catenin, which can enhance bone formation, we also assessed its age-related expression in HMDPCs. An age-related decrease in total-β-Catenin mRNA and protein expression was observed. However there were increased levels of p-β-Catenin and decreased levels of activated-β-Catenin in old HMDSCs. FGF-2 treatment increased [[FGFR1]] and β-Catenin protein, reduced the level of p-β-Catenin and increased activated-β-Catenin in aged HMDPCs. In conclusion, reduction in FGF-2 expression could contribute to age-related impaired function of HMDPCs via modulation of Wnt-β-catenin signaling.
|mesh-terms=* Adult
* Aged
* Aging
* Cells, Cultured
* Female
* Fibroblast Growth Factor 2
* Gene Expression
* Humans
* Mesenchymal Stem Cells
* Middle Aged
* Receptor, Fibroblast Growth Factor, Type 1
* Wnt Signaling Pathway
* Young Adult
* beta Catenin
|keywords=* AGING
* ENDOGENOUS FIBROBLAST GROWTH FACTOR-2
* FIBROBLAST GROWTH FACTOR RECEPTOR
* HUMAN MESENCHYME-DERIVED PROGENITOR CELLS
* β-CATENIN
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861164
}}
{{medline-entry
|title=A correlation between decreased parathyroid α-Klotho and fibroblast growth factor receptor 1 expression with pathological category and parathyroid gland volume in dialysis patients.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25749987
|abstract=The objective of this study was to investigate α-Klotho and fibroblast growth factor receptor 1 ([[FGFR1]]) expression in hyperplastic parathyroid glands, as well as their role in the development of renal hyperparathyroidism. Hyperplastic parathyroid glands (n = 90) were obtained from 24 patients who received parathyroidectomy due to secondary renal hyperparathyroidism. Normal parathyroid tissue was obtained from glands (n = 6) that were inadvertently removed, in conjunction with thyroidectomy, from patients with thyroid carcinoma. The expression of α-Klotho and [[FGFR1]] in the parathyroid tissue was detected using immunohistochemical staining. The expression of α-Klotho and [[FGFR1]] was significantly reduced in the hyperplastic parathyroid tissue compared to that in the normal parathyroid tissue. The expression of α-Klotho decreased further with increasing parathyroid pathology. A significant positive correlation was observed between α-Klotho and [[FGFR1]] (r = 0.38, P < 0.01). [[FGFR1]] (r = -0.21, P < 0.05) and α-Klotho (r = -0.42, P < 0.01) were negatively correlated with the volume of the hyperplastic parathyroid tissue. The expression of α-Klotho and [[FGFR1]] decreases in the parathyroid glands of dialysis patients with secondary hyperparathyroidism, and this decrease may play an important role in the pathogenesis of secondary renal hyperparathyroidism.
|mesh-terms=* Adult
* Aged
* Aging
* Female
* Follow-Up Studies
* Glucuronidase
* Humans
* Hyperparathyroidism, Secondary
* Hyperplasia
* Immunohistochemistry
* Kidney Failure, Chronic
* Male
* Middle Aged
* Parathyroid Glands
* Receptor, Fibroblast Growth Factor, Type 1
* Renal Dialysis
* Retrospective Studies
* Time Factors

|full-text-url=https://sci-hub.do/10.1007/s11255-015-0917-0
}}
{{medline-entry
|title=A molecular signature predictive of indolent prostate cancer.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24027026
|abstract=Many newly diagnosed prostate cancers present as low Gleason score tumors that require no treatment intervention. Distinguishing the many indolent tumors from the minority of lethal ones remains a major clinical challenge. We now show that low Gleason score prostate tumors can be distinguished as indolent and aggressive subgroups on the basis of their expression of genes associated with aging and senescence. Using gene set enrichment analysis, we identified a 19-gene signature enriched in indolent prostate tumors. We then further classified this signature with a decision tree learning model to identify three genes--[[FGFR1]], [[PMP22]], and [[CDKN1A]]--that together accurately predicted outcome of low Gleason score tumors. Validation of this three-gene panel on independent cohorts confirmed its independent prognostic value as well as its ability to improve prognosis with currently used clinical nomograms. Furthermore, protein expression of this three-gene panel in biopsy samples distinguished Gleason 6 patients who failed surveillance over a 10-year period. We propose that this signature may be incorporated into prognostic assays for monitoring patients on active surveillance to facilitate appropriate courses of treatment.
|mesh-terms=* Aged
* Aging
* Animals
* Biomarkers, Tumor
* Decision Trees
* Gene Expression Profiling
* Gene Expression Regulation, Neoplastic
* Genes, Neoplasm
* Humans
* Male
* Mice
* Middle Aged
* Models, Biological
* Prognosis
* Prostatic Neoplasms
* RNA, Messenger
* Reproducibility of Results
* Species Specificity

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943244
}}
{{medline-entry
|title=[Pulmonary expression levels of fibroblast growth factor receptors and lung fibrosis in mice at different ages].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23644131
|abstract=To explore the correlation of pulmonary expressions of fibroblast growth factor receptors ([[FGFR1]]-4) with lung fibrosis and aging. Real-time fluorescence quantitative PCR was used to detect the expression levels of [[FGFR1]]-4 in the lung tissues, and lung fibrosis was observed by HE and Masson staining in mice at different ages. The 4 subtypes of FGFR showed different expression levels in the lung tissues of mice, and [[FGFR2]] had the highest expressions. The expression levels of all the 4 FGFR subtypes in 8-month-old mice were significantly lower than those in 5-week-old mice. The 8-month-old mice tended to present with histological changes of lung fibrosis. FGFR expressions is down-regulated with aging in mice. Among the FGFR subtypes, [[FGFR2]] is expressed at the highest level. The occurrence of lung fibrosis with aging is probably associated with down-regulated FGFR expression. FGF/FGFR signaling may participate in the aging process and regulation of lung fibrosis.
|mesh-terms=* Aging
* Animals
* Lung
* Male
* Mice
* Mice, Inbred C57BL
* Pulmonary Fibrosis
* Receptors, Fibroblast Growth Factor
* Signal Transduction

}}
{{medline-entry
|title=Inhibition of fibroblast growth factor receptor 1 endocytosis promotes axonal branching of adult sensory neurons.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21575685
|abstract=Fibroblast growth factors (FGFs) promote axon growth during development and regeneration of the nervous system. Among the four types of FGF receptors (FGFRs), [[FGFR1]] is expressed in adult sensory neurons of dorsal root ganglia (DRG), and overexpression of [[FGFR1]] promotes FGF-2-induced elongative axon growth in vitro. Ligand-induced activation of [[FGFR1]] is followed by endocytosis and lysosomal degradation, which leads to the termination of receptor signaling. We previously reported that the lysosomal inhibitor leupeptin enhances FGF-2-induced elongative axon growth of adult DRG neurons overexpressing [[FGFR1]]. To better understand the role of subcellular localization of [[FGFR1]] in axon growth, we analyzed the effects of inhibition of endocytosis of [[FGFR1]] on FGF-2-induced neurite outgrowth in PC12 pheochromocytoma cells and adult DRG neurons. The endocytosis inhibitors methyl-β-cyclodextrin (MβCD) and chlorpromazine enhanced surface localization of [[FGFR1]] in PC12 cells and DRG neurons. Furthermore, MβCD and chlorpromazine increased FGF-2-induced neurite outgrowth of PC12 cells and axonal branching of adult DRG neurons overexpressing [[FGFR1]], whereas MβCD inhibited FGF-2-induced axonal elongation. Analysis of the signaling pathways involved in axon morphology revealed that FGF-2-induced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was increased by inhibition of [[FGFR1]] endocytosis. Together, our results imply that inhibition of [[FGFR1]] endocytosis by MβCD or chlorpromazine promotes FGF-2-induced axonal branching. The results of this study confirm that internalization of [[FGFR1]] controls axon growth and morphology of adult sensory neurons via selective activation of intracellular signaling pathways.
|mesh-terms=* Aging
* Animals
* Apoptosis
* Axons
* Blotting, Western
* Chlorpromazine
* Dopamine Antagonists
* Endocytosis
* Ganglia, Spinal
* In Situ Nick-End Labeling
* Microscopy, Confocal
* Neurogenesis
* PC12 Cells
* Rats
* Receptor, Fibroblast Growth Factor, Type 1
* Sensory Receptor Cells
* Signal Transduction
* beta-Cyclodextrins

|full-text-url=https://sci-hub.do/10.1016/j.neuroscience.2011.04.064
}}
{{medline-entry
|title=FGF-2/[[FGFR1]] neurotrophic system expression level and its basal activation do not account for the age-dependent decline of precursor cell proliferation in the subventricular zone of rat brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20816673
|abstract=It is largely accepted that neurogenesis in the adult brain decreases with age and reduced levels of local neurotrophic support is speculated to be a contributing factor. Among neurotrophic factors involved on neurogenesis, we focused our attention on the neurotrophic system fibroblast growth factor-2 (FGF-2) and its receptor [[FGFR1]], a potent modulator of precursor cell proliferation. In the present work, we aimed to analyse if potential age-dependent changes of the FGF-2/[[FGFR1]] neurotrophic system may give account for the age-dependent decline of precursor cell proliferation in the neurogenic region of the subventricular zone (SVZ) in the rat brain. Using in situ hybridization and western blotting procedures we examined FGF-2 and [[FGFR1]] expression levels in the SVZ of 20-month-old rats as compared to young adult 3-month-old rats. The results showed that during aging the FGF-2 and its receptor expression levels, both as mRNA and protein, were unchanged in the SVZ. The levels of phosphorylated [[FGFR1]] form did not show significant variations suggesting that also the level of receptor activation does not change during aging. No changes were also observed in the phosphorylation of two [[FGFR1]] related proteins involved in intracellular signaling, the canonical extracellular signal-regulated kinase Erk1/2 and the phospholipase-Cγ1. Additionally, we could show that also the proliferation rate of stem cells does not change during aging. Taken together, our results show that FGF-2/[[FGFR1]] neurotrophic system expression level and its basal activation do not account for the age-dependent decline of precursor cell proliferation in the rat brain.
|mesh-terms=* Adult Stem Cells
* Aging
* Animals
* Brain
* Bromodeoxyuridine
* Cell Proliferation
* Cerebral Ventricles
* Fibroblast Growth Factor 1
* Fibroblast Growth Factor 2
* Gene Expression Regulation
* Male
* Mitogen-Activated Protein Kinase 3
* Neurogenesis
* Phospholipase C gamma
* Phosphorylation
* RNA, Messenger
* Rats
* Rats, Wistar
* Receptor, Fibroblast Growth Factor, Type 1

|full-text-url=https://sci-hub.do/10.1016/j.brainres.2010.08.083
}}
{{medline-entry
|title=Genetic variation in [[FGF20]] modulates hippocampal biology.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20427658
|abstract=We explored the effect of single-nucleotide polymorphisms (SNPs) in the fibroblast growth factor 20 gene ([[FGF20]]) associated with risk for Parkinson's disease on brain structure and function in a large sample of healthy young-adult human subjects and also in elderly subjects to look at the interaction between genetic variations and age (N = 237; 116 men; 18-87 years). We analyzed high-resolution anatomical magnetic resonance images using voxel-based morphometry, a quantitative neuroanatomical technique. We also measured [[FGF20]] mRNA expression in postmortem human brain tissue to determine the molecular correlates of these SNPs (N = 108; 72 men; 18-74 years). We found that the T allele carriers of rs12720208 in the 3'-untranslated region had relatively larger hippocampal volume (p = 0.0059) and diminished verbal episodic memory (p = 0.048) and showed steeper decreases of hippocampal volume with normal aging (p = 0.026). In postmortem brain, T allele carriers had greater expression of hippocampal [[FGF20]] mRNA (p = 0.037), consistent with a previously characterized microRNA mechanism. The C allele matches a predicted miR-433 microRNA binding domain, whereas the T allele disrupts it, resulting in higher [[FGF20]] protein translation. The strong [[FGF20]] genetic effects in hippocampus are presumably mediated by activation of the [[FGFR1]] (FGF receptor 1), which is expressed in mammalian brain most abundantly in the hippocampus. These associations, from mRNA expression to brain morphology to cognition and an interaction with aging, confirm a role of [[FGF20]] in human brain structure and function during development and aging.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Alleles
* Cognition
* Female
* Fibroblast Growth Factors
* Genotype
* Hippocampus
* Humans
* Male
* MicroRNAs
* Middle Aged
* Organ Size
* Polymorphism, Single Nucleotide
* RNA, Messenger
* Receptor, Fibroblast Growth Factor, Type 1
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909689
}}
{{medline-entry
|title=Nicotine-induced fibroblast growth factor-2 restores the age-related decline of precursor cell proliferation in the subventricular zone of rat brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18190895
|abstract=Precursor cell proliferation is present in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus of adult rat and persists during aging although at reduced levels. Previous studies have shown that acute intermittent nicotine treatment significantly increases fibroblast growth factor-2 (FGF-2) expression in several brain regions of aged rats. The aim of the present investigation was to test the hypothesis that nicotine-induced expression of FGF-2 may restore the age-related decline of precursor cell proliferation. It was first demonstrated that nicotine treatment increases both mRNA and protein FGF-2 in the SVZ of aged male rats (18 months old). The effect of nicotine on precursor cell proliferation in the SVZ was studied by i.p. injection of 5-bromo-2'-deoxyuridine (BrdU) 40 mg/kg to label dividing cells. The nicotine treatment was found to significantly enhance precursor cell proliferation in the SVZ. This increase was sufficiently large to restore the age-related decline of proliferating precursor cells observed in aged rats to that found in young adult rats (3 months old). FGF-2 was expressed in [[GFAP]]-positive cells and may act via its receptor [[FGFR1]] that was found expressed in nestin-positive cells of the SVZ. The data obtained demonstrated that the age-related decline of precursor cell proliferation may be counteracted by activating a trophic mechanism mediated by FGF-2.
|mesh-terms=* Adult Stem Cells
* Aging
* Analysis of Variance
* Animals
* Antibodies
* Brain
* Bromodeoxyuridine
* Cell Count
* Cell Proliferation
* Fibroblast Growth Factor 2
* Gene Expression Regulation
* Glial Fibrillary Acidic Protein
* Intermediate Filament Proteins
* Lateral Ventricles
* Male
* Nerve Tissue Proteins
* Nestin
* Nicotine
* Nicotinic Agonists
* Rats
* Rats, Wistar

|full-text-url=https://sci-hub.do/10.1016/j.brainres.2007.11.069
}}
{{medline-entry
|title=Expression of fibroblast growth factors and their receptors during full-thickness skin wound healing in young and aged mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16079254
|abstract=The highly ordered process of wound healing involves the coordinated regulation of cell proliferation and migration and tissue remodeling, predominantly by polypeptide growth factors. Consequently, the slowing of wound healing that occurs in the aged may be related to changes in the activity of these various regulatory factors. To gain additional insight into these issues, we quantified the absolute copy numbers of mRNAs encoding all the fibroblast growth factors (FGFs), their receptors (FGFRs) and two other growth factors in the dorsal skin of young and aged mice during the healing of full-thickness skin excisional wounds. In young adult mice (8 weeks old), [[FGF7]], [[FGF10]] and [[FGF22]] mRNAs were all strongly expressed in healthy skin, and levels of [[FGF7]] and 10 but not 22 increased 2- to 3.5-fold over differing time courses after wounding. The levels of [[FGF9]], 16, 18 and especially 23 mRNAs were moderate or low in healthy skin but increased 2- to 33-fold after wounding. Among the four FGFRs, expression of only [[FGFR1]] mRNA was augmented during wound healing. Expression of transforming growth factor-beta and hepatocyte growth factor was also high in healthy skin and was upregulated during healing. Notably, in aged mice (35 weeks old), where healing proceeded more slowly than in the young, both the basal and wound-induced mRNA expression of most of these genes was reduced. While these results confirm the established notion that [[FGFR2]] IIIB ligands ([[FGF7]] and [[FGF10]]) are important for wound healing, they also suggest that decreased expression of multiple FGF ligands contributes to the slowing of wound healing in aged mice and indicate the potential importance of further study of the involvement of [[FGF9]], 16, 18 and 23 in the wound healing process.
|mesh-terms=* Actins
* Aging
* Animals
* Fibroblast Growth Factors
* Gene Expression
* Glyceraldehyde-3-Phosphate Dehydrogenases
* Hepatocyte Growth Factor
* Male
* Mice
* Mice, Mutant Strains
* RNA, Messenger
* Receptors, Fibroblast Growth Factor
* Skin
* Transforming Growth Factor beta
* Wound Healing

|full-text-url=https://sci-hub.do/10.1677/joe.1.06055
}}
{{medline-entry
|title=Negative autoregulation of fibroblast growth factor receptor 2 expression characterizing cranial development in cases of Apert (P253R mutation) and Pfeiffer (C278F mutation) syndromes and suggesting a basis for differences in their cranial phenotypes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11596961
|abstract=Heterogeneous mutations in the fibroblast growth factor receptor 2 gene ([[FGFR2]]) cause a range of craniosynostosis syndromes. The specificity of the Apert syndrome-affected cranial phenotype reflects its narrow mutational range: 98% of cases of Apert syndrome result from an Ser252Trp or Pro253Arg mutation in the immunoglobulin-like (Ig)IIIa extracellular subdomain of [[FGFR2]]. In contrast, a broad range of mutations throughout the extracellular domain of [[FGFR2]] causes the overlapping cranial phenotypes of Pfeiffer and Crouzon syndromes and related craniofacial dysostoses. In this paper the expression of [[FGFR1]], the IgIIIa/c and IgIIIa/b isoforms of [[FGFR2]], and [[FGFR3]] is investigated in Apert syndrome (P253R mutation)- and Pfeiffer syndrome (C278F mutation)-affected fetal cranial tissue and is contrasted with healthy human control tissues. Both [[FGFR1]] and [[FGFR3]] are normally expressed in the differentiated osteoblasts of the periosteum and osteoid, in domains overlapped by that of [[FGFR2]], which widely include preosseous cranial mesenchyme. Expression of [[FGFR2]], however, is restricted to domains of advanced osseous differentiation in both Apert syndrome- and Pfeiffer syndrome-affected cranial skeletogenesis in the presence of fibroblast growth factor (FGF)2, but not in the presence of [[FGF4]] or [[FGF7]]. Whereas expression of the [[FGFR2]]-IgIIIa/b (KGFR) isoform is restricted in normal human cranial osteogenesis, there is preliminary evidence that KGFR is ectopically expressed in Pfeiffer syndrome-affected cranial osteogenesis. Contraction of the [[FGFR2]]-IgIIIa/c (BEK) expression domain in cases of Apert syndrome- and Pfeiffer syndrome-affected fetal cranial ossification suggests that the mutant activation of this receptor, by ligand-dependent or ligand-independent means, results in negative autoregulation. This phenomenon, resulting from different mechanisms in the two syndromes, offers a model by which to explain differences in their cranial phenotypes.
|mesh-terms=* Acrocephalosyndactylia
* Aging
* Embryonic and Fetal Development
* Fetus
* Homeostasis
* Humans
* Infant
* Mutation
* Osteogenesis
* Phenotype
* Receptor Protein-Tyrosine Kinases
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Receptors, Fibroblast Growth Factor
* Skull

|full-text-url=https://sci-hub.do/10.3171/jns.2001.95.4.0660
}}
{{medline-entry
|title=Attenuation of FGF signalling in mouse beta-cells leads to diabetes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11130726
|abstract=Fibroblast growth factor (FGF) signalling has been implicated in patterning, proliferation and cell differentiation in many organs, including the developing pancreas. Here we show that the FGF receptors (FGFRs) 1 and 2, together with the ligands [[FGF1]], [[FGF2]], [[FGF4]], [[FGF5]], [[FGF7]] and [[[[FGF1]]0]], are expressed in adult mouse beta-cells, indicating that FGF signalling may have a role in differentiated beta-cells. When we perturbed signalling by expressing dominant-negative forms of the receptors, [[FGFR1]]c and FGFR2b, in the pancreas, we found that that mice with attenuated [[FGFR1]]c signalling, but not those with reduced FGFR2b signalling, develop diabetes with age and exhibit a decreased number of beta-cells, impaired expression of glucose transporter 2 and increased proinsulin content in beta-cells owing to impaired expression of prohormone convertases 1/3 and 2. These defects are all characteristic of patients with type-2 diabetes. Mutations in the homeobox gene Ipf1/Pdx1 are linked to diabetes in both mouse and human. We also show that Ipf1/Pdx1 is required for the expression of [[FGFR1]] signalling components in beta-cells, indicating that Ipf1/Pdx1 acts upstream of [[FGFR1]] signalling in beta-cells to maintain proper glucose sensing, insulin processing and glucose homeostasis.
|mesh-terms=* Aging
* Animals
* Blood Glucose
* Diabetes Mellitus, Experimental
* Diabetes Mellitus, Type 2
* Fibroblast Growth Factors
* Glucose Transporter Type 1
* Glucose Transporter Type 2
* Homeodomain Proteins
* Humans
* Insulin
* Islets of Langerhans
* Mice
* Mice, Transgenic
* Monosaccharide Transport Proteins
* Pancreas
* Receptor Protein-Tyrosine Kinases
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Receptors, Fibroblast Growth Factor
* Signal Transduction
* Trans-Activators

|full-text-url=https://sci-hub.do/10.1038/35048589
}}
{{medline-entry
|title=Basic fibroblast growth factor (bFGF) and two of its receptors, [[FGFR1]] and [[FGFR2]]: gene expression in the rat brain during postnatal development as determined by quantitative RT-PCR.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/7527353
|abstract=Regional and temporal patterns of the expression of basic fibroblast growth factor (bFGF), and two of its high affinity receptors ([[FGFR1]] and [[FGFR2]]), were examined in the male rat brain during early postnatal development; the reverse transcription-polymerase chain reaction (RT-PCR) was used to obtain mRNA measurements which were expressed relative to mRNA for [[GAPDH]] as a constant. In the rat cerebrum, the mRNAs for bFGF and for [[FGFR2]] were relatively low in amount within the first postnatal week, but by 28 days, they were as high as in the 1-year-old rat cerebrum. In contrast, the expression of [[FGFR1]] was biphasic: mRNA levels were higher at postnatal days 1 and 28 than at day 21. Quantitation of mRNA from microdissected regions of 28-day-old rat brain revealed that the expression of bFGF and of [[FGFR2]] showed a marked variation between regions but the expression of [[FGFR1]] appeared less variable between the regions that were analyzed. For all three genes the hippocampus appeared to have high relative amounts of mRNA. The temporal patterns of expression of bFGF, [[FGFR1]] and [[FGFR2]] also differed with brain region during early postnatal development. In the occipital cortex and inferior colliculus, the mRNAs for bFGF and [[FGFR2]] both increased in amount during the first month, unlike that for [[FGFR1]]. However, in the cerebellum, the highest expression of bFGF and [[FGFR1]] mRNAs occurred at postnatal day 1; [[FGFR2]] expression apparently showed less change with age. The temporal changes in bFGF, [[FGFR1]] and [[FGFR2]] expression in different brain regions during early postnatal development suggest that receptor regulation may permit different physiological effects of bFGF according to brain region and developmental age.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Base Sequence
* Brain
* Cerebellum
* Fibroblast Growth Factor 2
* Gene Expression
* Hippocampus
* Inferior Colliculi
* Male
* Meninges
* Molecular Sequence Data
* Occipital Lobe
* Polymerase Chain Reaction
* RNA, Messenger
* RNA-Directed DNA Polymerase
* Rats
* Rats, Sprague-Dawley
* Receptors, Fibroblast Growth Factor
* Tissue Distribution

|full-text-url=https://sci-hub.do/10.1016/0303-7207(94)90122-8
}}

FGFBP1

2021-05-12T15:37:02Z

OdysseusBot: Новая страница: «Fibroblast growth factor-binding protein 1 precursor (FGF-BP) (FGF-BP1) (FGF-binding protein 1) (FGFBP-1) (17 kDa heparin-binding growth factor-binding protein) (...»

Fibroblast growth factor-binding protein 1 precursor (FGF-BP) (FGF-BP1) (FGF-binding protein 1) (FGFBP-1) (17 kDa heparin-binding growth factor-binding protein) (17 kDa HBGF-binding protein) (HBp17) [FGFBP] [HBP17]

==Publications==

{{medline-entry
|title=Muscle Fibers Secrete [[FGFBP1]] to Slow Degeneration of Neuromuscular Synapses during Aging and Progression of ALS.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28053031
|abstract=The identity of muscle secreted factors critical for the development and maintenance of neuromuscular junctions (NMJs) remains largely unknown. Here, we show that muscle fibers secrete and concentrate the fibroblast growth factor binding protein 1 ([[FGFBP1]]) at NMJs. Although [[FGFBP1]] expression increases during development, its expression decreases before NMJ degeneration during aging and in [[SOD1]] mice, a mouse model for amyotrophic lateral sclerosis (ALS). Based on these findings, we examined the impact of deleting [[FGFBP1]] on NMJs. In the absence of [[FGFBP1]], NMJs exhibit structural abnormalities in developing and middle age mice. Deletion of [[FGFBP1]] from [[SOD1]] mice also accelerates NMJ degeneration and death. Based on these findings, we sought to identify the mechanism responsible for decreased [[FGFBP1]] in stressed skeletal muscles. We show that [[FGFBP1]] expression is inhibited by increased accumulation of the transforming growth factor-β1 (TGF-β1) in skeletal muscles and at their NMJs. These findings suggest that targeting the [[FGFBP1]] and TGF-β1 signaling axis holds promise for slowing age- and disease-related degeneration of NMJs. The neuromuscular junction (NMJ) is critical for all voluntary movement. Its malformation during development and degeneration in adulthood impairs motor function. Therefore, it is important to identify factors that function to maintain the structural integrity of NMJs. We show that muscle fibers secrete and concentrate the fibroblast growth factor binding protein 1 ([[FGFBP1]]) at NMJs. However, [[FGFBP1]] expression decreases in skeletal muscles during aging and before NMJ degeneration in [[SOD1]] mice, a mouse model for amyotrophic lateral sclerosis. We show that transforming growth factor-β1 is responsible for the decreased levels of [[FGFBP1]]. Importantly, we demonstrate critical roles for [[FGFBP1]] at NMJs in developing, aging and [[SOD1]] mice.
|mesh-terms=* Aging
* Amyotrophic Lateral Sclerosis
* Animals
* Axons
* Carrier Proteins
* Intercellular Signaling Peptides and Proteins
* Intracellular Signaling Peptides and Proteins
* Mice
* Mice, Knockout
* Muscle Fibers, Skeletal
* Muscle, Skeletal
* Nerve Degeneration
* Nerve Regeneration
* Neuromuscular Junction
* Superoxide Dismutase-1
* Synapses
* Transforming Growth Factor beta1
|keywords=* Lou Gehrig's disease
* axonal regeneration
* cytokine
* geriatric
* synaptic elimination
* target-derived
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214636
}}

FGF8

2021-05-12T15:36:58Z

OdysseusBot: Новая страница: «Fibroblast growth factor 8 precursor (FGF-8) (Androgen-induced growth factor) (AIGF) (Heparin-binding growth factor 8) (HBGF-8) [AIGF] ==Publications== {{medlin...»

Fibroblast growth factor 8 precursor (FGF-8) (Androgen-induced growth factor) (AIGF) (Heparin-binding growth factor 8) (HBGF-8) [AIGF]

==Publications==

{{medline-entry
|title=Prostatic microenvironment in senescence: fibroblastic growth factors × hormonal imbalance.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24362909
|abstract=The aim was to characterize and correlate steroid hormone receptors with the [[FGF2]], [[FGF7]] and [[FGF8]] reactivities in the prostatic epithelium and stroma in senile rats. Fifty male senile rats and 10 young male rats were divided into the young (YNG), the senile groups (SE), the castrated group (CAS), the estrogen-deficient group (ED), the castrated estrogen group (CASE), and the estrogen-deficient androgen group (EDTEST). The ventral prostate was submitted to immunohistochemical and Western blotting analyses. The results showed decreased [[AR]] and ERβ levels and increased ERα in the senile animals in relation to YNG group. Increased ERα and ERβ reactivities presenting differential localization were characterized in the CASE group compared to the CAS group. Increased [[FGF2]] level was observed in the stroma of the CAS and ED groups in relation to the SE group and in the epithelium of the ED group in relation to the other groups. Increased and differential immunolocalization of [[FGF7]] levels were observed in the CAS, ED and CASE groups. The [[FGF8]] levels showed differential localization in the CAS and ED groups compared to the senile group. The intense hormone ablation was favorable to the autocrine signaling of [[FGF2]] and [[FGF8]]. [[FGF7]] could be activated in the androgen-independent via considering the increased [[FGF7]] in the castrated rats. We concluded that hormone ablation in senescence was favorable to activation or/and to fibroblast signaling in the prostatic microenvironment.
|mesh-terms=* Aging
* Animals
* Cellular Microenvironment
* Estrogens
* Fibroblast Growth Factors
* Gonadal Steroid Hormones
* Male
* Orchiectomy
* Prostate
* Rats
* Rats, Sprague-Dawley
* Receptors, Androgen
* Receptors, Estrogen
* Testosterone

|full-text-url=https://sci-hub.do/10.1007/s00418-013-1173-y
}}
{{medline-entry
|title=HSPG-deficient zebrafish uncovers dental aspect of multiple osteochondromas.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22253766
|abstract=Multiple Osteochondromas (MO; previously known as multiple hereditary exostosis) is an autosomal dominant genetic condition that is characterized by the formation of cartilaginous bone tumours (osteochondromas) at multiple sites in the skeleton, secondary bursa formation and impingement of nerves, tendons and vessels, bone curving, and short stature. MO is also known to be associated with arthritis, general pain, scarring and occasional malignant transformation of osteochondroma into secondary peripheral chondrosarcoma. MO patients present additional complains but the relevance of those in relation to the syndromal background needs validation. Mutations in two enzymes that are required during heparan sulphate synthesis (EXT1 or EXT2) are known to cause MO. Previously, we have used zebrafish which harbour mutations in ext2 as a model for MO and shown that ext2⁻/⁻ fish have skeletal defects that resemble those seen in osteochondromas. Here we analyse dental defects present in ext2⁻/⁻ fish. Histological analysis reveals that ext2⁻/⁻ fish have very severe defects associated with the formation and the morphology of teeth. At 5 days post fertilization 100% of ext2⁻/⁻ fish have a single tooth at the end of the 5(th) pharyngeal arch, whereas wild-type fish develop three teeth, located in the middle of the pharyngeal arch. ext2⁻/⁻ teeth have abnormal morphology (they were shorter and thicker than in the WT) and patchy ossification at the tooth base. Deformities such as split crowns and enamel lesions were found in 20% of ext2⁺/⁻ adults. The tooth morphology in ext2⁻/⁻ was partially rescued by [[FGF8]] administered locally (bead implants). Our findings from zebrafish model were validated in a dental survey that was conducted with assistance of the MHE Research Foundation. The presence of the malformed and/or displaced teeth with abnormal enamel was declared by half of the respondents indicating that MO might indeed be also associated with dental problems.
|mesh-terms=* Adult
* Aging
* Animals
* Biomarkers
* Exostoses, Multiple Hereditary
* Gene Expression Regulation, Developmental
* Heparan Sulfate Proteoglycans
* Humans
* Larva
* Mutation
* N-Acetylglucosaminyltransferases
* Phenotype
* Signal Transduction
* Tooth
* Tooth Diseases
* Zebrafish

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256178
}}

FGF7

2021-05-12T15:36:55Z

OdysseusBot: Новая страница: «Fibroblast growth factor 7 precursor (FGF-7) (Heparin-binding growth factor 7) (HBGF-7) (Keratinocyte growth factor) [KGF] ==Publications== {{medline-entry |tit...»

Fibroblast growth factor 7 precursor (FGF-7) (Heparin-binding growth factor 7) (HBGF-7) (Keratinocyte growth factor) [KGF]

==Publications==

{{medline-entry
|title=Prostatic microenvironment in senescence: fibroblastic growth factors × hormonal imbalance.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24362909
|abstract=The aim was to characterize and correlate steroid hormone receptors with the [[FGF2]], [[FGF7]] and [[FGF8]] reactivities in the prostatic epithelium and stroma in senile rats. Fifty male senile rats and 10 young male rats were divided into the young (YNG), the senile groups (SE), the castrated group (CAS), the estrogen-deficient group (ED), the castrated estrogen group (CASE), and the estrogen-deficient androgen group (EDTEST). The ventral prostate was submitted to immunohistochemical and Western blotting analyses. The results showed decreased [[AR]] and ERβ levels and increased ERα in the senile animals in relation to YNG group. Increased ERα and ERβ reactivities presenting differential localization were characterized in the CASE group compared to the CAS group. Increased [[FGF2]] level was observed in the stroma of the CAS and ED groups in relation to the SE group and in the epithelium of the ED group in relation to the other groups. Increased and differential immunolocalization of [[FGF7]] levels were observed in the CAS, ED and CASE groups. The [[FGF8]] levels showed differential localization in the CAS and ED groups compared to the senile group. The intense hormone ablation was favorable to the autocrine signaling of [[FGF2]] and [[FGF8]]. [[FGF7]] could be activated in the androgen-independent via considering the increased [[FGF7]] in the castrated rats. We concluded that hormone ablation in senescence was favorable to activation or/and to fibroblast signaling in the prostatic microenvironment.
|mesh-terms=* Aging
* Animals
* Cellular Microenvironment
* Estrogens
* Fibroblast Growth Factors
* Gonadal Steroid Hormones
* Male
* Orchiectomy
* Prostate
* Rats
* Rats, Sprague-Dawley
* Receptors, Androgen
* Receptors, Estrogen
* Testosterone

|full-text-url=https://sci-hub.do/10.1007/s00418-013-1173-y
}}
{{medline-entry
|title=Expression of fibroblast growth factors and their receptors during full-thickness skin wound healing in young and aged mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16079254
|abstract=The highly ordered process of wound healing involves the coordinated regulation of cell proliferation and migration and tissue remodeling, predominantly by polypeptide growth factors. Consequently, the slowing of wound healing that occurs in the aged may be related to changes in the activity of these various regulatory factors. To gain additional insight into these issues, we quantified the absolute copy numbers of mRNAs encoding all the fibroblast growth factors (FGFs), their receptors (FGFRs) and two other growth factors in the dorsal skin of young and aged mice during the healing of full-thickness skin excisional wounds. In young adult mice (8 weeks old), [[FGF7]], [[FGF10]] and [[FGF22]] mRNAs were all strongly expressed in healthy skin, and levels of [[FGF7]] and 10 but not 22 increased 2- to 3.5-fold over differing time courses after wounding. The levels of [[FGF9]], 16, 18 and especially 23 mRNAs were moderate or low in healthy skin but increased 2- to 33-fold after wounding. Among the four FGFRs, expression of only [[FGFR1]] mRNA was augmented during wound healing. Expression of transforming growth factor-beta and hepatocyte growth factor was also high in healthy skin and was upregulated during healing. Notably, in aged mice (35 weeks old), where healing proceeded more slowly than in the young, both the basal and wound-induced mRNA expression of most of these genes was reduced. While these results confirm the established notion that [[FGFR2]] IIIB ligands ([[FGF7]] and [[FGF10]]) are important for wound healing, they also suggest that decreased expression of multiple FGF ligands contributes to the slowing of wound healing in aged mice and indicate the potential importance of further study of the involvement of [[FGF9]], 16, 18 and 23 in the wound healing process.
|mesh-terms=* Actins
* Aging
* Animals
* Fibroblast Growth Factors
* Gene Expression
* Glyceraldehyde-3-Phosphate Dehydrogenases
* Hepatocyte Growth Factor
* Male
* Mice
* Mice, Mutant Strains
* RNA, Messenger
* Receptors, Fibroblast Growth Factor
* Skin
* Transforming Growth Factor beta
* Wound Healing

|full-text-url=https://sci-hub.do/10.1677/joe.1.06055
}}
{{medline-entry
|title=Negative autoregulation of fibroblast growth factor receptor 2 expression characterizing cranial development in cases of Apert (P253R mutation) and Pfeiffer (C278F mutation) syndromes and suggesting a basis for differences in their cranial phenotypes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11596961
|abstract=Heterogeneous mutations in the fibroblast growth factor receptor 2 gene ([[FGFR2]]) cause a range of craniosynostosis syndromes. The specificity of the Apert syndrome-affected cranial phenotype reflects its narrow mutational range: 98% of cases of Apert syndrome result from an Ser252Trp or Pro253Arg mutation in the immunoglobulin-like (Ig)IIIa extracellular subdomain of [[FGFR2]]. In contrast, a broad range of mutations throughout the extracellular domain of [[FGFR2]] causes the overlapping cranial phenotypes of Pfeiffer and Crouzon syndromes and related craniofacial dysostoses. In this paper the expression of [[FGFR1]], the IgIIIa/c and IgIIIa/b isoforms of [[FGFR2]], and [[FGFR3]] is investigated in Apert syndrome (P253R mutation)- and Pfeiffer syndrome (C278F mutation)-affected fetal cranial tissue and is contrasted with healthy human control tissues. Both [[FGFR1]] and [[FGFR3]] are normally expressed in the differentiated osteoblasts of the periosteum and osteoid, in domains overlapped by that of [[FGFR2]], which widely include preosseous cranial mesenchyme. Expression of [[FGFR2]], however, is restricted to domains of advanced osseous differentiation in both Apert syndrome- and Pfeiffer syndrome-affected cranial skeletogenesis in the presence of fibroblast growth factor (FGF)2, but not in the presence of [[FGF4]] or [[FGF7]]. Whereas expression of the [[FGFR2]]-IgIIIa/b (KGFR) isoform is restricted in normal human cranial osteogenesis, there is preliminary evidence that KGFR is ectopically expressed in Pfeiffer syndrome-affected cranial osteogenesis. Contraction of the [[FGFR2]]-IgIIIa/c (BEK) expression domain in cases of Apert syndrome- and Pfeiffer syndrome-affected fetal cranial ossification suggests that the mutant activation of this receptor, by ligand-dependent or ligand-independent means, results in negative autoregulation. This phenomenon, resulting from different mechanisms in the two syndromes, offers a model by which to explain differences in their cranial phenotypes.
|mesh-terms=* Acrocephalosyndactylia
* Aging
* Embryonic and Fetal Development
* Fetus
* Homeostasis
* Humans
* Infant
* Mutation
* Osteogenesis
* Phenotype
* Receptor Protein-Tyrosine Kinases
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Receptors, Fibroblast Growth Factor
* Skull

|full-text-url=https://sci-hub.do/10.3171/jns.2001.95.4.0660
}}
{{medline-entry
|title=Attenuation of FGF signalling in mouse beta-cells leads to diabetes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11130726
|abstract=Fibroblast growth factor (FGF) signalling has been implicated in patterning, proliferation and cell differentiation in many organs, including the developing pancreas. Here we show that the FGF receptors (FGFRs) 1 and 2, together with the ligands [[FGF1]], [[FGF2]], [[FGF4]], [[FGF5]], [[FGF7]] and [[[[FGF1]]0]], are expressed in adult mouse beta-cells, indicating that FGF signalling may have a role in differentiated beta-cells. When we perturbed signalling by expressing dominant-negative forms of the receptors, [[FGFR1]]c and FGFR2b, in the pancreas, we found that that mice with attenuated [[FGFR1]]c signalling, but not those with reduced FGFR2b signalling, develop diabetes with age and exhibit a decreased number of beta-cells, impaired expression of glucose transporter 2 and increased proinsulin content in beta-cells owing to impaired expression of prohormone convertases 1/3 and 2. These defects are all characteristic of patients with type-2 diabetes. Mutations in the homeobox gene Ipf1/Pdx1 are linked to diabetes in both mouse and human. We also show that Ipf1/Pdx1 is required for the expression of [[FGFR1]] signalling components in beta-cells, indicating that Ipf1/Pdx1 acts upstream of [[FGFR1]] signalling in beta-cells to maintain proper glucose sensing, insulin processing and glucose homeostasis.
|mesh-terms=* Aging
* Animals
* Blood Glucose
* Diabetes Mellitus, Experimental
* Diabetes Mellitus, Type 2
* Fibroblast Growth Factors
* Glucose Transporter Type 1
* Glucose Transporter Type 2
* Homeodomain Proteins
* Humans
* Insulin
* Islets of Langerhans
* Mice
* Mice, Transgenic
* Monosaccharide Transport Proteins
* Pancreas
* Receptor Protein-Tyrosine Kinases
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Receptors, Fibroblast Growth Factor
* Signal Transduction
* Trans-Activators

|full-text-url=https://sci-hub.do/10.1038/35048589
}}

FGF6

2021-05-12T15:36:53Z

OdysseusBot: Новая страница: «Fibroblast growth factor 6 precursor (FGF-6) (Heparin secretory-transforming protein 2) (HST-2) (HSTF-2) (Heparin-binding growth factor 6) (HBGF-6) [HST2] [HSTF2]...»

Fibroblast growth factor 6 precursor (FGF-6) (Heparin secretory-transforming protein 2) (HST-2) (HSTF-2) (Heparin-binding growth factor 6) (HBGF-6) [HST2] [HSTF2]

==Publications==

{{medline-entry
|title=Genome-wide associations and detection of potential candidate genes for direct genetic and maternal genetic effects influencing dairy cattle body weight at different ages.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30727969
|abstract=Body weight (BW) at different ages are of increasing importance in dairy cattle breeding schemes, because of their strong correlation with energy efficiency traits, and their impact on cow health, longevity and farm economy. In total, 15,921 dairy cattle from 56 large-scale test-herds with BW records were genotyped for 45,613 single nucleotide polymorphisms (SNPs). This dataset was used for genome-wide association studies (GWAS), in order to localize potential candidate genes for direct and maternal genetic effects on BW recorded at birth (BW0), at 2 to 3 months of age (BW23), and at 13 to 14 months of age (BW1314). The first 20 principal components ([[PC]]) of the genomic relationship matrix ([Formula: see text]) grouped the genotyped cattle into three clusters. In the statistical models used for GWAS, correction for population structure was done by including polygenic effects with various genetic similarity matrices, such as the pedigree-based relationship matrix ([Formula: see text]), the [Formula: see text]-matrix, the reduced [Formula: see text]-matrix LOCO (i.e. exclusion of the chromosome on which the candidate SNP is located), and LOCO plus chromosome-wide [[PC]]. Inflation factors for direct genetic effects using [Formula: see text] and LOCO were larger than 1.17. For [Formula: see text] and LOCO plus chromosome-wide [[PC]], inflation factors were very close to 1.0. According to Bonferroni correction, ten, two and seven significant SNPs were detected for the direct genetic effect on BW0, BW23, and BW1314, respectively. Seventy-six candidate genes contributed to direct genetic effects on BW with four involved in growth and developmental processes: [[FGF6]], [[FGF23]], [[TNNT3]], and [[OMD]]. For maternal genetic effects on BW0, only three significant SNPs (according to Bonferroni correction), and four potential candidate genes, were identified. The most significant SNP on chromosome 19 explained only 0.14% of the maternal de-regressed proof variance for BW0. For correction of population structure in GWAS, we suggest a statistical model that considers LOCO plus chromosome-wide [[PC]]. Regarding direct genetic effects, several SNPs had a significant effect on BW at different ages, and only two SNPs on chromosome 5 had a significant effect on all three BW traits. Thus, different potential candidate genes regulate BW at different ages. Maternal genetic effects followed an infinitesimal model.
|mesh-terms=* Aging
* Animals
* Body Weight
* Cattle
* Extracellular Matrix Proteins
* Female
* Fibroblast Growth Factors
* Genome-Wide Association Study
* Male
* Polymorphism, Single Nucleotide
* Proteoglycans
* Quantitative Trait Loci
* Troponin T

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366057
}}
{{medline-entry
|title=Regulation of skeletal muscle stem cells by fibroblast growth factors.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28249356
|abstract=Fibroblast growth factors (FGFs) are essential for self-renewal of skeletal muscle stem cells (satellite cells) and required for maintenance and repair of skeletal muscle. Satellite cells express high levels of FGF receptors 1 and 4, low levels of FGF receptor 3, and little or no detectable FGF receptor 2. Of the multiple FGFs that influence satellite cell function in culture, [[FGF2]] and [[FGF6]] are the only members that regulate satellite cell function in vivo by activating ERK MAPK, p38α/β MAPKs, [[PI3]] kinase, PLCγ and STATs. Regulation of FGF signaling is complex in satellite cells, requiring Syndecan-4, a heparan sulfate proteoglycan, as well as ß1-integrin and fibronectin. During aging, reduced responsiveness to FGF diminishes satellite cell self-renewal, leading to impaired skeletal muscle regeneration and depletion of satellite cells. Mislocalization of ß1-integrin, reductions in fibronectin, and alterations in heparan sulfate content all contribute to reduced FGF responsiveness in satellite cells. How these cell surface proteins regulate satellite cell self-renewal is incompletely understood. Here we summarize the current knowledge, highlighting the role(s) for FGF signaling in skeletal muscle regeneration, satellite cell behavior, and age-induced muscle wasting. Developmental Dynamics 246:359-367, 2017. © 2017 Wiley Periodicals, Inc.
|mesh-terms=* Aging
* Animals
* Cell Self Renewal
* Fibroblast Growth Factors
* Humans
* Muscle, Skeletal
* Satellite Cells, Skeletal Muscle
* Signal Transduction
* Stem Cells
|keywords=* FGF
* regeneration
* satellite cell
* skeletal muscle
* stem cell
|full-text-url=https://sci-hub.do/10.1002/dvdy.24495
}}

FGF23

2021-05-12T15:36:49Z

OdysseusBot: Новая страница: «Fibroblast growth factor 23 precursor (FGF-23) (Phosphatonin) (Tumor-derived hypophosphatemia-inducing factor) [Contains: Fibroblast growth factor 23 N-terminal p...»

Fibroblast growth factor 23 precursor (FGF-23) (Phosphatonin) (Tumor-derived hypophosphatemia-inducing factor) [Contains: Fibroblast growth factor 23 N-terminal peptide; Fibroblast growth factor 23 C-terminal peptide] [HYPF] [UNQ3027/PRO9828]

==Publications==

{{medline-entry
|title=Phosphate as a Pathogen of Arteriosclerosis and Aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33028781
|abstract=During the evolution of skeletons, terrestrial vertebrates acquired strong bones made of calcium-phosphate. By keeping the extracellular fluid in a supersaturated condition regarding calcium and phosphate ions, they created the bone when and where they wanted simply by providing a cue for precipitation. To secure this strategy, they acquired a novel endocrine system to strictly control the extracellular phosphate concentration. In response to phosphate intake, fibroblast growth factor-23 ([[FGF23]]) is secreted from the bone and acts on the kidney through binding to its receptor Klotho to increase urinary phosphate excretion, thereby maintaining phosphate homeostasis. The [[FGF23]]-Klotho endocrine system, when disrupted in mice, results in hyperphosphatemia and vascular calcification. Besides, mice lacking Klotho or [[FGF23]] suffer from complex aging-like phenotypes, which are alleviated by placing them on a low-phosphate diet, indicating that phosphate is primarily responsible for the accelerated aging. Phosphate acquires the ability to induce cell damage and inflammation when precipitated with calcium. In the blood, calcium-phosphate crystals are adsorbed by serum protein fetuin-A and prevented from growing into large precipitates. Consequently, nanoparticles that comprised calcium-phosphate crystals and fetuin-A, termed calciprotein particles (CPPs), are generated and dispersed as colloids. CPPs increase in the blood with an increase in serum phosphate and age. Circulating CPP levels correlate positively with vascular stiffness and chronic non-infectious inflammation, raising the possibility that CPPs may be an endogenous pro-aging factor. Terrestrial vertebrates with the bone made of calcium-phosphate may be destined to age due to calcium-phosphate in the blood.

|keywords=* Aging
* Calciprotein particles (CPPs)
* Fibroblast growth factor-23 (FGF23)
* Inflammation
* Klotho
* Phosphate
* Vascular calcification
|full-text-url=https://sci-hub.do/10.5551/jat.RV17045
}}
{{medline-entry
|title=Plasma Soluble αKlotho, Serum Fibroblast Growth Factor 23, and Mobility Disability in Community-Dwelling Older Adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32405607
|abstract=αKlotho is a hormone and co-receptor for fibroblast growth factor 23 ([[FGF23]]), a hormone that downregulates active vitamin D synthesis and promotes phosphate excretion. Low αKlotho and high [[FGF23]] occur in chronic kidney disease (CKD). We aimed to assess the relationships of αKlotho and [[FGF23]] with mobility disability in community-dwelling older adults. We estimated associations of plasma-soluble αKlotho and serum [[FGF23]] concentrations with mobility disability over 6 years. Additional analyses was stratified by CKD. Participants included 2751 adults (25.0% with CKD), aged 71 to 80 years, from the 1998 to 1999 Health, Aging, and Body Composition Study visit. Walking disability and stair climb disability were defined as self-reported "a lot of difficulty" or an inability to walk a quarter mile and climb 10 stairs, respectively. Median (interquartile range [IQR]) serum [[FGF23]] and plasma soluble αKlotho concentrations were 46.6 (36.7, 60.2) pg/mL and 630.4 (478.4, 816.0) pg/mL, respectively. After adjustment, higher αKlotho concentrations were associated with lower walking disability rates (Rate Ratio [RR] highest vs. lowest tertile = 0.74; 95% confidence interval l [CI] = 0.62, 0.89; [i]P[/i] = 0.003). Higher [[FGF23]] concentrations were associated with higher walking disability rates (RR highest vs. lowest tertile = 1.24; 95%CI = 1.03, 1.50; [i]P[/i] = 0.005). Overall, higher αKlotho combined with lower [[FGF23]] was associated with the lowest walking disability rates ([i]P[/i] for interaction = 0.023). Stair climb disability findings were inconsistent. No interactions with CKD were statistically significant ([i]P[/i] for interaction > 0.10). Higher plasma soluble αKlotho and lower serum [[FGF23]] concentrations were associated with lower walking disability rates in community-dwelling older adults, particularly those without CKD.

|keywords=* aging
* chronic kidney disease
* fibroblast growth factor 23
* mobility disability
* αKlotho
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209777
}}
{{medline-entry
|title=Astragalus improve aging bone marrow mesenchymal stem cells (BMSCs) vitality and osteogenesis through VD-[[FGF23]]-Klotho axis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32355520
|abstract=To clarify the regulation of astragalus on the aging BMSCs model and the effect of astragalus on Vitamin D (VD)-[[FGF23]]-Klotho axis. siRNA was used to interfere the expression of [[VDR]] gene in aging BMSCs. Serum containing astragalus in different concentrations was added to the cultured cells. The expression of osteocalcin and alkaline phosphatase were detected by alizarin red staining and ELISA. Cell vitality was detected by flow cytometry, [[CCK]]-8 test, and [i]β[/i]-galactosidase staining. The expression of [[FGF23]], Klotho, [[CYP27B1]], and [[CYP24A1]] was detected by qRT-PCR and western blot. The results showed that after reducing [[VDR]] gene expression, the aging BMSCs model showed decreased activity and osteogenic ability, increased expression of [[FGF23]], Klotho and [[CYP24A1]], and decreased expression of [[CYP27B1]]. After adding serum-containing astragalus, the activity of cells and the osteogenic ability was increased; the expression levels of [[FGF23]], Klotho and [[CYP24A1]] were decreased, the expression levels of [[CYP27B1]] were increased, and the trend was more obvious with the increase of astragalus concentration. This study confirmed that astragalus could inhibit the aging of BMSCs and improve the osteogenesis ability by regulating the VD-[[FGF23]]-Klotho pathway. This study provided a certain research basis for the therapeutic of traditional Chinese medicine (TCM) on primary osteoporosis.

|keywords=* Astragalus
* BMSCs
* VD-FGF23-Klotho axis
* aging
* osteogenesis differentiation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191145
}}
{{medline-entry
|title=Protective effect of Polygonatum sibiricum Polysaccharide on D-galactose-induced aging rats model.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32042011
|abstract=The polysaccharide of Polygonatum sibiricum (PSP)is one of the main active ingredients of Polygonatum Polygonatum in Liliaceae. It has anti-tumor, anti-aging, immune regulation, and anti-oxidative effects. Recent studies have shown that the Klotho gene and fibroblast growth factor-23 (FGF-23) have a common receptor, which is closely related to aging and highly expressed in kidney and meninges. Our study aimed to investigate the anti-aging effect of PSP on D-galactose-induced rats and its mechanism. D-galactose (120 mg Kg ) and PSP (100 mg Kg ) was used to intervene in rats, respectively. Then The changes of indexes of the natural aging-like model rats before and after PSP intervention were observed. We found that PSP could significantly improve the learning and memory abilities of rats and reverse the pathological changes of kidney tissues in rats. At the same time, PSP up-regulated the expression of Klotho mRNA and Klotho protein in the renal cortex, down-regulated the expression of FOXO3a mRNA and p-FOXO3a protein in renal tissue, and inhibited the expression of FGF-23 protein in the femur. Our studies suggest that PSP may play a role by regulating the Klotho-[[FGF23]] endocrine axis, alleviating oxidative stress, and balancing calcium and phosphorus metabolism.
|mesh-terms=* Aging
* Animals
* Calcium
* Dietary Carbohydrates
* Fibroblast Growth Factors
* Galactose
* Glucuronidase
* Male
* Oxidative Stress
* Phosphorus
* Phytochemicals
* Polygonatum
* Polysaccharides
* Protective Agents
* Rats
* Rats, Sprague-Dawley

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010663
}}
{{medline-entry
|title=[[FGF23]] expression is stimulated in transgenic α-Klotho longevity mouse model.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31801907
|abstract=Observations in transgenic α-Klotho (Kl) mice (KlTg) defined the antiaging role of soluble Klotho (s[[KL]]130). A genetic translocation that elevates s[[KL]] levels in humans is paradoxically associated with increased circulating fibroblast growth factor 23 ([[FGF23]]) levels and the potential of both membrane [[KL]] (m[[KL]]135) and s[[KL]]130 to act as coreceptors for [[FGF23]] activation of fibroblast growth factor receptors (FGFRs). Neither [[FGF23]] expression nor the contributions of [[FGF23]], m[[KL]]135, and s[[KL]]130 codependent and independent functions have been investigated in KlTg mice. In the current study, we examined the effects of Kl overexpression on [[FGF23]] levels and functions in KlTg mice. We found that m[[KL]]135 but not s[[KL]]130 stimulated [[FGF23]] expression in osteoblasts, leading to elevated Fgf23 bone expression and circulating levels in KlTg mice. Elevated [[FGF23]] suppressed 1,25(OH)2D and parathyroid hormone levels but did not cause hypophosphatemic rickets in KlTg mice. KlTg mice developed low aldosterone-associated hypertension but not left ventricular hypertrophy. Mechanistically, we found that m[[KL]]135 and s[[KL]]130 are essential cofactors for [[FGF23]]-mediated ERK activation but that they inhibited [[FGF23]] stimulation of PLC-γ and PI3K/AKT signaling. Thus, increased longevity in KlTg mice occurs in the presence of excess [[FGF23]] that interacts with m[[KL]] and s[[KL]] to bias FGFR pathways.
|mesh-terms=* Aldosterone
* Animals
* Bone and Bones
* Cardiovascular Diseases
* Disease Models, Animal
* Female
* Fibroblast Growth Factors
* Gene Knockout Techniques
* Glucuronidase
* Kidney
* Longevity
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Osteoblasts
* Protein Isoforms
* Transcriptome
|keywords=* Bone Biology
* Cardiovascular disease
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962016
}}
{{medline-entry
|title=Fibroblast growth factor 23 and symmetric dimethylarginine concentrations in geriatric cats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31568615
|abstract=Fibroblast growth factor 23 ([[FGF23]]) is a phosphaturic hormone that is increased in azotemic cats with chronic kidney disease (CKD) and predictive of the onset of azotemia in older cats. The introduction of symmetric dimethylarginine (SDMA) as a biomarker of glomerular filtration rate has led to the identification of cats in which SDMA is increased, but plasma creatinine concentrations remains within reference range. There is currently little understanding of the metabolic changes present in such cats. To examine the relationship between plasma [[FGF23]] and SDMA concentrations in non-azotemic geriatric cats. Records of a cross section of client-owned cats (n = 143) without azotemic CKD. Clinicopathological information was obtained from cats (≥ 9 years) from records of 2 first opinion practices. The relationship between plasma SDMA and [[FGF23]] concentrations was examined using Spearman's correlation and variables compared using the Mann-Whitney U test. Cats with increased SDMA concentrations had significantly higher plasma [[FGF23]] (P < .001) and creatinine (P < .001) concentrations compared to cats with SDMA concentrations within reference range. A weak positive relationship was demonstrated between plasma [[FGF23]] and SDMA concentrations (r = .35, P < .001) and between plasma [[FGF23]] and creatinine (r = .23, P = .005) concentrations. More cats with increased SDMA concentrations had higher [[FGF23]] concentrations than those with SDMA concentrations within the reference range, suggesting the presence of an alteration in phosphate homeostasis. Further studies are warranted to identify influencing factors and to explore the utility of [[FGF23]] concentration to inform management of cats with early stage CKD.
|mesh-terms=* Aging
* Animals
* Arginine
* Biomarkers
* Cats
* Cross-Sectional Studies
* Female
* Fibroblast Growth Factors
* Male
* Reference Values
* Retrospective Moral Judgment
|keywords=* azotemia
* feline
* phosphate
* renal
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872607
}}
{{medline-entry
|title=Muscle-bone crosstalk and potential therapies for sarco-osteoporosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31106446
|abstract=The nature of muscle-bone crosstalk has been historically considered to be only mechanical, where the muscle is the load applier while bone provides the attachment sites. However, this dogma has been challenged with the emerging notion that bone and muscle act as secretory endocrine organs affect the function of each other. Biochemical crosstalk occurs through myokines such as myostatin, irisin, interleukin (IL)-6, IL-7, IL-15, insulin-like growth factor-1, fibroblast growth factor (FGF)-2, and β-aminoisobutyric acid and through bone-derived factors including [[FGF23]], prostaglandin E , transforming growth factor β, osteocalcin, and sclerostin. Aside from the biochemical and mechanical interaction, additional factors including aging, circadian rhythm, nervous system network, nutrition intake, and exosomes also have effects on bone-muscle crosstalk. Here, we summarize the current research progress in the area, which may be conductive to identify potential novel therapies for the osteoporosis and sarcopenia, especially when they develop in parallel.
|mesh-terms=* Aging
* Bone and Bones
* Circadian Rhythm
* Humans
* Muscle Proteins
* Muscle, Skeletal
* Nervous System Physiological Phenomena
* Osteocalcin
* Protein Binding
* Signal Transduction
|keywords=* bone
* crosstalk
* muscle
* myokines
* osteoporosis
* sarcopenia
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331460
}}
{{medline-entry
|title=Extraskeletal Calcifications in Hutchinson-Gilford Progeria Syndrome.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31077852
|abstract=Children with Hutchinson-Gilford progeria syndrome (HGPS), a rare premature aging disease, exhibit extraskeletal calcifications detected by radiographic analysis and on physical examination. The aim of this study was to describe the natural history and pathophysiology of these abnormal calcifications in HGPS, and to determine whether medications and/or supplements tested in clinical trials alter their development. Children from two successive clinical trials administering 1) lonafarnib (n = 26) and 2) lonafarnib   pravastatin   zoledronic acid (n = 37) were studied at baseline (pre-therapy), one year on therapy, and at end-of-therapy (3.3-4.3 years after the baseline visit). Calcium supplementation (oral calcium carbonate) was administered during the first year of the second trial and was subsequently discontinued. Information on calcifications was obtained from physical examinations, radiographs, and serum and urinary biochemical measures. The mineral content of two skin-derived calcifications was determined by x-ray diffraction. Extraskeletal calcifications were detected radiographically in 12/39 (31%) patients at baseline. The odds of exhibiting calcifications increased with age (p = 0.045). The odds were unaffected by receipt of lonafarnib, pravastatin, and zoledronate therapies. However, administration of calcium carbonate supplementation, in conjunction with all three therapeutic agents, significantly increased the odds of developing calcifications (p = 0.009), with the odds plateauing after the supplement's discontinuation. Composition analysis of calcinosis cutis showed hydroxyapatite similar to bone. Although serum calcium, phosphorus, and parathyroid hormone ([[PTH]]) were within normal limits at baseline and on-therapy, [[PTH]] increased significantly after lonafarnib initiation (p < 0.001). Both the urinary calcium/creatinine ratio and tubular reabsorption of phosphate (TRP) were elevated at baseline in 22/39 (56%) and 31/37 (84%) evaluable patients, respectively, with no significant changes while on-therapy. The mean calcium × phosphorus product (Ca × Pi) was within normal limits, but plasma magnesium decreased over both clinical trials. Fibroblast growth factor 23 ([[FGF23]]) was lower compared to age-matched controls (p = 0.03). Extraskeletal calcifications increased with age in children with HGPS and were composed of hydroxyapatite. The urinary calcium/creatinine ratio and TRP were elevated for age while [[FGF23]] was decreased. Magnesium decreased and [[PTH]] increased after lonafarnib therapy which may alter the ability to mobilize calcium. These findings demonstrate that children with HGPS with normal renal function and an unremarkable Ca × Pi develop extraskeletal calcifications by an unidentified mechanism that may involve decreased plasma magnesium and [[FGF23]]. Calcium carbonate accelerated their development and is, therefore, not recommended for routine supplementation in these children.
|mesh-terms=* Calcinosis
* Calcium
* Child
* Child, Preschool
* Creatinine
* Female
* Humans
* In Vitro Techniques
* Lamin Type A
* Male
* Parathyroid Hormone
* Piperidines
* Pravastatin
* Progeria
* Pyridines
* Zoledronic Acid
|keywords=* Aging
* Extraskeletal calcifications
* HGPS
* Lamin
* Laminopathy
* Magnesium
* Parathyroid hormone
* Progeria
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628204
}}
{{medline-entry
|title=Genome-wide associations and detection of potential candidate genes for direct genetic and maternal genetic effects influencing dairy cattle body weight at different ages.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30727969
|abstract=Body weight (BW) at different ages are of increasing importance in dairy cattle breeding schemes, because of their strong correlation with energy efficiency traits, and their impact on cow health, longevity and farm economy. In total, 15,921 dairy cattle from 56 large-scale test-herds with BW records were genotyped for 45,613 single nucleotide polymorphisms (SNPs). This dataset was used for genome-wide association studies (GWAS), in order to localize potential candidate genes for direct and maternal genetic effects on BW recorded at birth (BW0), at 2 to 3 months of age (BW23), and at 13 to 14 months of age (BW1314). The first 20 principal components ([[PC]]) of the genomic relationship matrix ([Formula: see text]) grouped the genotyped cattle into three clusters. In the statistical models used for GWAS, correction for population structure was done by including polygenic effects with various genetic similarity matrices, such as the pedigree-based relationship matrix ([Formula: see text]), the [Formula: see text]-matrix, the reduced [Formula: see text]-matrix LOCO (i.e. exclusion of the chromosome on which the candidate SNP is located), and LOCO plus chromosome-wide [[PC]]. Inflation factors for direct genetic effects using [Formula: see text] and LOCO were larger than 1.17. For [Formula: see text] and LOCO plus chromosome-wide [[PC]], inflation factors were very close to 1.0. According to Bonferroni correction, ten, two and seven significant SNPs were detected for the direct genetic effect on BW0, BW23, and BW1314, respectively. Seventy-six candidate genes contributed to direct genetic effects on BW with four involved in growth and developmental processes: [[FGF6]], [[FGF23]], [[TNNT3]], and [[OMD]]. For maternal genetic effects on BW0, only three significant SNPs (according to Bonferroni correction), and four potential candidate genes, were identified. The most significant SNP on chromosome 19 explained only 0.14% of the maternal de-regressed proof variance for BW0. For correction of population structure in GWAS, we suggest a statistical model that considers LOCO plus chromosome-wide [[PC]]. Regarding direct genetic effects, several SNPs had a significant effect on BW at different ages, and only two SNPs on chromosome 5 had a significant effect on all three BW traits. Thus, different potential candidate genes regulate BW at different ages. Maternal genetic effects followed an infinitesimal model.
|mesh-terms=* Aging
* Animals
* Body Weight
* Cattle
* Extracellular Matrix Proteins
* Female
* Fibroblast Growth Factors
* Genome-Wide Association Study
* Male
* Polymorphism, Single Nucleotide
* Proteoglycans
* Quantitative Trait Loci
* Troponin T

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366057
}}
{{medline-entry
|title=Age-Related Changes and Effects of Bisphosphonates on Bone Turnover and Disease Progression in Fibrous Dysplasia of Bone.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30645769
|abstract=Fibrous dysplasia (FD) is a mosaic disease in which bone is replaced with fibro-osseous tissue. Lesions expand during childhood, reaching final burden by age 15 years. In vitro data suggest that disease activity decreases in adulthood; however, there is no clinical data to support this concept. Bone turnover markers (BTMs) have been used as markers of disease activity in FD; however, the natural history of BTM changes, the effects of antiresorptive treatment, and their association to clinical outcomes have not been described. The goals of this study are to describe 1) the natural history of FD disease activity and its association with pain; 2) the impact of bisphosphonates on the natural history of BTMs; and 3) the effect of bisphosphonates on progression of FD burden during childhood. Disease burden scores and alkaline phosphatase, osteocalcin, NTx, [[FGF23]], and RANKL levels from 178 subjects in an FD/MAS natural history study were reviewed, including 73 subjects treated with bisphosphonates. BTMs, RANKL, and [[FGF23]] demonstrated a sustained reduction with age. Bisphosphonate treatment did not significantly impact this age-dependent decrease in BTMs. Pain was more prevalent and severe in adults compared with children and was not associated with BTMs. In children, the progression of disease burden was not affected by bisphosphonates. In conclusion, FD is associated with an age-dependent decline in bone turnover and other markers of disease activity. Pain, in contrast, is more frequent and severe in adults with FD and is not related to bone turnover. Bisphosphonate treatment does not significantly impact the age-dependent decrease in bone turnover, nor does it prevent the progression of FD disease burden in children. These findings, in association with the established adverse effects of antiresorptives, should be considered when evaluating use and response to bisphosphonates in patients being treated for FD and in any study using BTMs as surrogate endpoints. © 2019 American Society for Bone and Mineral Research.
|mesh-terms=* Adolescent
* Adult
* Age Factors
* Aged
* Aged, 80 and over
* Aging
* Biomarkers
* Bone Remodeling
* Child
* Child, Preschool
* Diphosphonates
* Female
* Fibrous Dysplasia of Bone
* Humans
* Male
* Middle Aged
* Pain
* Prevalence
|keywords=* ANTIRESORPTIVES
* BIOCHEMICAL MARKERS OF BONE TURNOVER
* FIBROUS DYSPLASIA
* MCCUNE-ALBRIGHT SYNDROME
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983318
}}
{{medline-entry
|title=Kotho and aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30557478
|abstract=Three fibroblast growth factor(FGF) members, [[FGF19]], [[FGF21]], and [[FGF23]], function as endocrine factors that regulate various metabolic processes. The unique feature of these endo- crine FGFs is the fact that they require Klotho proteins to bind to their cognate FGF recep- tors. Defects in Klotho or [[FGF23]] result in disturbed mineral metabolism and accelerated aging. The aging phenotypes can be alleviated by correcting phosphate imbalance, leading us to hypothesize that phosphate accelerates aging. In contrast, overexpression of [[FGF21]] extends life span in mice. Thus, the FGF-Klotho endocrine axes have emerged as key regula- tors of the aging process and are regarded as potential therapeutic targets for the treatment of age-related disorders.
|mesh-terms=* Aging
* Animals
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Longevity
* Mice

}}
{{medline-entry
|title=The Klotho proteins in health and disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30455427
|abstract=The Klotho proteins, αKlotho and βKlotho, are essential components of endocrine fibroblast growth factor (FGF) receptor complexes, as they are required for the high-affinity binding of [[FGF19]], [[FGF21]] and [[FGF23]] to their cognate FGF receptors (FGFRs). Collectively, these proteins form a unique endocrine system that governs multiple metabolic processes in mammals. [[FGF19]] is a satiety hormone that is secreted from the intestine on ingestion of food and binds the βKlotho-[[FGFR4]] complex in hepatocytes to promote metabolic responses to feeding. By contrast, under fasting conditions, the liver secretes the starvation hormone [[FGF21]], which induces metabolic responses to fasting and stress responses through the activation of the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system following binding to the βKlotho-FGFR1c complex in adipocytes and the suprachiasmatic nucleus, respectively. Finally, [[FGF23]] is secreted by osteocytes in response to phosphate intake and binds to αKlotho-FGFR complexes, which are expressed most abundantly in renal tubules, to regulate mineral metabolism. Growing evidence suggests that the FGF-Klotho endocrine system also has a crucial role in the pathophysiology of ageing-related disorders, including diabetes, cancer, arteriosclerosis and chronic kidney disease. Therefore, targeting the FGF-Klotho endocrine axes might have therapeutic benefit in multiple systems; investigation of the crystal structures of FGF-Klotho-FGFR complexes is paving the way for the development of drugs that can regulate these axes.
|mesh-terms=* Aging
* Animals
* Biomarkers
* Birds
* Cardiovascular Diseases
* Endocrine System Diseases
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Hypothalamo-Hypophyseal System
* Kidney Diseases
* Mammals
* Phosphates
* Pituitary-Adrenal System

|full-text-url=https://sci-hub.do/10.1038/s41581-018-0078-3
}}
{{medline-entry
|title=Wnt signaling in bone, kidney, intestine, and adipose tissue and interorgan interaction in aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30101565
|abstract=Over the last two decades, it has become increasingly apparent that Wnt signaling plays a critical role in development and adult tissue homeostasis in multiple organs and in the pathogenesis of many diseases. In particular, a crucial role for Wnt signaling in bone development and bone tissue homeostasis has been well recognized. Numerous genome-wide association studies confirmed the importance of Wnt signaling in controlling bone mass. Moreover, ample evidence suggests that Wnt signaling is essential for kidney, intestine, and adipose tissue development and homeostasis. Recent emerging evidence demonstrates that Wnt signaling may play a fundamental role in the aging process of those organs. New discoveries show that bone is not only the major reservoir for calcium and phosphate storage, but also the largest organ with multiple functions, including mineral and energy metabolism. The interactions among bone, kidney, intestine, and adipose tissue are controlled and regulated by several endocrine signals, including [[FGF23]], klotho, sclerostin, osteocalcin, vitamin D, and leptin. Since the aging process is characterized by structural and functional decline in almost all tissues and organs, understanding the Wnt signaling-related interactions among bone, kidney, intestine, and adipose tissue in aging may shed light on the pathogenesis of age-related diseases.
|mesh-terms=* Adipose Tissue
* Aging
* Animals
* Bone Development
* Bone and Bones
* Humans
* Intestinal Mucosa
* Kidney
* Wnt Signaling Pathway
|keywords=* FGF23-klotho
* Wnt/β-catenin signaling
* aging
* bone
* sclerostin
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372353
}}
{{medline-entry
|title=Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30071357
|abstract=Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people at risk for increased vulnerability, disease, injury, and mortality. However, complementary molecular frailty biomarkers or ideally biomarker panels have not yet been identified. We conducted a systematic search to identify biomarker candidates for a frailty biomarker panel. Gene expression databases were searched (http://genomics.senescence.info/genes including GenAge, AnAge, LongevityMap, CellAge, DrugAge, Digital Aging Atlas) to identify genes regulated in aging, longevity, and age-related diseases with a focus on secreted factors or molecules detectable in body fluids as potential frailty biomarkers. Factors broadly expressed, related to several "hallmark of aging" pathways as well as used or predicted as biomarkers in other disease settings, particularly age-related pathologies, were identified. This set of biomarkers was further expanded according to the expertise and experience of the authors. In the next step, biomarkers were assigned to six "hallmark of aging" pathways, namely (1) inflammation, (2) mitochondria and apoptosis, (3) calcium homeostasis, (4) fibrosis, (5) NMJ (neuromuscular junction) and neurons, (6) cytoskeleton and hormones, or (7) other principles and an extensive literature search was performed for each candidate to explore their potential and priority as frailty biomarkers. A total of 44 markers were evaluated in the seven categories listed above, and 19 were awarded a high priority score, 22 identified as medium priority and three were low priority. In each category high and medium priority markers were identified. Biomarker panels for frailty would be of high value and better than single markers. Based on our search we would propose a core panel of frailty biomarkers consisting of (1) [[CXCL10]] (C-X-C motif chemokine ligand 10), IL-6 (interleukin 6), [[CX3CL1]] (C-X3-C motif chemokine ligand 1), (2) [[GDF15]] (growth differentiation factor 15), [[FNDC5]] (fibronectin type III domain containing 5), vimentin (VIM), (3) regucalcin (RGN/SMP30), calreticulin, (4) [[PLAU]] (plasminogen activator, urokinase), [[AGT]] (angiotensinogen), (5) [[BDNF]] (brain derived neurotrophic factor), progranulin (PGRN), (6) α-klotho (KL), [[FGF23]] (fibroblast growth factor 23), [[FGF21]], leptin (LEP), (7) miRNA (micro Ribonucleic acid) panel (to be further defined), [[AHCY]] (adenosylhomocysteinase) and [[KRT18]] (keratin 18). An expanded panel would also include (1) pentraxin (PTX3), sVCAM/ICAM (soluble vascular cell adhesion molecule 1/Intercellular adhesion molecule 1), defensin α, (2) [[APP]] (amyloid beta precursor protein), LDH (lactate dehydrogenase), (3) [[S100B]] (S100 calcium binding protein B), (4) TGFβ (transforming growth factor beta), PAI-1 (plasminogen activator inhibitor 1), [[TGM2]] (transglutaminase 2), (5) sRAGE (soluble receptor for advanced glycosylation end products), [[HMGB1]] (high mobility group box 1), C3/C1Q (complement factor 3/1Q), ST2 (Interleukin 1 receptor like 1), agrin (AGRN), (6) IGF-1 (insulin-like growth factor 1), resistin (RETN), adiponectin (ADIPOQ), ghrelin (GHRL), growth hormone (GH), (7) microparticle panel (to be further defined), GpnmB (glycoprotein nonmetastatic melanoma protein B) and lactoferrin (LTF). We believe that these predicted panels need to be experimentally explored in animal models and frail cohorts in order to ascertain their diagnostic, prognostic and therapeutic potential.
|mesh-terms=* Aged
* Aging
* Amyloid beta-Peptides
* Amyloid beta-Protein Precursor
* Animals
* Apoptosis
* Biomarkers
* Fibronectins
* Frailty
* Genetic Association Studies
* Growth Differentiation Factor 15
* Humans
* Insulin-Like Growth Factor I
* Interleukin-1 Receptor-Like 1 Protein
* Membrane Glycoproteins
* MicroRNAs
* Signal Transduction
|keywords=* Age-related diseases
* Biomarker panel
* Frailty
* Hallmark of aging pathways
|full-text-url=https://sci-hub.do/10.1016/j.arr.2018.07.004
}}
{{medline-entry
|title=New Insights into the Mechanism of Action of Soluble Klotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29250031
|abstract=The [i]klotho[/i] gene encodes a type I single-pass transmembrane protein that contains a large extracellular domain, a membrane spanning segment, and a short intracellular domain. Klotho protein exists in several forms including the full-length membrane form (mKl) and a soluble circulating form [soluble klotho (sKl)]. mKl complexes with fibroblast growth factor receptors to form coreceptors for [[FGF23]], which allows it to participate in [[FGF23]]-mediated signal transduction and regulation of phosphate and calcium homeostasis. sKl is present in the blood, urine, and cerebrospinal fluid where it performs a multitude of functions including regulation of ion channels/transporters and growth factor signaling. How sKl exerts these pleiotropic functions is poorly understood. One hurdle in understanding sKl's mechanism of action as a "hormone" has been the inability to identify a receptor that mediates its effects. In the body, the kidneys are a major source of sKl and sKl levels decline during renal disease. sKl deficiency in chronic kidney disease makes the heart susceptible to stress-induced injury. Here, we summarize the current knowledge of mKl's mechanism of action, the mechanistic basis of sKl's protective, [[FGF23]]-independent effects on the heart, and provide new insights into the mechanism of action of sKl focusing on recent findings that sKl binds sialogangliosides in membrane lipid rafts to regulate growth factor signaling.

|keywords=* FGF23
* IGF-1
* TRPC6
* aging
* heart disease
* klotho
* lipid rafts
* sialidase
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715364
}}
{{medline-entry
|title=The relevance of α-[[KL]]OTHO to the central nervous system: Some key questions.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28323064
|abstract=α-Klotho is well described as an anti-aging protein, with critical roles in kidney function as a transmembrane co-receptor for [[FGF23]], and as a soluble factor in serum. α-Klotho is also expressed in the choroid plexus, where it is released into the cerebrospinal fluid. Nonetheless, α-Klotho is also expressed in the brain parenchyma. Accumulating evidence indicates that this pool of α-Klotho, which we define as brain α-Klotho, may play important roles as a neuroprotective factor and in promoting myelination, thereby supporting healthy brain aging. Here we summarize what is known about brain α-Klotho before focusing on the outstanding scientific questions related to its function. We believe there is a need for in vitro studies designed to distinguish between brain α-Klotho and other pools of α-Klotho, and for a greater understanding of the basic function of soluble α-Klotho. The mechanism by which the human [[KL]]-VS variant affects cognition also requires further elucidation. To help address these questions we suggest some experimental approaches that other laboratories might consider. In short, we hope to stimulate fresh ideas and encourage new research approaches that will allow the importance of α-Klotho for the aging brain to become clear.
|mesh-terms=* Aging
* Animals
* Brain
* Central Nervous System
* Cognition
* Fibroblast Growth Factors
* Glucuronidase
* Humans
|keywords=* Aging
* CNS
* Cognition
* KLOTHO
* Signaling
|full-text-url=https://sci-hub.do/10.1016/j.arr.2017.03.003
}}
{{medline-entry
|title=Fibroblast Growth Factor 23 and the Risk of Infection-Related Hospitalization in Older Adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28122946
|abstract=Within monocytes, 1,25-dihydroxyvitamin D [1,25(OH) D] is important for production of cathelicidins, which in turn, are critical for antibacterial action. Fibroblast growth factor 23 ([[FGF23]]) decreases 1,25(OH) D production and thus, could increase infection risk. We examined this possibility in 3141 community-dwelling adults ages ≥65 years old at baseline in the Cardiovascular Health Study using Cox proportional hazards models to examine the association between [[FGF23]] concentrations and first infection-related hospitalizations and determine whether associations differed by the presence of CKD (eGFR<60 ml/min per 1.73 m [[i]n[/i]=832] or urine albumin-to-creatinine ratio >30 mg/g [[i]n[/i]=577]). Mean±SD age of participants was 78±5 years old, 60% of participants were women, and the median plasma [[FGF23]] concentration was 70 (interquartile range, 53-99) relative units per milliliter. In fully adjusted models, higher [[FGF23]] concentrations associated with higher risk of first infection-related hospitalization (hazard ratio [HR], 1.11; 95% confidence interval [95% CI], 1.03 to 1.20 per doubling of [[FGF23]]) during a median follow-up of 8.6 years. In participants with or without CKD (defined by eGFR), [[FGF23]] concentration associated with first infection-related hospitalization with HRs of 1.24 (95% CI, 1.08 to 1.42) and 1.06 (95% CI, 0.97 to 1.17) per doubling of [[FGF23]], respectively ([i]P[/i]=0.13 for interaction). Associations did not differ between groups when stratified by urine albumin-to-creatinine ratio. In sensitivity analyses, the addition of serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone, and 24,25-dihydroxyvitamin D did not meaningfully change the estimates. In conclusion, in community-dwelling older adults, higher plasma [[FGF23]] concentrations independently associated with the risk of first infection-related hospitalization.
|mesh-terms=* Aged
* Bacterial Infections
* Female
* Fibroblast Growth Factors
* Hospitalization
* Humans
* Longitudinal Studies
* Male
* Prospective Studies
* Risk Factors
|keywords=* aging
* chronic kidney disease
* clinical epidemiology
* infection
* mineral metabolism
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373449
}}
{{medline-entry
|title=Reduction of calprotectin and phosphate during testosterone therapy in aging men: a randomized controlled trial.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28000180
|abstract=To investigate the effect of testosterone treatment on biomarkers calprotectin, fibroblast growth factor 23 ([[FGF23]]), soluble Klotho, phosphate, calcium, parathyroid hormone, creatinine and estimated glomerular filtration rate. Randomized, double-blinded, placebo-controlled study. Odense Androgen Study-the effect of Testim and training in hypogonadal men. Men aged 60-78 years old with a low normal concentration of free of bioavailable testosterone <7.3 nmol/L and waist circumference >94 cm recruited from 2008 to 2009 (N = 48) by advertisement. Participants were randomized to receive 5-10 g gel/50-100 mg testosterone (Testim , Ipsen, France) or 5-10 g gel/placebo. The plasma levels of calprotectin and phosphate were significantly reduced in the group receiving testosterone therapy (gel) compared to the placebo group (p < 0.05). Testosterone treatment did not have any significant effect on plasma levels of [[FGF23]] or soluble Klotho. The reduction in phosphate levels was inversely associated with bioavailable testosterone. Compared to the placebo group, 6 months of testosterone therapy (gel) reduced calprotectin and phosphate levels suggesting decreased inflammation and decreased cardiovascular risk.
|mesh-terms=* Aged
* Aging
* Androgens
* Double-Blind Method
* Female
* Follow-Up Studies
* Humans
* Leukocyte L1 Antigen Complex
* Male
* Middle Aged
* Phosphates
* Prognosis
* Risk Factors
* Testosterone
|keywords=* Biomarkers
* Calprotectin
* FGF23
* Klotho
* Phosphate
* Testosterone therapy
|full-text-url=https://sci-hub.do/10.1007/s40618-016-0597-3
}}
{{medline-entry
|title=Association between circulating fibroblast growth factor-23 and age-related cardiovascular-renal parameters in a healthy Chinese population.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27427468
|abstract=Previous studies showed that circulating fibroblast growth factor-23 ([[FGF23]]) is a new biomarker linked to cardiovascular and kidney diseases. Here, we explored the association between serum [[FGF23]] and aging-related cardiovascular-renal parameters in a healthy Chinese population. A total of 314 healthy participants aged 36-87 years were enrolled. Cardiovascular structure and function were assessed by the left ventricular ejection fraction, the ratio of early diastolic peak flow velocity to late diastolic peak flow velocity at the mitral leaflet tips, carotid intima-media thickness, the diameter of the bilateral common carotid artery, blood systolic peak and end diastolic velocities, which were measured by M-mode ultrasonography. Glomerular filtration rate was evaluated using the Chronic Kidney Disease Epidemiology Collaboration equation and Chronic Kidney Disease Epidemiology Collaboration equation for Asians. Serum [[FGF23]], 1, 25-dihydroxy vitamin D and parathyroid hormone were measured by enzyme-linked immunosorbent assay. For all participants, intima-media thickness/diameter of the bilateral common carotid artery gradually decreased with the progression from low to high [[FGF23]] concentration (P < 0.05). After adjusting for all possible confounders, [[FGF23]] remained significantly associated with intima-media thickness/diameter of the bilateral common carotid artery (P = 0.016). In women, serum [[FGF23]] was significantly associated with serum creatinine, cystatin C and estimated glomerular filtration rate in the Spearman correlation analysis. [[FGF23]] remained significantly associated with serum creatinine (P = 0.046) and estimated glomerular filtration rate (P = 0.034) after full adjustment. However, no such relationship was apparent in men. Serum [[FGF23]] was correlated with aging-related cardiovascular-renal parameters even in healthy people. Measurement of serum [[FGF23]] can provide valuable information to predict cardiovascular-renal function in healthy people, especially in older female adults. Geriatr Gerontol Int 2017; 17: 1221-1231.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Biomarkers
* Cardiovascular System
* Carotid Intima-Media Thickness
* China
* Female
* Fibroblast Growth Factors
* Glomerular Filtration Rate
* Healthy Volunteers
* Heart Function Tests
* Humans
* Kidney Function Tests
* Male
* Middle Aged
* Reference Values
|keywords=* age
* cardiovascular
* fibroblast growth factor-23
* parameters
* renal
|full-text-url=https://sci-hub.do/10.1111/ggi.12844
}}
{{medline-entry
|title=The [[FGF23]]/[[KL]]OTHO Regulatory Network and Its Roles in Human Disorders.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27125741
|abstract=The functions of Klotho ([[KL]]) are multifaceted and include the regulation of aging and mineral metabolism. It was originally identified as the gene responsible for premature aging-like symptoms in mice and was subsequently shown to function as a coreceptor in the fibroblast growth factor (FGF) 23 signaling pathway. The discovery of [[KL]] as a partner for [[FGF23]] led to significant advances in understanding of the molecular mechanisms underlying phosphate and vitamin D metabolism, and simultaneously clarified the pathogenic roles of the [[FGF23]] signaling pathway in human diseases. These novel insights led to the development of new strategies to combat disorders associated with the dysregulated metabolism of phosphate and vitamin D, and clinical trials on the blockade of [[FGF23]] signaling in X-linked hypophosphatemic rickets are ongoing. Molecular and functional insights on [[KL]] and [[FGF23]] have been discussed in this review and were extended to how dysregulation of the [[FGF23]]/[[KL]] axis causes human disorders associated with abnormal mineral metabolism.
|mesh-terms=* Animals
* Calcium
* Fibroblast Growth Factors
* Gene Expression
* Glucuronidase
* Homeostasis
* Humans
* Metabolic Diseases
* Minerals
* Mutation
* Phosphates
* Receptors, Fibroblast Growth Factor
* Renal Insufficiency, Chronic
* Signal Transduction
* Vitamin D
|keywords=* Aging
* FGF23
* Klotho
* Phosphate
* Vitamin D
|full-text-url=https://sci-hub.do/10.1016/bs.vh.2016.02.001
}}
{{medline-entry
|title=Wound healing delays in α-Klotho-deficient mice that have skin appearance similar to that in aged humans - Study of delayed wound healing mechanism.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27037022
|abstract=Skin atrophy and delayed wound healing are observed in aged humans; however, the molecular mechanism are still elusive. The aim of this study was to analyze the molecular mechanisms of delayed wound healing by aging using α-Klotho-deficient (kl/kl) mice, which have phenotypes similar to those of aged humans. The kl/kl mice showed delayed wound healing and impaired granulation formation compared with those in wild-type (WT) mice. The skin graft experiments revealed that delayed wound healing depends on humoral factors, but not on kl/kl skin tissue. The mRNA expression levels of cytokines related to acute inflammation including IL-1β, IL-6 and [[TNF]]-α were higher in wound lesions of kl/kl mice compared with the levels in WT mice by RT-PCR analysis. LPS-induced [[TNF]]-α production model using spleen cells revealed that [[TNF]]-α production was significantly increased in the presence of [[FGF23]]. Thus, higher levels of [[FGF23]] in kl/kl mouse may have a role to increase [[TNF]]-α production in would lesion independently of α-Klotho protein, and impair granulation formation and delay wound healing.
|mesh-terms=* Aging
* Animals
* Cytokines
* Disease Models, Animal
* Female
* Glucuronidase
* Humans
* Male
* Mice
* Mice, Knockout
* Mice, Transgenic
* Skin
* Species Specificity
* Treatment Outcome
* Wound Healing
|keywords=* FGF23
* Klotho
* TNF-α
* Wound healing
|full-text-url=https://sci-hub.do/10.1016/j.bbrc.2016.03.138
}}
{{medline-entry
|title=Partial Reversal of Tissue Calcification and Extension of Life Span following Ammonium Nitrate Treatment of Klotho-Deficient Mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26881935
|abstract=Klotho is required for the inhibitory effect of [[FGF23]] on 1,25(OH)2D3 formation and Klotho-hypomorphic mice (kl/kl) suffer from severe tissue calcification due to excessive 1,25(OH)2D3 formation with subsequent increase of Ca2 and phosphate concentrations and stimulation of osteogenic signaling. The excessive tissue calcification dramatically accelerates aging and leads to premature death of the animals. Osteogenic signaling in those mice is disrupted by treatment with NH4Cl, which prevents tissue calcification and early death of kl/kl mice. The present study explored whether the beneficial effects of NH4Cl treatment could be mimicked by NH4NO3 treatment. The kl/kl mice had free access to tap water either without or with addition of NH4NO3 (0.28 M) starting with the mating of the parental generation. Calcification of trachea, lung, kidney, stomach, heart and vessels was visualized by histology with von Kossa staining. Plasma phosphate concentration was determined utilizing photometry, blood gas and electrolytes utilizing a blood Gas and Chemistry Analysis System and plasma 1,25(OH)2D3 concentration with ELISA. In untreated kl/kl mice plasma 1,25(OH)2D3 and phosphate concentrations were elevated, and the mice suffered from marked calcification of all tissues analyzed. Untreated kl/kl mice further suffered from respiratory acidosis due to marked lung emphysema. NH4NO3-treatment decreased both, blood pCO2 and HCO3-, decreased calcification of trachea, lung, kidney, stomach, heart and vessels and increased the life span of kl/kl mice more than 1.7-fold (♂) or 1.6-fold (♀) without significantly affecting extracellular pH or plasma concentrations of 1,25(OH)2D3, Ca2 , phosphate, Na , and K . NH4NO3-treatment turns respiratory acidosis into metabolic acidosis and mitigates calcification thus leading to a substantial extension of kl/kl mice survival.
|mesh-terms=* Animals
* Calcinosis
* Female
* Glucuronidase
* Longevity
* Male
* Mice
* Mice, Knockout
* Nitrates
* Treatment Outcome

|full-text-url=https://sci-hub.do/10.1159/000443411
}}
{{medline-entry
|title=[Regulatory mechanism of circulating inorganic phosphate].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26813498
|abstract=Circulating level of phosphate is altered by age and diet, and is also controlled by several hormones such as parathyroid hormone([[PTH]]), 1,25-dihydroxyvitamin D[1,25(OH)2D]and fibroblast growth factor 23([[FGF23]]). The main function of [[PTH]] and 1,25(OH)2D is maintaining calcium homeostasis, while [[FGF23]] plays a central role in phosphate metabolism. [[PTH]] suppresses phosphate reabsorption in the proximal tubules to increase the renal phosphate wasting, while 1,25(OH)2D facilitates the intestinal phosphate absorption. [[FGF23]] increases the renal phosphate wasting and reduces the production of 1,25(OH)2D. Of note, these hormones mutually regulate one another. The production of [[FGF23]] is also regulated by various local factors. The mechanism for sensing the phosphate availability still remains unknown, and further investigation is required.
|mesh-terms=* Aging
* Animals
* Calcitriol
* Calcium
* Diet
* Fibroblast Growth Factors
* Homeostasis
* Humans
* Intestinal Absorption
* Kidney Tubules
* Parathyroid Hormone
* Phosphates

|full-text-url=https://sci-hub.do/CliCa1602193198
}}
{{medline-entry
|title=Biological Role of Anti-aging Protein Klotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26528423
|abstract=Klotho-deficient mice have accelerated aging phenotypes, whereas overexpression of Klotho in mice extends lifespan. Klotho is an anti-aging single-pass membrane protein predominantly produced in the kidney, with shedding of the amino-terminal extracellular domain into the systemic circulation. Circulating levels of soluble Klotho decrease with age, and the klotho gene is associated with increased risk of age-related diseases. The three forms of Klotho protein have distinct functions. Membrane Klotho forms a complex with fibroblast growth factor (FGF) receptors, functions as an obligatory co-receptor for [[FGF23]], which is involved in aging and the development of chronic diseases via regulation of P i and vitamin D metabolism. Secreted Klotho functions as a humoral factor with pleiotropic activities including regulation of oxidative stress, growth factor signaling, and ion homeostasis. Secreted Klotho is also involved in organ protection. The intracellular form of Klotho suppresses inflammation-mediated cellular senescence and mineral metabolism. Herein we provide a brief overview of the structure and function and recent research about Klotho.

|keywords=* Age-related diseases
* Aging
* Klotho
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608225
}}
{{medline-entry
|title=Soluble αKlotho as a candidate for the biomarker of aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26462468
|abstract=Although the Klotho gene has been recognized as an aging-suppressor gene, the significance of its soluble product, soluble αKlotho (sKlotho), in aging remains to be elucidated. To address this issue, we conducted a single-centered cross-sectional study in a region with a high prevalence of aging. We compared sKlotho levels with the patient characteristics from medical records and laboratory measurements, including fibroblast growth factor 23 ([[FGF23]]), intact parathyroid hormone, activated vitamin D3 and factors associated with mineral bone metabolism, in 52 outpatients with a mean age of 78.2 years. Serum sKlotho levels significantly decreased with age, but were not associated with the stage of chronic kidney disease (CKD). Serum [[FGF23]] levels increased as CKD stages advanced, but were not associated with aging. Univariate analyses revealed that sKlotho levels positively correlated with glomerular filtration rate, and negatively with age and serum levels of [[FGF23]] and phosphorus. In a multivariable linear regression analysis, sKlotho significantly correlated with aging and lower [[FGF23]] levels. Only osteoporosis affected sKlotho and [[FGF23]] levels among the various complications and patient status including medication. In summary, serum sKlotho levels inversely correlated with age and [[FGF23]], and were significantly reduced in patients with osteoporosis. sKlotho may serve as a biomarker of aging independent of renal function.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Biomarkers
* Female
* Glucuronidase
* Humans
* Male
* Solubility
|keywords=* Aging
* Chronic kidney disease
* FGF23
* Klotho
* Osteoporosis
* Soluble αKlotho
|full-text-url=https://sci-hub.do/10.1016/j.bbrc.2015.10.018
}}
{{medline-entry
|title=Acetazolamide sensitive tissue calcification and aging of klotho-hypomorphic mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26307633
|abstract=Klotho, a protein expressed mainly in the kidney, is required for the inhibitory effect of [[FGF23]] on renal 1,25(OH)2D3 formation. Klotho counteracts vascular calcification and diverse age-related disorders. Klotho-hypomorphic mice (kl/kl) suffer from severe vascular calcification and rapid aging. The calcification is at least in part caused by excessive 1,25(OH)2D3, Ca(2 ), and phosphate concentrations in blood, which trigger osteogenic signaling including upregulation of alkaline phosphatase (Alpl). As precipitation of calcium and phosphate is fostered by alkaline pH, extracellular acidosis could counteract tissue calcification. In order to induce acidosis, acetazolamide was added to drinking water (0.8 g/l) of kl/kl and wild-type mice. As a result, acetazolamide treatment of kl/kl mice partially reversed the growth deficit, tripled the life span, almost completely reversed the calcifications in trachea, lung, kidney, stomach, intestine, and vascular tissues, the excessive aortic alkaline phosphatase mRNA levels and the plasma concentrations of osteoprotegerin, osteopontin as well as fetuin-A, without significantly decreasing [[FGF23]], 1,25(OH)2D3, Ca(2 ), and phosphate plasma concentrations. In primary human aortic smooth muscle cells, acidotic environment prevented phosphate-induced alkaline phosphatase mRNA expression. The present study reveals a completely novel effect of acetazolamide, i.e., interference with osteoinductive signaling and tissue calcification in kl/kl mice. Klotho deficient (kl/kl) mice suffer from hyperphosphatemia with dramatic tissue calcification. Acetazolamide (ACM) treatment partially reversed the growth deficit of kl/kl mice. In kl/kl mice, ACM reversed tissue calcification despite continued hyperphosphatemia. ACM tripled the life span of kl/kl mice. In human aortic smooth muscle cells, low extracellular pH prevented osteogenic signaling.
|mesh-terms=* Acetazolamide
* Acidosis
* Aging
* Alkaline Phosphatase
* Animals
* Calcitriol
* Calcium
* Carbonic Anhydrase Inhibitors
* Cells, Cultured
* Glucuronidase
* Humans
* Hyperphosphatemia
* Mice
* Mice, Knockout
* Osteogenesis
* Phosphates
* Signal Transduction
* Vascular Calcification
|keywords=* 1,25(OH)2D3
* Acetazolamide
* Acidosis
* Calcification
* Calcium
* Phosphate
|full-text-url=https://sci-hub.do/10.1007/s00109-015-1331-x
}}
{{medline-entry
|title=N-ethyl-N-Nitrosourea (ENU) induced mutations within the klotho gene lead to ectopic calcification and reduced lifespan in mouse models.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25860694
|abstract=Ectopic calcification (EC), which is the pathological deposition of calcium and phosphate in extra-skeletal tissues, may be associated with hypercalcaemic and hyperphosphataemic disorders, or it may occur in the absence of metabolic abnormalities. In addition, EC may be inherited as part of several monogenic disorders and studies of these have provided valuable insights into the metabolic pathways regulating mineral metabolism. For example, studies of tumoural calcinosis, a disorder characterised by hyperphosphataemia and progressive EC, have revealed mutations of fibroblast growth factor 23 ([[FGF23]]), polypeptide N-acetyl galactosaminyltransferase 3 (GALNT3) and klotho (KL), which are all part of a phosphate-regulating pathway. However, such studies in humans are limited by the lack of available large families with EC, and to facilitate such studies we assessed the progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) for EC. This identified two mutants with autosomal recessive forms of EC, and reduced lifespan, designated Ecalc1 and Ecalc2. Genetic mapping localized the Ecalc1 and Ecalc2 loci to a 11.0 Mb region on chromosome 5 that contained the klotho gene (Kl), and DNA sequence analysis identified nonsense (Gln203Stop) and missense (Ile604Asn) Kl mutations in Ecalc1 and Ecalc2 mice, respectively. The Gln203Stop mutation, located in KL1 domain, was severely hypomorphic and led to a 17-fold reduction of renal Kl expression. The Ile604Asn mutation, located in KL2 domain, was predicted to impair klotho protein stability and in vitro expression studies in COS-7 cells revealed endoplasmic reticulum retention of the Ile604Asn mutant. Further phenotype studies undertaken in Ecalc1 (kl203X/203X) mice demonstrated elevations in plasma concentrations of phosphate, [[FGF23]] and 1,25-dihydroxyvitamin D. Thus, two allelic variants of Kl that develop EC and represent mouse models for tumoural calcinosis have been established.
|mesh-terms=* Alleles
* Amino Acid Sequence
* Animals
* COS Cells
* Calcinosis
* Chlorocebus aethiops
* Codon, Nonsense
* Disease Models, Animal
* Endoplasmic Reticulum
* Ethylnitrosourea
* Fibroblast Growth Factors
* Genetic Loci
* Genotype
* Glucuronidase
* Humans
* Kidney
* Longevity
* Male
* Mice
* Mice, Inbred C57BL
* Molecular Sequence Data
* Mutation, Missense
* N-Acetylgalactosaminyltransferases
* Phenotype
* Phosphates
* Polymorphism, Single Nucleotide
* Sequence Alignment
* Vitamin D

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393098
}}
{{medline-entry
|title=Intracellular signaling of the aging suppressor protein Klotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25601466
|abstract=The Klotho protein deficiency is known to participate in premature aging. As an aging suppressor, Klotho is an important molecule in aging processes and its overexpression results in longevity. Due to many reasons, the insulin/insulin-like growth factor-1 (IGF-1) has been considered as a key pathway in aging research. The Klotho gene is closely related to this pathway. The Klotho gene encodes a transmembrane protein that after cleavage is also found as a secreted protein. Importantly, its overexpression suppresses insulin/IGF-1 signaling and thus extends the lifespan. In addition, Klotho participates in the regulation of several other intracellular signaling pathways, including regulation of [[FGF23]] signaling, cAMP, PKC, transforming growth factor-β (TGF-β), p53/p21, and Wnt signaling. The aim of this review is to summarize current literature that shows the involvement of Klotho in the regulation of several intracellular pathways. The results of our review clearly indicate that Klotho participates in several intracellular signaling pathways, and by regulating them, Klotho is involved in aging and longevity.
|mesh-terms=* Aging, Premature
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Insulin
* Insulin-Like Growth Factor I
* Longevity
* Transforming Growth Factor beta
* Wnt Signaling Pathway

|full-text-url=https://sci-hub.do/10.2174/1566524015666150114111258
}}
{{medline-entry
|title=Tumour-associated osteomalacia and hypoglycaemia in a patient with prostate cancer: is Klotho involved?
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25406200
|abstract=Tumour-associated osteomalacia is a paraneoplastic syndrome caused by renal phosphate wasting, leading to severe hypophosphataemia. Excess of circulating fibroblast growth factor 23 ([[FGF23]]) is the likely cause, acting via the [[FGF23]]/α-Klotho coreceptor, a critical regulator of phosphate metabolism. The other possible effects of that complex in humans are still under investigation. We present a case of an 84-year-old Belgian man, presenting prostate cancer with bone metastases. From June 2010 to March 2013, he presented three episodes of disease progression. From January 2012, the patient developed a progressively marked dorsal kyphosis with significant hypophosphataemia. The calculated TRP (tubular reabsorption of phosphate) was decreased and the [[FGF23]] increased. Mid-March 2013, the patient died after a profound unconsciousness due to hypoglycaemia with hypothermia. We hypothesised that the two paraneoplastic manifestations of this patient (tumour-associated osteomalacia and refractory hypoglycaemia) were due to one cause chain with two main nodes-[[FGF23]] and its coreceptor Klotho..
|mesh-terms=* Aged, 80 and over
* Aging
* Biomarkers, Tumor
* Blood Glucose
* Fatal Outcome
* Glucuronidase
* Humans
* Hypoglycemia
* Hypophosphatemia
* Male
* Osteomalacia
* Paraneoplastic Syndromes
* Prostatic Neoplasms

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244358
}}
{{medline-entry
|title=Calpain 1 inhibitor BDA-410 ameliorates α-klotho-deficiency phenotypes resembling human aging-related syndromes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25080854
|abstract=Taking good care of elderly is a major challenge of our society, and thus identification of potential drug targets to reduce age-associated disease burden is desirable. α-klotho(-/-) (α-kl) is a short-lived mouse model that displays multiple phenotypes resembling human aging-related syndromes. Such ageing phenotype of α-kl(-/-) mice is associated with activation of a proteolytic enzyme, Calpain-1. We hypothesized that uncontrolled activation of calpain-1 might be causing age-related phenotypes in α-kl-deficient mice. We found that daily administration of BDA-410, a calpain-1 inhibitor, strikingly ameliorated multiple aging-related phenotypes. Treated mice showed recovery of reproductive ability, increased body weight, reduced organ atrophy, and suppression of ectopic calcifications, bone mineral density reduction, pulmonary emphysema and senile atrophy of skin. We also observed ectopic expression of [[FGF23]] in calcified arteries of α-kl(-/-) mice, which might account for the clinically observed association of increased [[FGF23]] level with increased risk of cardiovascular mortality. These findings allow us to propose that modulation of calpain-1 activity is a potential therapeutic option for delaying age-associated organ pathology, particularly caused by the dysregulation of mineral ion homeostasis.
|mesh-terms=* Aging
* Animals
* Calpain
* Drug Evaluation, Preclinical
* Female
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Male
* Mice, Knockout
* Phenotype
* Renal Insufficiency, Chronic
* Sulfonamides
* Vascular Calcification

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118420
}}
{{medline-entry
|title=[Bone metabolism and cardiovascular function update. α-klotho/[[FGF23]] system; a new insight into the field of mineral homeostasis and the pathogeneses of aging-associated syndromes and the complications of chronic kidney disease].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24976054
|abstract=α-klotho (α-kl) was first identified as an aging gene and was later shown to be a regulator of mineral homeostasis. α-kl (- / -) mice display multiple aging related phenotypes including atherosclerosis, cardiovascular/soft tissue calcifications, pulmonary emphysema, osteopenia, and senile atrophy of skin ; such age-related organ pathologies are associated with biochemical changes in blood, including severe hyperphosphatemia, elevated serum [[FGF23]] and1,25 (OH) 2 Vitamin D levels. Of significance, advanced stage patients suffering chronic kidney disease (CKD) develop multiple complications quite resembling phenotypes observed in α-kl (- / -) mice, and high serum phosphate, the major cause of abnormalities of α-kl (- / -) mice, has been reported to be closely associated with high levels of cardiovascular disease morbidity and mortality in patients with CKD, particularly in patients with end-stage renal disease. In addition, the expressions of α-kl mRNA and α-Kl protein were severely reduced in these patients. These results suggest the involvement of α-Kl and [[FGF23]] in the pathogeneses of not only aging-associated syndromes but also the complications of CKD. Here, the unveiling of the molecular functions of α-Klotho and [[FGF23]] has recently given new insight into the field of mineral homeostasis and the pathogeneses of aging-associated syndromes and the complications of CKD.
|mesh-terms=* Aging
* Animals
* Bone Density
* Bone and Bones
* Cardiovascular Diseases
* Fibroblast Growth Factors
* Glucuronidase
* Homeostasis
* Humans
* Renal Insufficiency, Chronic

|full-text-url=https://sci-hub.do/CliCa140710051011
}}
{{medline-entry
|title=[Aging and inflammation: Klotho, diet and the kidney connection].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24294726
|abstract=Despite renal replacement therapy mortality among chronic kidney disease patients is 10-1000-fold higher than in age-matched controls. Klotho is a kidney protein with anti-ageing hormonal properties that is also a co-receptor for the [[FGF23]] fosfatonin. There is a bidirectional relationship between Klotho and inflammation. Thus, inflammation decreases renal Klotho and Klotho has anti-inflammatory properties. Mice with genetic defects in Klotho suffer from accelerated aging and early death. Decreasing the phosphate load improves the phenotype and prolongs survival in these mice. Unraveling the Klotho-phosphate-inflammation interaction may open new avenues for research that may improve the outcomes of kidney patients as well as provide new tools to retard aging in the general population.
|mesh-terms=* Aging
* Animals
* Diet
* Glucuronidase
* Humans
* Inflammation
* Mice
* Renal Insufficiency, Chronic

}}
{{medline-entry
|title=Significance of the anti-aging protein Klotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24124751
|abstract=The Klotho gene was identified as an 'aging suppressor' in mice. Overexpression of the Klotho gene extends lifespan and defective Klotho results in rapid aging and early death. Both the membrane and secreted forms of Klotho have biological activity that include regulatory effects on general metabolism and a more specific effect on mineral metabolism that correlates with its effect on aging. Klotho serves as a co-receptor for fibroblast growth factor (FGF), but it also functions as a humoral factor that regulates cell survival and proliferation, vitamin D metabolism, and calcium and phosphate homeostasis and may serve as a potential tumor suppressor. Moreover, Klotho protects against several pathogenic processes in a [[FGF23]]-independent manner. These processes include cancer metastasis, vascular calcification, and renal fibrosis. This review covers the recent advances in Klotho research and discusses novel Klotho-dependent mechanisms that are clinically relevant in aging and age-related diseases.
|mesh-terms=* Aging
* Animals
* Calcium
* Cell Proliferation
* Cell Survival
* Fibroblast Growth Factors
* Glucuronidase
* Homeostasis
* Humans
* Kidney Diseases
* Membrane Proteins
* Mice
* Neoplasm Metastasis
* Neoplasms
* Phosphates
* Signal Transduction
* Vascular Calcification

|full-text-url=https://sci-hub.do/10.3109/09687688.2013.837518
}}
{{medline-entry
|title=[[FGF23]] affects the lineage fate determination of mesenchymal stem cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24068282
|abstract=[[FGF23]] is a bone-derived hormone that regulates mineral metabolism by inhibiting renal tubular phosphate reabsorption and suppressing circulating 1,25(OH)2D and [[PTH]] levels. These effects are mediated by FGF-receptor binding and activation in the presence of its coreceptor Klotho, which is expressed in the distal tubules of the kidney. Recently, expression of Klotho in skeletal tissues has been reported, indicating a direct, yet unclear, extrarenal effect of [[FGF23]] on cells involved with bone development and remodeling. In the present study, we found that bone marrow stromal cells harvested from Klotho null mice developed fewer osteoblastic but more adipocytic colonies than cells from wild-type mice. The underlying mechanism was explored by experiments on mouse C3H10T1/2 cells. We found that Klotho was weakly expressed and that [[FGF23]] dose-dependently affected the lineage fate determination. The effects of [[FGF23]] on cell differentiation can be diminished by SU 5402, a specific tyrosine kinase inhibitor for FGF receptors. Our results indicate that [[FGF23]] directly affects the differentiation of bone marrow stromal cells.
|mesh-terms=* Adipocytes
* Aging
* Animals
* Bone and Bones
* Cell Differentiation
* Cell Lineage
* Cell Proliferation
* Dose-Response Relationship, Drug
* Fibroblast Growth Factors
* Gene Expression Regulation
* Glucuronidase
* Kidney Tubules
* Mesenchymal Stem Cells
* Mice
* Mice, Inbred C3H
* Osteoblasts
* Osteoporosis
* Phosphates
* Protein Binding
* Recombinant Proteins

|full-text-url=https://sci-hub.do/10.1007/s00223-013-9795-6
}}
{{medline-entry
|title=Klotho and chronic kidney disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23652549
|abstract=Through alternative splicing, Klotho protein exists both as a secreted and a membrane form whose extracellular domain could be shed from the cell surface by secretases and released into the circulation to act as endocrine factor. Unlike membrane Klotho which functions as a coreceptor for fibroblast growth factor-23 ([[FGF23]]) to modulate [[FGF23]] signal transduction, soluble Klotho is a multifunction protein present in the biological fluids including blood, urine and cerebrospinal fluid and plays important roles in antiaging, energy metabolism, inhibition of Wnt signaling, antioxidation, modulation of ion transport, control of parathyroid hormone and 1,25(OH)2VD3 production, and antagonism of renin-angiotensin-aldosterone system. Emerging evidence from clinical and basic studies reveal that chronic kidney disease is a state of endocrine and renal Klotho deficiency, which may serve as an early biomarker and a pathogenic contributor to chronic progression and complications in chronic kidney disease including vascular calcification, cardiac hypertrophy, and secondary hyperparathyroidism. Supplementation of exogenous Klotho and/or upregulation of endogenous Klotho production by using rennin angiotensin system inhibitors, HMG CoA reductase inhibitors, vitamin D analogues, peroxisome proliferator-activated receptors-gamma agonists, or anti-oxidants may confer renoprotection from oxidation and suppression of renal fibrosis, and also on prevention or alleviation of complications in chronic kidney disease. Therefore, Klotho is a highly promising candidate on the horizon as an early biomarker, and as a novel therapeutic agent for chronic kidney disease.
|mesh-terms=* Aging
* Animals
* Calcinosis
* Calcium
* Cardiomyopathies
* Chronic Kidney Disease-Mineral and Bone Disorder
* Disease Models, Animal
* Disease Progression
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Hyperparathyroidism, Secondary
* Membrane Proteins
* Nephrosclerosis
* Parathyroid Hormone
* Phosphates
* Renal Insufficiency, Chronic
* Renin-Angiotensin System
* Signal Transduction
* Solubility
* Uremia
* Vitamin D

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911771
}}
{{medline-entry
|title=Klotho and βKlotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22396160
|abstract=Endocrine fibroblast growth factors (FGFs) have been recognized as hormones that regulate a variety of metabolic processes. [[FGF19]] is secreted from intestine upon feeding and acts on liver to suppress bile acid synthesis. [[FGF21]] is secreted from liver upon fasting and acts on adipose tissue to promote lipolysis and responses to fasting. [[FGF23]] is secreted from bone and acts on kidney to inhibit phosphate reabsorption and vitamin D synthesis. One critical feature of endocrine FGFs is that they require the Klotho gene family of transmembrane proteins as coreceptors to bind their cognate FGF receptors and exert their biological activities. This chapter overviews function of Klotho family proteins as obligate coreceptors for endocrine FGFs and discusses potential link between Klothos and age-related diseases.
|mesh-terms=* Aging
* Animals
* Glucuronidase
* Homeostasis
* Humans
* Membrane Proteins
* Phosphates
* Receptors, Cytoplasmic and Nuclear

|full-text-url=https://sci-hub.do/10.1007/978-1-4614-0887-1_2
}}
{{medline-entry
|title=Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21982773
|abstract=Isoforms of the mammalian klotho protein serve as membrane co-receptors that regulate renal phosphate and calcium reabsorption. Phosphaturic effects of klotho are mediated in cooperation with fibroblast growth factor receptor-1 and its [[FGF23]] ligand. The vitamin D receptor and its 1,25-dihydroxyvitamin D(3) ligand are also crucial for calcium and phosphate regulation at the kidney and participate in a feedback loop with [[FGF23]] signaling. Herein we characterize vitamin D receptor-mediated regulation of klotho mRNA expression, including the identification of vitamin D responsive elements ([[VDR]]Es) in the vicinity of both the mouse and human klotho genes. In keeping with other recent studies of vitamin D-regulated genes, multiple [[VDR]]Es control klotho expression, with the most active elements located at some distance (-31 to -46 kb) from the klotho transcriptional start site. We therefore postulate that the mammalian klotho gene is up-regulated by liganded [[VDR]] via multiple remote [[VDR]]Es. The phosphatemic actions of 1,25-dihydroxyvitamin D(3) are thus opposed via the combined phosphaturic effects of [[FGF23]] and klotho, both of which are upregulated by the liganded vitamin D receptor.
|mesh-terms=* Aging
* Animals
* Cell Line
* Gene Expression Regulation
* Glucuronidase
* Humans
* Kidney
* Ligands
* Mice
* RNA, Messenger
* Receptors, Calcitriol
* Vitamin D
* Vitamin D Response Element

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209523
}}
{{medline-entry
|title=Identification of novel small molecules that elevate Klotho expression.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21939436
|abstract=The absence of Klotho ([[KL]]) from mice causes the development of disorders associated with human aging and decreased longevity, whereas increased expression prolongs lifespan. With age, [[KL]] protein levels decrease, and keeping levels consistent may promote healthier aging and be disease-modifying. Using the [[KL]] promoter to drive expression of luciferase, we conducted a high-throughput screen to identify compounds that activate [[KL]] transcription. Hits were identified as compounds that elevated luciferase expression at least 30%. Following validation for dose-dependent activation and lack of cytotoxicity, hit compounds were evaluated further in vitro by incubation with opossum kidney and Z310 rat choroid plexus cells, which express [[KL]] endogenously. All compounds elevated [[KL]] protein compared with control. To determine whether increased protein resulted in an in vitro functional change, we assayed [[FGF23]] (fibroblast growth factor 23) signalling. Compounds G-I augmented ERK (extracellular-signal-regulated kinase) phosphorylation in FGFR (fibroblast growth factor receptor)-transfected cells, whereas co-transfection with [[KL]] siRNA (small interfering RNA) blocked the effect. These compounds will be useful tools to allow insight into the mechanisms of [[KL]] regulation. Further optimization will provide pharmacological tools for in vivo studies of [[KL]].
|mesh-terms=* Aging
* Animals
* Cell Line
* Cloning, Molecular
* Drug Screening Assays, Antitumor
* Fibroblast Growth Factors
* Gene Expression Regulation
* Glucuronidase
* Kidney
* Mice
* Opossums
* Rats

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677209
}}
{{medline-entry
|title=The role of cellular senescence during vascular calcification: a key paradigm in aging research.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21235497
|abstract=Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events. Vascular calcification refers to the deposition of calcium phosphate mineral, most often hydroxyapatite, in arteries. Extensive calcification of the vascular system is a key characteristic of aging. In this article, we outline the mechanisms governing vascular calcification and highlight its association with cellular senescence. This review discusses the molecular mechanisms of cellular senescence and its affect on calcification of vascular cells, the relevance of phosphate regulation and the function of [[FGF23]] and Klotho proteins. The association of vascular calcification and cellular senescence with the rare human aging disorder Hutchison-Gilford Progeria Syndrome (HGPS) is highlighted and the mouse models used to try to determine the underlying pathways are discussed. By understanding the pathways involved in these processes novel drug targets may be elucidated in an effort to reduce the effects of cellular aging as a risk factor in cardiovascular disease.
|mesh-terms=* Aging
* Animals
* Calcinosis
* Cellular Senescence
* Durapatite
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Models, Animal
* Phosphates
* Vascular Diseases

|full-text-url=https://sci-hub.do/10.2174/1874609811104020128
}}
{{medline-entry
|title=Klotho interferes with a novel FGF-signalling pathway and insulin/Igf-like signalling to improve longevity and stress resistance in Caenorhabditis elegans.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20844315
|abstract=Klotho exerts anti-aging properties in mammals in two different ways. While membrane-bound Klotho, which is primarily expressed in the kidney, acts as an obligate co-receptor of [[FGF23]] to regulate phosphate homeostasis, secreted Klotho, resulting from the shedding of the KL1-KL2 ectodomain into the bloodstream, inhibits Insulin/IGF1 signalling. However, the underlying molecular mechanisms are not fully understood. Here, we investigated the biological role of Klotho in Caenorhabditis elegans. Two redundant homologues of the klotho gene exist in C. elegans and encode predicted proteins homologous to the  glucosidase-like KL1 domain of mammalian Klotho. We have used a genetic approach to investigate the functional activity of Klotho in C. elegans. Here, we report that whereas Klotho requires EGL-15 (FGFR) and EGL-17 to promote longevity and oxidative stress resistance, it is not involved in the regulation of fluid homeostasis, controlled by LET-756. Besides revealing a new post-developmental role for EGL-17, our data suggest that the KL1 form of Klotho is involved in [[FGF23]]-independent FGF signalling. We also report a genetic interaction between Klotho and the DAF-2 (Ins/IGF1R)/DAF-16 (FOXO) pathway. While the regulation of longevity requires functional DAF-2/DAF-16 signalling, the control of oxidative stress resistance involves a DAF-2- independent, DAF-16-dependent pathway, suggesting that Klotho may target either DAF-2 or DAF-16, depending of environmental conditions. Thus, the predictive KL1 form of Klotho appears to crosstalk with both FGF and Insulin/IGF1/FOXO pathways to exert anti-aging properties in C. elegans.
|mesh-terms=* Aging
* Amino Acid Sequence
* Animals
* Caenorhabditis elegans
* Caenorhabditis elegans Proteins
* Fibroblast Growth Factors
* Glucuronidase
* Insulin
* Insulin-Like Growth Factor I
* Intercellular Signaling Peptides and Proteins
* Longevity
* Models, Animal
* Molecular Sequence Data
* Receptor, Insulin
* Receptors, Fibroblast Growth Factor
* Signal Transduction
* Stress, Physiological
* Water-Electrolyte Balance

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2984606
}}
{{medline-entry
|title=Effect of sirolimus on calcineurin inhibitor-induced nephrotoxicity using renal expression of KLOTHO, an antiaging gene.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20562737
|abstract=The aim of this study was to observe the effect of sirolimus ([[SRL]]) on calcineurin inhibitor (CNI)-induced nephrotoxicity in the aging process by using renal expression of KLOTHO, an antiaging gene. METHODS.: Mice were treated with vehicle (VH; 1 mL/kg/day of olive oil), cyclosporine A (CsA; 30 mg/kg/day), or tacrolimus (FK; 1 mg/kg/day) with or without [[SRL]] (0.3 mg/kg/day) for 2 weeks. KLOTHO expression was evaluated by using reverse-transcriptase polymerase chain reaction, immunoblotting, and immunohistochemistry. Oxidative stress was evaluated by using immunohistochemistry and urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG). The calcium metabolism was evaluated by using renal ectopic calcification, serum intact parathyroid hormone level, and renal fibroblast factor 23 ([[FGF23]]) expression. Treatment with CsA or FK alone significantly decreased KLOTHO expression and increased urinary 8-OHdG excretion compared with VH treatment but [[SRL]] treatment did not. Treatment [[SRL]] CsA or [[SRL]] FK further decreased KLOTHO expression and increased urinary 8-OHdG excretion compared with treatment of CsA or FK alone. There was a strong correlation between KLOTHO expression and urinary 8-OHdG excretion (r=-0.893; P<0.001). Treatment of CsA or FK alone increased renal ectopic calcification and serum intact parathyroid hormone level and decreased renal [[FGF23]] expression compared with VH treatment (P<0.05) but [[SRL]] treatment did not. Treatment with [[SRL]] CNI aggravated these parameters compared with CNI alone. [[SRL]] accelerates the CNI-induced oxidative process by down-regulating the renal antioxidant KLOTHO expression in the kidney.
|mesh-terms=* Aging
* Animals
* Calcineurin Inhibitors
* Colforsin
* Cyclosporine
* DNA Primers
* Gene Expression Regulation
* Glucuronidase
* Immunosuppressive Agents
* Kidney
* Mice
* Nephritis, Interstitial
* Oxidative Stress
* RNA
* RNA, Messenger
* Reverse Transcriptase Polymerase Chain Reaction
* Sirolimus
* Tacrolimus

|full-text-url=https://sci-hub.do/10.1097/TP.0b013e3181e117b4
}}
{{medline-entry
|title=Regulation of ion channels by secreted Klotho: mechanisms and implications.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20375979
|abstract=Klotho is an anti-aging protein predominantly expressed in the kidney, parathyroid glands, and choroid plexus of the brain. It is a single-pass transmembrane protein with a large extracellular domain. The extracellular domain of Klotho is cleaved and released into extracellular fluid, including blood, urine, and cerebrospinal fluid. The membrane-bound full-length Klotho and secreted extracellular domain of Klotho have distinct functions. Membrane Klotho interacts with fibroblast growth factor (FGF) receptors to form high-affinity receptors for [[FGF23]]. Secreted Klotho functions as a humoral factor that regulates several ion channels and transporters, and other processes, including insulin and insulin-like growth factor signaling. This mini-review focuses on the mechanisms of regulation of cell-surface abundance of ion channels by secreted Klotho and the importance of these effects of Klotho in physiology and pathological conditions.
|mesh-terms=* Aging
* Animals
* Cell Membrane
* Insulin
* Ion Channels
* Ions
* Kidney
* Mice
* Receptors, Fibroblast Growth Factor
* Signal Transduction

|full-text-url=https://sci-hub.do/10.1038/ki.2010.73
}}
{{medline-entry
|title=The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the "Fountain of Youth" to mediate healthful aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20227497
|abstract=The nuclear vitamin D receptor ([[VDR]]) binds 1,25-dihydroxyvitamin D3 (1,25D), its high affinity renal endocrine ligand, to signal intestinal calcium and phosphate absorption plus bone remodeling, generating a mineralized skeleton free of rickets/osteomalacia with a reduced risk of osteoporotic fractures. 1,25D/[[VDR]] signaling regulates the expression of [[TRPV6]], BGP, [[SPP1]], [[LRP5]], RANKL and OPG, while achieving feedback control of mineral ions to prevent age-related ectopic calcification by governing [[CYP24A1]], [[PTH]], [[FGF23]], [[PHEX]], and klotho transcription. Vitamin D also elicits numerous intracrine actions when circulating 25-hydroxyvitamin D3, the metabolite reflecting vitamin D status, is converted to 1,25D locally by extrarenal [[CYP27B1]], and binds [[VDR]] to promote immunoregulation, antimicrobial defense, xenobiotic detoxification, anti-inflammatory/anticancer actions and cardiovascular benefits. [[VDR]] also affects Wnt signaling through direct interaction with beta-catenin, ligand-dependently blunting beta-catenin mediated transcription in colon cancer cells to attenuate growth, while potentiating beta-catenin signaling via [[VDR]] ligand-independent mechanisms in osteoblasts and keratinocytes to function osteogenically and as a pro-hair cycling receptor, respectively. Finally, [[VDR]] also drives the mammalian hair cycle in conjunction with the hairless corepressor by repressing [[SOSTDC1]], S100A8/S100A9, and [[PTH]]rP. Hair provides a shield against UV-induced skin damage and cancer in terrestrial mammals, illuminating another function of [[VDR]] that facilitates healthful aging.
|mesh-terms=* Aging
* Animals
* Calcium
* Cell Nucleus
* Gene Expression Regulation
* Humans
* Keratinocytes
* Mice
* Models, Biological
* Osteopontin
* Phosphates
* Receptors, Calcitriol
* Signal Transduction
* Wnt Proteins
* beta Catenin

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906618
}}
{{medline-entry
|title=A potential link between phosphate and aging--lessons from Klotho-deficient mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20197072
|abstract=Phosphate homeostasis is maintained primarily by a bone-kidney endocrine axis. When phosphate is in excess, fibroblast growth factor-23 ([[FGF23]]) is secreted from bone and acts on kidney to promote phosphate excretion into urine. [[FGF23]] also reduces serum vitamin D levels to suppress phosphate absorption from intestine. Thus, [[FGF23]] functions as a hormone that induces negative phosphate balance. One critical feature of [[FGF23]] is that it requires Klotho, a single-pass transmembrane protein expressed in renal tubules, as an obligate co-receptor to bind and activate cognate FGF receptors. Importantly, defects in either [[FGF23]] or Klotho not only cause phosphate retention but also a premature-aging syndrome in mice, which can be rescued by resolving hyperphosphatemia. In addition, changes in extracellular and intracellular phosphate concentration affect glucose metabolism, insulin sensitivity, and oxidative stress in vivo and in vitro, which potentially affect aging processes. These findings suggest an unexpected link between inorganic phosphate and aging in mammals.
|mesh-terms=* Aging
* Aging, Premature
* Animals
* Bone and Bones
* Fibroblast Growth Factors
* Homeostasis
* Hyperphosphatemia
* Kidney
* Mice
* Oxidative Stress
* Phosphates
* Receptors, Fibroblast Growth Factor
* Risk Factors
* Vitamin D

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862786
}}
{{medline-entry
|title=Role of [[FGF19]] induced [[FGFR4]] activation in the regulation of glucose homeostasis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20157585
|abstract=[[FGF19]], [[FGF21]], and [[FGF23]] form a unique subfamily of fibroblast growth factors. Because they contain intra-molecular disulfide bonds and show reduced affinity toward heparan sulfate located in the extracellular space, it is thought that, in contrast to other FGFs, they function as endocrine hormones. [[FGF23]] and its co-receptor alphaKlotho are involved in the control of aging, but it is not known if the same holds true for [[FGF19]], which can also signal through alphaKlotho. However, considerable evidence supports a role for [[FGF19]] in controlling various aspects of metabolism. We have recently fully characterized [[FGF19]]/FGFR/co-factor interactions and signaling, and in the current manuscript discuss the contribution of the [[FGF19]]/[[FGFR4]] axis to bile acid and glucose regulation.
|mesh-terms=* Animals
* Bile Acids and Salts
* Blood Glucose
* Fibroblast Growth Factors
* Homeostasis
* Humans
* Mice
* Receptor, Fibroblast Growth Factor, Type 4
|keywords=* FGF19
* FGF21
* FGF23
* aging
* diabetes
* fibroblast growth factors
* insulin
* metabolic diseases
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815751
}}
{{medline-entry
|title=The influence of glomerular filtration rate and age on fibroblast growth factor 23 serum levels in pediatric chronic kidney disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20157196
|abstract=Fibroblast growth factor 23 ([[FGF23]]) is a phosphaturic factor and a suppressor of 1alpha-hydroxylase activity in the kidney. Although its importance in chronic kidney disease (CKD) has been demonstrated in adults, there is little information in pediatric patients. The aims of this study were: 1) to determine reference values for [[FGF23]] serum levels according to glomerular filtration rate (GFR) (measured by the reference standard, inulin clearance), gender, and age; and 2) to evaluate the effects of different etiologies and treatments on [[FGF23]] serum levels in a prospective single-center cohort of 227 CKD children (119 boys). Age, body weight, height, and GFR (mean /- sd) values were: 11.3 /- 4.1 yr, 37 /- 16 kg, 140 /- 20 cm, and 98 /- 34 ml/min per 1.73 m(2), respectively. Calcium, phosphate, [[PTH]], 25 hydroxyvitamin D, 1,25 dihydroxyvitamin D, C-terminal [[FGF23]], and intact [[FGF23]] (mean /- sd) levels were: 2.43 /- 0.11 mmol/liter, 1.41 /- 0.22 mmol/liter, 41 /- 23 pg/ml, 24 /- 10 ng/ml, 152 /- 72 pmol/liter, 76 /- 134 relative units/ml, and 44 /- 37 pg/ml, respectively. There was a wide range of [[FGF23]] serum levels, but [[FGF23]] levels increased when GFR decreased. [[FGF23]] serum levels were not modified by gender, but they increased with age. In univariate analysis, corticosteroid therapy seemed to be associated with increased [[FGF23]] serum levels. A multivariate linear regression analysis found a significant impact of GFR, body mass index, and solid organ transplantation on [[FGF23]] serum levels. Age, GFR, body mass index, and solid organ transplantation seem to influence [[FGF23]] serum levels in a pediatric population. The impact of corticosteroids on [[FGF23]] metabolism should be further investigated; further longitudinal studies will also help to better define the prognostic impact of [[FGF23]] serum levels in pediatric CKD in terms of disease progression, cardiovascular morbidities, and bone disabilities.
|mesh-terms=* Adolescent
* Adrenal Cortex Hormones
* Aging
* Body Height
* Body Weight
* Child
* Child, Preschool
* Circadian Rhythm
* Cohort Studies
* Cross-Sectional Studies
* Female
* Fibroblast Growth Factors
* Glomerular Filtration Rate
* Hormones
* Humans
* Inulin
* Kidney Failure, Chronic
* Kidney Transplantation
* Kidney Tubules
* Male
* Prospective Studies
* Reference Values
* Sex Characteristics
* Vitamins
* Water-Electrolyte Balance
* Young Adult

|full-text-url=https://sci-hub.do/10.1210/jc.2009-1576
}}
{{medline-entry
|title=Klotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19730882
|abstract=The klotho gene was identified as an "aging-suppressor" gene in mice that accelerates aging when disrupted and extends life span when overexpressed. It encodes a single-pass transmembrane protein and is expressed primarily in renal tubules. The extracellular domain of Klotho protein is secreted into blood and urine by ectodomain shedding. The two forms of Klotho protein, membrane Klotho and secreted Klotho, exert distinct functions. Membrane Klotho forms a complex with fibroblast growth factor (FGF) receptors and functions as an obligate co-receptor for [[FGF23]], a bone-derived hormone that induces phosphate excretion into urine. Mice lacking Klotho or [[FGF23]] not only exhibit phosphate retention but also display a premature-aging syndrome, revealing an unexpected link between phosphate metabolism and aging. Secreted Klotho functions as a humoral factor that regulates activity of multiple glycoproteins on the cell surface, including ion channels and growth factor receptors such as insulin/insulin-like growth factor-1 receptors. Potential contribution of these multiple activities of Klotho protein to aging processes is discussed.
|mesh-terms=* Aging
* Animals
* Bone and Bones
* Calcium Channels
* Fibroblast Growth Factors
* Glucuronidase
* Homeostasis
* Humans
* Insulin Resistance
* Kidney
* Longevity
* Mice
* Oxidative Stress
* Phosphates
* Receptors, Fibroblast Growth Factor
* TRPV Cation Channels
* Vitamin D

|full-text-url=https://sci-hub.do/10.1007/s00424-009-0722-7
}}
{{medline-entry
|title=[Aspects of mammalian aging from alphaklotho study].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19591273
|abstract=Since the discovery of alphaklotho-mutant mice, it has been questioned whether the responsible gene, alphaklotho, makes any effect on 'intrinsic aging' process. So far we found that alphaKlotho regulates transcellular calcium transport by mediating Na,K-ATPase activity and dominates mineral-regulating hormones such as [[PTH]], vitamin D and [[FGF23]]. A new concept is now emerged that alphaklotho integrates mineral homeostasis. Findings of human cases with mineral disorders revealed impairment of alphaklotho expression as a pathological cause. Mineral metabolic system contributes to health and thus its disruption should result in acceleration of aging and disease.
|mesh-terms=* Aging
* Animals
* Glucuronidase
* Mice
* Mice, Mutant Strains
* Minerals

}}
{{medline-entry
|title=[Fibroblast Growth Factor 23-Klotho: a new axis of phosphate balance control].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19480830
|abstract=The kidney is a key player of phosphate balance, it determines serum phosphate levels by coupling phosphate reabsorption in the renal proximal tubule, calcitriol synthesis and consequently intestinal -phosphate absorption. The identification of fibroblast growth factor 23 ([[FGF23]]) as a hormone regulating phosphate and calcitriol metabolism has unveiled the mechanisms that coordinate these renal proximal tubule functions. A bone-kidney axis has emerged that controls bone mineralization. Animal model studies have improved our understanding of phosphate homeostasis and revealed the role of the Klotho protein, which is mandatory to [[FGF23]] action. In this review, we detail [[FGF23]] and Klotho implication in physiology and in genetic or acquired disorders. Phosphate ion is involved in vascular and soft tissue calcification and is important for cell proliferation. Disorders of [[FGF23]]-klotho axis alter life span and are involved in senescence.
|mesh-terms=* Aging
* Animals
* Calcification, Physiologic
* Calcitriol
* Cell Division
* Fibroblast Growth Factors
* Glucuronidase
* Homeostasis
* Humans
* Hyperphosphatemia
* Hypophosphatemia
* Intestinal Absorption
* Kidney Tubules, Proximal
* Longevity
* Mice
* Mice, Knockout
* Phosphates

|full-text-url=https://sci-hub.do/10.1051/medsci/2009255489
}}
{{medline-entry
|title=[Clinical aspect of recent progress in phosphate metabolism. [[FGF23]]; physiological action and molecular mechanism in the regulation of phosphate and vitamin D metabolism].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19483273
|abstract=Fibroblast growth factor (FGF) 23 is an endocrine hormone regulating the phosphate and vitamin D metabolism in the normal physiology. Recent studies have revealed that Klotho plays an essential role in [[FGF23]] signaling. Klotho-deficient mice exhibit premature aging-like phenotypes, and therefore, this molecule has provided insights into the molecular mechanism of aging. However, it is suggested that the phenotype of the Klotho-deficient mice results from the disturbance in the phosphate and vitamin D metabolism. The importance of the [[FGF23]]/Klotho system thus is evident, but additional questions arose from this new concept.
|mesh-terms=* Aging
* Amino Acid Sequence
* Animals
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Mice
* Molecular Sequence Data
* Phosphates
* Signal Transduction
* Vitamin D

|full-text-url=https://sci-hub.do/CliCa0906794801
}}
{{medline-entry
|title=Vitamin D and aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19444937
|abstract=Recent studies using genetically modified mice, such as [[FGF23]]-/- and Klotho-/- mice that exhibit altered mineral homeostasis due to a high vitamin D activity showed features of premature aging that include retarded growth, osteoporosis, atherosclerosis, ectopic calcification, immunological deficiency, skin and general organ atrophy, hypogonadism and short lifespan. The phenotype reversed by normalizing vitamin D and/or mineral homeostasis. Thus, hypervitaminosis D due to an increased 1alpha-hydroxylase activity seems to be a cause of the premature aging. In several studies, we have described that a complete or partial lack of vitamin D action ([[VDR]]-/- mice and [[CYP27B1]]-/-) show almost similar phenotype as [[FGF23]]-/- or Klotho-/- mice. [[VDR]] mutant mice have growth retardation, osteoporosis, kyphosis, skin thickening and wrinkling, alopecia, ectopic calcification, progressive loss of hearing and balance as well as short lifespan. [[CYP27B1]]-/- mice do not show alopecia nor balance deficit, which might be apo[[VDR]]-dependent or calcidiol-dependent. The features are typical to premature aging. The phenotype is resistant to a normalization of the mineral homeostasis by a rescue diet containing high calcium and phosphate. Taken together, aging shows a U-shaped dependency on hormonal forms of vitamin D suggesting that there is an optimal concentration of vitamin D in delaying aging phenomena. Our recent study shows that calcidiol is an active hormone. Since serum calcidiol but not calcitriol is fluctuating in physiological situations, calcidiol might determine the biological output of vitamin D action. Due to its high serum concentration and better uptake of calcidiol-[[DBP]] by the target cells through the cubilin-megalin system, calcidiol seems to be an important circulating hormone. Therefore, serum calcidiol might be associated with an increased risk of aging-related chronic diseases more directly than calcitriol. Aging and cancer seem to be tightly associated phenomena. Accumulation of damage on DNA and telomeres cause both aging and cancer, moreover the signalling pathways seem to converge on tumour suppressor protein, p53, which seems to be regulated by vitamin D. Also, the insulin-like growth factor signalling pathway (IGF-1, IGFBPs, IGFR) and fibroblast growth factor-23 (FGF-23) regulate growth, aging and cancer. Vitamin D can regulate these signalling pathways, too. Also NF-kappaB and telomerase reverse transcriptase (TERT) might be molecular mechanisms mediating vitamin D action in aging and cancer. Calcidiol serum concentrations show a U-shaped risk of prostate cancer suggesting an optimal serum concentration of 40-60 nmol/L for the lowest cancer risk. Therefore, it is necessary to study several common aging-associated diseases such as osteoporosis, hypertension and diabetes known to be vitamin D-dependent before any recommendations of an optimal serum concentration of calcidiol are given.
|mesh-terms=* Aging
* Aging, Premature
* Animals
* Calcifediol
* Calcitriol
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Neoplasms
* Nutrition Disorders
* Vitamin D
* Vitamin D Deficiency

|full-text-url=https://sci-hub.do/10.1016/j.jsbmb.2008.12.020
}}
{{medline-entry
|title=Therapeutic effects of anti-[[FGF23]] antibodies in hypophosphatemic rickets/osteomalacia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19419316
|abstract=X-linked hypophosphatemia (XLH), characterized by renal phosphate wasting, is the most common cause of vitamin D-resistant rickets. It has been postulated that some phosphaturic factor plays a causative role in XLH and its murine homolog, the Hyp mouse. Fibroblast growth factor 23 ([[FGF23]]) is a physiological phosphaturic factor; its circulatory level is known to be high in most patients with XLH and Hyp mice, suggesting its pathophysiological role in this disease. To test this hypothesis, we treated Hyp mice with anti-[[FGF23]] antibodies to inhibit endogenous [[FGF23]] action. A single injection of the antibodies corrected the hypophosphatemia and inappropriately normal serum 1,25-dihydroxyvitamin D. These effects were accompanied by increased expressions of type IIa sodium-phosphate cotransporter and 25-hydroxyvitamin-D-1alpha-hydroxylase and a suppressed expression of 24-hydroxylase in the kidney. Repeated injections during the growth period ameliorated the rachitic bone phenotypes typically observed in Hyp mice, such as impaired longitudinal elongation, defective mineralization, and abnormal cartilage development. Thus, these results indicate that excess actions of [[FGF23]] underlie hypophosphatemic rickets in Hyp mice and suggest a novel therapeutic potential of the [[FGF23]] antibodies for XLH.
|mesh-terms=* Aging
* Animals
* Antibodies
* Body Weight
* Familial Hypophosphatemic Rickets
* Female
* Fibroblast Growth Factors
* Genetic Diseases, X-Linked
* Growth Plate
* Immunohistochemistry
* Injections, Subcutaneous
* Male
* Mice
* Osteomalacia
* Tibia
* Time Factors
* Vitamin D

|full-text-url=https://sci-hub.do/10.1359/jbmr.090509
}}
{{medline-entry
|title=Klotho and aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19230844
|abstract=The klotho gene encodes a single-pass transmembrane protein that forms a complex with multiple fibroblast growth factor (FGF) receptors and functions as an obligatory co-receptor for [[FGF23]], a bone-derived hormone that induces negative phosphate balance. Defects in either Klotho or Fgf23 gene expression cause not only phosphate retention but also a premature-aging syndrome in mice, unveiling a potential link between phosphate metabolism and aging. In addition, the extracellular domain of Klotho protein is clipped on the cell surface and secreted into blood stream, potentially functioning as an endocrine factor. The secreted Klotho protein has a putative sialidase activity that modifies glycans on the cell surface, which may explain the ability of secreted Klotho protein to regulate activity of multiple ion channels and growth factors including insulin, IGF-1, and Wnt. Secreted Klotho protein also protects cells and tissues from oxidative stress through a mechanism yet to be identified. Thus, the transmembrane and secreted forms of Klotho protein have distinct functions, which may collectively affect aging processes in mammals.
|mesh-terms=* Aging
* Animals
* Calcium Channels
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Mice
* Models, Biological
* Mutation
* Vitamin D

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743784
}}
{{medline-entry
|title=Vitamin D receptor genotype in hypophosphatemic rickets as a predictor of growth and response to treatment.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18827005
|abstract=Treatment of X-linked hypophosphatemic rickets improves bone mineralization and bone deformities, but its effect on skeletal growth is highly variable. Genetic variants in the promoter region of the vitamin D receptor ([[VDR]]) gene may explain the response to treatment because this receptor mediates vitamin D action. We studied the [[VDR]] promoter haplotype structure in a large cohort of 91 patients with hypophosphatemic rickets including 62 patients receiving 1alpha-hydroxyvitamin D3 derivatives and phosphates from early childhood on. Treatment improved bone deformities and final height, but 39% of treated patients still had short stature at the end of growth (-2 sd score or below). Height was closely associated with [[VDR]] promoter Hap1 genotype. Hap1(-) patients (35% of the cohort) had severe growth defects. This disadvantageous association of Hap1(-) status with height was visible before treatment, under treatment, and on to adulthood. Gender and age at initiation of treatment could not account for the Hap1 effect. No association with growth was found with a polymorphism of the [[PTH]] receptor gene otherwise found to be associated with adult height. Compared with Hap1( ) patients, those who were Hap1(-) had a higher urinary calcium response to 1alpha-hydroxyvitamin D3 and had significantly lower circulating [[FGF23]] levels (C-terminal assay), taking into account their phosphate and 1alpha-hydroxyvitamin D3 intakes. The present work identifies the [[VDR]] promoter genotype as a key predictor of growth under treatment with 1alpha-hydroxyvitamin D3 derivatives in patients with hypophosphatemic rickets, including those with established [[PHEX]] alterations. The [[VDR]] promoter genotype appears to provide valuable information for adjusting treatment and for deciding upon the utility of early GH therapy.
|mesh-terms=* Adolescent
* Adult
* Aging
* Calcitriol
* Child
* Child, Preschool
* Cohort Studies
* DNA
* Familial Hypophosphatemic Rickets
* Female
* Fibroblast Growth Factors
* Genetic Diseases, X-Linked
* Genotype
* Haplotypes
* Humans
* Male
* Middle Aged
* Organophosphates
* Predictive Value of Tests
* Promoter Regions, Genetic
* Receptor, Parathyroid Hormone, Type 1
* Receptors, Calcitriol
* Reverse Transcriptase Polymerase Chain Reaction
* Sex Characteristics
* Young Adult

|full-text-url=https://sci-hub.do/10.1210/jc.2007-2553
}}
{{medline-entry
|title=[Role of kidney in calcium homeostasis and premature aging].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18591745
|abstract=The kidney plays a critical role in the calcium (Ca) homeostasis. With advancing age, the kidney function, including glomerular filtration rate and tubular electrolyte reabsorption, is deteriorating without any kidney disease. Disturbed Ca metabolism may be associated with premature aging process, in which various cellular function is impaired by intracellular Ca burden due to increased Ca efflux from bone. Fibroblast growth factor (FGF) 23, a novel phosphate (P) -regulating factor, is involved in disorders of mineral bone metabolism. Recent studies suggest that [[FGF23]] plays a certain role in premature aging process through altered P and vitamin D metabolism.
|mesh-terms=* Aging
* Animals
* Bone and Bones
* Calcium
* Fibroblast Growth Factors
* Homeostasis
* Humans
* Kidney
* Phosphorus
* Vitamin D

|full-text-url=https://sci-hub.do/CliCa0807942946
}}
{{medline-entry
|title=Klotho as a regulator of oxidative stress and senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18177265
|abstract=The klotho gene functions as an aging-suppressor gene that extends life span when overexpressed and accelerates aging-like phenotypes when disrupted in mice. The klotho gene encodes a single-pass transmembrane protein that binds to multiple fibroblast growth factor (FGF) receptors and functions as a co-receptor for [[FGF23]], a bone-derived hormone that suppresses phosphate reabsorption and vitamin D biosynthesis in the kidney. In addition, the extracellular domain of Klotho protein is shed and secreted, potentially functioning as a humoral factor. The secreted Klotho protein can regulate multiple growth factor signaling pathways, including insulin/IGF-1 and Wnt, and the activity of multiple ion channels. Klotho protein also protects cells and tissues from oxidative stress, yet the precise mechanism underlying these activities remains to be determined. Thus, understanding of Klotho protein function is expected to provide new insights into the molecular basis for aging, phosphate/vitamin D metabolism, cancer and stem cell biology.
|mesh-terms=* Aging
* Animals
* Atrophy
* Bone Density
* Calcinosis
* Cognition Disorders
* Female
* Fibroblast Growth Factors
* Glucuronidase
* Hearing Loss
* Hypogonadism
* Insulin
* Insulin-Like Growth Factor I
* Ion Channels
* Male
* Mice
* Mice, Transgenic
* Nitric Oxide
* Osteoporosis
* Oxidative Stress
* Pulmonary Emphysema
* Signal Transduction
* Skin
* Spinal Cord Diseases
* Wnt Proteins

|full-text-url=https://sci-hub.do/10.1515/BC.2008.028
}}
{{medline-entry
|title=Klotho: an antiaging protein involved in mineral and vitamin D metabolism.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17332731
|abstract=Klotho gene mutation leads to a syndrome strangely resembling chronic kidney disease patients undergoing dialysis with multiple accelerated age-related disorders, including hypoactivity, sterility, skin thinning, muscle atrophy, osteoporosis, vascular calcifications, soft-tissue calcifications, defective hearing, thymus atrophy, pulmonary emphysema, ataxia, and abnormalities of the pituitary gland, as well as hypoglycemia, hyperphosphatemia, and paradoxically high-plasma calcitriol levels. Conversely, mice overexpressing klotho show an extended existence and a slow aging process through a mechanism that may involve the induction of a state of insulin and oxidant stress resistance. Two molecules are produced by the klotho gene, a membrane bound form and a circulating form. However, their precise biological roles and molecular functions have been only partly deciphered. Klotho can act as a circulating factor or hormone, which binds to a not yet identified high-affinity receptor and inhibits the intracellular insulin/insulin-like growth factor-1 (IGF-1) signaling cascade; klotho can function as a novel beta-glucuronidase, which deglycosylates steroid beta-glucuronides and the calcium channel transient receptor potential vallinoid-5 (TRPV5); as a cofactor essential for the stimulation of fibroblast growth factor (FGF) receptor by [[FGF23]]. The two last functions have propelled klotho to the group of key factors regulating mineral and vitamin D metabolism, and have also stimulated the interest of the nephrology community. The purpose of this review is to provide a nephrology-oriented overview of klotho and its potential implications in normal and altered renal function states.
|mesh-terms=* Aging
* Animals
* Bone and Bones
* Glucuronidase
* Humans
* Kidney
* Minerals
* RNA, Messenger
* Vitamin D

|full-text-url=https://sci-hub.do/10.1038/sj.ki.5002163
}}
{{medline-entry
|title=[Vitamin D and phosphate metabolism; relationship with aging-regulating gene].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16816473
|abstract=It has been known that phosphate homeostasis is mainly regulated by parathyroid hormone and vitamin D. Fibroblast growth factor 23 ([[FGF23]]) has been identified as a novel factor that regulates vitamin D and phosphate metabolism. Genetic defect of [[FGF23]] in mice revealed not only abnormal vitamin D and phosphate metabolism, but also premature aging-like phenotype that is quite similar to Klotho mice. Regulation of vitamin D and phosphate metabolism is closely related to aging processes as well as bone and mineral metabolism.
|mesh-terms=* Aging
* Aging, Premature
* Animals
* Bone and Bones
* Fibroblast Growth Factors
* Forkhead Transcription Factors
* Glucuronidase
* Humans
* Insulin-Like Growth Factor I
* Mice
* Phosphates
* Phosphorus, Dietary
* Signal Transduction
* Vitamin D

|full-text-url=https://sci-hub.do/CliCa060711371142
}}
{{medline-entry
|title=Toward a better understanding of Klotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16672727
|abstract=klotho mutant mice were originally described as a short-lived mouse model with premature aging-like disorders. The klotho gene responsible for these phenotypes encodes a type I membrane protein with a considerable similarity to beta-glycosidase. klotho is predominantly expressed in tissues functioning in the regulation of calcium homeostasis. Suggested functions of Klotho are (i) a fundamental regulator of calcium homeostasis, namely, a cofactor for the fibroblast growth factor (FGF) receptor 1c in [[FGF23]] signaling and a regulator of parathyroid hormone secretion; (ii) a hormone that interferes with the intracellular signaling of insulin and insulin-like growth factor-1; and (iii) a beta-glucuronidase that activates the transient receptor potential ion channel [[TRPV5]] by trimming its sugar moiety. How can we reconcile these pleiotropic functions of Klotho? Is there any common mechanism? Further in vivo studies, and biochemical as well as physiological analyses, are required for a better understanding of the molecular aspects of Klotho.
|mesh-terms=* Aging
* Aging, Premature
* Animals
* Calcium
* Fibroblast Growth Factors
* Glucuronidase
* Homeostasis
* Insulin Antagonists
* Mice
* Mutation
* Phenotype
* Signal Transduction

|full-text-url=https://sci-hub.do/10.1126/sageke.2006.8.pe11
}}
{{medline-entry
|title=Loss of renal phosphate wasting in a child with autosomal dominant hypophosphatemic rickets caused by a [[FGF23]] mutation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11805436
|abstract=A girl with autosomal dominant hypophosphatemic rickets, presented with clinical, radiological and laboratory signs of rickets at the age of 11 months. She showed a good response to the treatment with low doses of oral phosphate and calcitriol. Surprisingly, she lost her renal phosphate wasting at the age of 8 years, indicating that the disturbed phosphate metabolism can be compensated by hormonal or other factors.
|mesh-terms=* Administration, Oral
* Aging
* Calcitriol
* Calcium Channel Agonists
* Child
* Female
* Fibroblast Growth Factors
* Genes, Dominant
* Humans
* Hypophosphatemia, Familial
* Kidney
* Mutation
* Pedigree
* Phosphates

|full-text-url=https://sci-hub.do/10.1159/000050018
}}

FGF21

2021-05-12T15:36:45Z

OdysseusBot: Новая страница: «Fibroblast growth factor 21 precursor (FGF-21) [UNQ3115/PRO10196] ==Publications== {{medline-entry |title=Differential effects of sulfur amino acid-restricted a...»

Fibroblast growth factor 21 precursor (FGF-21) [UNQ3115/PRO10196]

==Publications==

{{medline-entry
|title=Differential effects of sulfur amino acid-restricted and low-calorie diets on gut microbiome profile and bile acid composition in male C57BL6/J mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33106871
|abstract=Diet can affect health and longevity by altering the gut microbiome profile. Sulfur amino acid restriction (SAAR), like caloric restriction, extends lifespan. But, its effect on the gut microbiome profile and functional significance of such effects are understudied. We investigated whether SAAR alters the gut microbiome profile and bile acid composition, an index of microbial metabolism. We also compared these changes with those induced by a 12% low-calorie diet (LCD). Male 21-week-old C57BL6/J mice were fed CD (0.86% methionine), SAAR (0.12% methionine), and LCD diets (0.86% methionine). After ten weeks on the diet, plasma markers and fecal microbial profiles were determined. SAAR mice had lower body weights and IGF-1, and higher food intake and [[FGF21]] than CD mice. Compared to SAAR mice, LCD mice had higher body weights, lower FGF-21 and food intake, but similar IGF-1. β-Diversity indices were different between SAAR and LCD, LCD and CD, but not between CD and SAAR. In group-wise comparisons of individual taxa, differences were more discernable between SAAR and LCD than between other groups. Abundances of firmicutes, clostridiaceae, and turicibacteraceae were higher, but verrucomicrobia was lower in SAAR than in LCD. Secondary bile acids and the ratio of secondary to primary bile acids were lower in SAAR than in LCD. SAAR favored bile acid conjugation with glycine at the expense of taurine. Overall, SAAR and LCD diets induced distinct changes in the gut microbiome and bile acid profiles. Additional studies on the role of these changes in improving health and lifespan are warranted.

|keywords=* Clostridales
* firmicutes
* lifespan
* methionine restriction
* sulfur metabolism
|full-text-url=https://sci-hub.do/10.1093/gerona/glaa270
}}
{{medline-entry
|title=Disease-specific plasma levels of mitokines [[FGF21]], [[GDF15]], and Humanin in type II diabetes and Alzheimer's disease in comparison with healthy aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33131010
|abstract=Fibroblast Growth Factor 21 ([[FGF21]]), Growth Differentiation Factor 15 ([[GDF15]]), and Humanin (HN) are mitochondrial stress-related mitokines, whose role in health and disease is still debated. In this study, we confirmed that their plasma levels are positively correlated with age in healthy subjects. However, when looking at patients with type 2 diabetes (T2D) or Alzheimer's disease (AD), two age-related diseases sharing a mitochondrial impairment, we found that [[GDF15]] is elevated in T2D but not in AD and represents a risk factor for T2D complications, while [[FGF21]] and HN are lower in AD but not in T2D. Moreover, [[FGF21]] reaches the highest levels in centenarian' offspring, a model of successful aging. As a whole, these data indicate that (i) the adaptive mitokine response observed in healthy aging is lost in age-related diseases, (ii) a common expression pattern of mitokines does not emerge in T2D and AD, suggesting an unpredicted complexity and disease-specificity, and (iii) [[FGF21]] emerges as a candidate marker of healthy aging.

|keywords=* AD
* Aging
* FGF21
* GDF15
* Humanin
* T2D
|full-text-url=https://sci-hub.do/10.1007/s11357-020-00287-w
}}
{{medline-entry
|title=Alignment of Alzheimer's disease amyloid β-peptide and klotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32999998
|abstract=The cause of Alzheimer's disease (AD) is poorly understood. In 1991, the amyloid hypothesis postulated that β-amyloid (Aβ) accumulation is a key element. It follows that clearing the brain of Aβ would be beneficial, which has not been the case. Therefore, Aβ is likely a result, not a cause, of AD and may be protective rather than harmful. The apolipoprotein E4 (apoE4) allele is the strongest genetic risk factor for AD. Klotho ([[KL]]), encoded by the [[KL]] gene, may be another AD-related protein. [[FGF21]] is a circulating endocrine hormone, mainly secreted by the liver, mostly during fasting. [[FGF21]] acts by binding to its receptor [[FGFR1]] and co-receptor β-klotho. [[FGF21]] is neuroprotective and could delay onset of AD. In the present study, the [[KL]] protein structure was examined to determine whether it may interact with Aβ. Protein data bank (pdb) entries for klotho and Aβ were searched on the RCSB Protein Data Bank for β-[[KL]] and AD amyloid β-peptide. The protein structures were superimposed and aligned on PYMOL v2.3.4 with the super command, which super aligns two protein selections. To evaluate the conservation and alignment of the Aβ and [[KL]] genomes across species, BLAT, the Blast-Like Alignment Tool of the UCSC Genome Browser, was used. The amino acid residues phe76-val96 of [[KL]] aligned closely with residues asp7-asn27 of Aβ. Cross-species comparison of [[KL]] revealed a high degree of alignment and conservation in the chimp and 27 other primates; however, less alignment and conservation were observed in the mouse, dog and elephant, even less in the chicken, western clawed frog ([i]Xenopus tropicalis[/i]), zebrafish and lamprey. The current finding of amino acid residues phe76-val96 of klotho aligning closely with residues asp7-asn27 of Aβ suggests that Aβ can enhance the ability of klotho to draw [[FGF21]] to regions of incipient neurodegeneration in AD. The problem arises with age. Older individuals do not heal or repair tissue damage as well as younger individuals. As neurodegeneration advances in an older individual, perhaps caused by neuroinflammation related to herpes simplex virus type 1, increasing amounts of amyloid are produced, forming an adhesive web, as the brain tries to hold the pathologic process in check. Meanwhile, the damage increases and spreads. Progressive neurodegeneration and cognitive decline are the outcome.

|keywords=* Alzheimer’s disease
* HSV-1
* aging
* alignment
* klotho
* neurodegeneration
* neuroinflammation
* protein
* ubiquitin
* β-amyloid
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521834
}}
{{medline-entry
|title=Relationship between physical activity and circulating fibroblast growth factor 21 in middle-aged and older adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32911033
|abstract=Circulating levels of fibroblast growth factor 21 ([[FGF21]]) increase with advancing age and may lead to the development of cardiometabolic diseases via impaired lipid and glucose metabolism. While physical activity can reduce these risks of cardiometabolic dysfunction, it remains obscure whether circulation [[FGF21]] levels are influenced by physical activity. The purpose of this study was to investigate the relations between daily physical activities and circulating [[FGF21]] levels in middle-aged and older adults. In this cross-sectional study with 110 middle-aged and 102 older adults, circulating (serum) [[FGF21]] levels were evaluated by enzyme-linked immunosorbent assay, and the time spent in light-intensity physical activity (LPA) and moderate-to-vigorous-intensity physical activity (MVPA) was assessed using a uniaxial accelerometer. Serum [[FGF21]] levels in the older group (158 pg/mL) were significantly higher than those in the middle-aged group (117 pg/mL). When we examined the joint association of age (middle-aged or older) and MVPA (lower or higher than the median) groups, serum [[FGF21]] levels in the older and higher MVPA group (116 pg/mL) were significantly lower than those in the older and lower MVPA group (176 pg/mL). However, there was no difference in serum [[FGF21]] levels between the lower and higher MVPA groups in the middle-aged group. In multivariable liner regression analysis, serum [[FGF21]] levels were independently determined by MVPA time after adjusting for potential covariates in older adults (β = -0.209). These cross-sectional study findings indicate that the time spent in MVPA is an independent determinant of circulating [[FGF21]] levels, and that an age-related increase in serum [[FGF21]] levels may be attenuated by habitually performing MVPA. (250/250 words).

|keywords=* Accelerometer
* Activity intensity
* Aging
* FGF21
* Physical activity
|full-text-url=https://sci-hub.do/10.1016/j.exger.2020.111081
}}
{{medline-entry
|title=Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32863214
|abstract=Exercise and dietary intervention are currently available strategies to treat nonalcoholic fatty liver disease (NAFLD), while the underlying mechanism remains controversial. Emerging evidence shows that lipophagy is involved in the inhibition of the lipid droplets accumulation. However, it is still unclear if exercise and dietary intervention improve NAFLD through regulating lipophagy, and how exercise of skeletal muscle can modulate lipid metabolism in liver. Moreover, NAFLD is associated with aging, and little is known about the effect of lipid accumulation on aging process. Here in vivo and in vitro models, we found that exercise and dietary intervention reduced lipid droplets formation, decreased hepatic triglyceride in the liver induced by high-fat diet. Exercise and dietary intervention enhanced the lipophagy by activating AMPK/ULK1 and inhibiting Akt/mTOR/ULK1 pathways respectively. Furthermore, exercise stimulated [[FGF21]] production in the muscle, followed by secretion to the circulation to promote the lipophagy in the liver via an AMPK-dependent pathway. Importantly, for the first time, we demonstrated that lipid accumulation exacerbated liver aging, which was ameliorated by exercise and dietary intervention through inducing lipophagy. Our findings suggested a new mechanism of exercise and dietary intervention to improve NAFLD through promoting lipophagy. The study also provided evidence to support that muscle exercise is beneficial to other metabolic organs such as liver. The [[FGF21]]-mediated AMPK dependent lipophagy might be a potential drug target for NAFLD and aging caused by lipid metabolic dysfunction.

|keywords=* Aging
* Exercise
* FGF21
* Lipophagy
* Nonalcoholic fatty liver disease (NAFLD)
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365984
}}
{{medline-entry
|title=Mitochondria, immunosenescence and inflammaging: a role for mitokines?
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32757036
|abstract=A global reshaping of the immune responses occurs with ageing, indicated as immunosenescence, where mitochondria and mitochondrial metabolism play an important role. However, much less is known about the role of mitochondrial stress response in this reshaping and in particular of the molecules induced by such response, collectively indicated as mitokines. In this review, we summarize the current knowledge on the role of mitokines in modulating immune response and inflammation focusing on [[GDF15]], [[FGF21]] and humanin and their possible involvement in the chronic age-related low-grade inflammation dubbed inflammaging. Although many aspects of their biology are still controversial, available data suggest that these mitokines have an anti-inflammatory role and increase with age. Therefore, we hypothesize that they can be considered part of an adaptive and integrated immune-metabolic mechanism activated by mitochondrial dysfunction that acts within the framework of a larger anti-inflammatory network aimed at controlling both acute inflammation and inflammaging.

|keywords=* Human ageing
* Immunosenescence
* Inflammaging
* Mitochondrial metabolism
* Mitokines
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666292
}}
{{medline-entry
|title=Age-at-onset-dependent effects of sulfur amino acid restriction on markers of growth and stress in male F344 rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32573078
|abstract=Trade-offs in life-history traits are clinically and mechanistically important. Sulfur amino acid restriction (SAAR) extends lifespan. But whether this benefit comes at the cost of other traits including stress resistance and growth is unclear. We investigated the effects of SAAR on growth markers (body weight, [[IGF1]], and IGFBP3) and physiological stresses. Male-F344 rats were fed control (0.86% Met) and SAAR (0.17% Met) diets starting at 2, 10, and 20 months. Rats were injected with keyhole-limpet-hemocyanin (KLH) to measure immune responses (anti-KLH-IgM, anti-KLH-IgG, and delayed-type-hypersensitivity [DTH]). Markers of ER stress ([[FGF21]] and adiponectin), detoxification capacity (glutathione [GSH] concentrations, GSH-S-transferase [GST], and cytochrome-P -reductase [CPR] activities), and low-grade inflammation (C-reactive protein [CRP]) were also determined. SAAR decreased body weight, liver weight, food intake, plasma [[IGF1]], and IGFBP3; the effect size diminished with increasing age-at-onset. SAAR increased [[FGF21]] and adiponectin, but stress damage markers GRP78 and Xbp1 were unchanged, suggesting that ER stress is hormetic. SAAR increased hepatic GST activity despite lower GSH, but CPR activity was unchanged, indicative of enhanced detoxification capacity. Other stress markers were either uncompromised (CRP, anti-KLH-IgM, and DTH) or slightly lower (anti-KLH-IgG). Increases in stress markers were similar across all ages-at-onset, except for adiponectin, which peaked at 2 months. Overall, SAAR did not compromise stress responses and resulted in maximal benefits with young-onset. In survival studies, median lifespan extension with initiation at 52 weeks was 7 weeks (p = .05); less than the 33.5-week extension observed in our previous study with 7-week initiation. Findings support SAAR translational studies and the need to optimize Met dose based on age-at-onset.

|keywords=* ER stress
* cysteine
* glutathione
* hormesis
* lifespan
* methionine
* trade-offs
* translational
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426777
}}
{{medline-entry
|title=Fibroblast growth factor 21 prolongs lifespan and improves stress tolerance in the silkworm, [i]Bombyx mori[/i].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32309367
|abstract=Fibroblast growth factor 21 ([[FGF21]]), an FGF family member, is an atypical hormone and pro-longevity factor. To better understand of the effects of exogenous administration of [[FGF21]] on lifespan and stress tolerance, and the underlying molecular basis, we used the silkworm, [i]Bombyx mori[/i], as an experimental animal model to evaluate [[FGF21]]'s pharmaceutical effects. Lifespan was significantly prolonged in female silkworms with [[FGF21]] replenishment, whereas no effect was observed in the male silkworms. [[FGF21]] replenishment also significantly improved the activity of antioxidant systems such as glutathione-S-transferase (GST) and superoxide dismutase (SOD) and significantly decreased malondialdehyde (MDA) content. Moreover, [[FGF21]] was found to play a critical role in enhancing stress resistance, including ultraviolet (UV) irradiation tolerance and thermotolerance. Furthermore, [i]AMPK[/i], [i]FoxO[/i], and sirtuins were activated by [[FGF21]] and may be responsible for the prolonged lifespan and enhanced antioxidant activity observed in silkworms. Collectively, the results suggest the molecular pathways underlying of [[FGF21]]-induced longevity and stress tolerance, and support the use of silkworms as a promising experimental animal model for evaluating the pharmaceutical effects of small molecules.

|keywords=* Bombyx mori
* fibroblast growth factor 21 (FGF21)
* lifespan
* oxidation resistance
* stress tolerance
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154471
}}
{{medline-entry
|title=Myokines as biomarkers of frailty and cardiovascular disease risk in females.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32017952
|abstract=Frailty is a risk factor for cardiovascular disease (CVD). Biomarkers have the potential to detect the early stages of frailty, such as pre-frailty. Myokines may act as biomarkers of frailty-related disease progression, as a decline in muscle health is a hallmark of the frailty phenotype. This study is a secondary analysis of 104 females 55 years of age or older with no previous history of CVD. Differences in systemic myokine concentrations based on frailty status and CVD risk profile were examined using a case-control design. Propensity matching identified two sets of 26 pairs with pre-frailty as the exposure variable in low or elevated CVD risk groups for a total 104 female participants. Frailty was assessed using the Fried Criteria (FC) and CVD risk was assessed using the Framingham Risk Score (FRS). Factorial ANOVA compared the main effects of frailty, CVD risk, and their interaction on the concentrations of 15 myokines. Differences were found when comparing elevated CVD risk status with low for the concentrations of [[EPO]] (384.76 ± 1046.07 vs. 206.63 ± 284.61 pg/mL, p = .001), [[FABP3]] (2772.61 ± 3297.86 vs. 1693.31 ± 1019.34 pg/mL, p = .017), [[FGF21]] (193.17 ± 521.09 vs. 70.18 ± 139.51 pg/mL, p = .010), IL-6 (1.73 ± 4.97 vs. 0.52 ± 0.89 pg/mL, p = .023), and IL-15 (2.62 ± 10.56 vs. 0.92 ± 1.25 pg/mL, p = .022). Pre-frail females had lower concentrations of fractalkine compared to robust (27.04 ± 20.60 vs. 103.62 ± 315.45 pg/mL, p = .004). Interaction effects between frailty status and CVD risk for [[FGF21]] and [[OSM]] were identified. In elevated CVD risk, pre-frail females, concentrations of [[FGF21]] and [[OSM]] were lower than that of elevated CVD risk, robust females (69.10 ± 62.86 vs. 317.24 ± 719.69, p = .011; 1.73 ± 2.32 vs. 24.43 ± 69.21, p = .018, respectively). These data identified specific biomarkers of CVD risk and biomarkers of frailty that are exacerbated with CVD risk.

|keywords=* Aging
* Biomarkers
* Cardiovascular disease
* Females
* Frailty
* Myokines
|full-text-url=https://sci-hub.do/10.1016/j.exger.2020.110859
}}
{{medline-entry
|title=Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31723038
|abstract=The gut microbiota evolves as the host ages, yet the effects of these microbial changes on host physiology and energy homeostasis are poorly understood. To investigate these potential effects, we transplanted the gut microbiota of old or young mice into young germ-free recipient mice. Both groups showed similar weight gain and skeletal muscle mass, but germ-free mice receiving a gut microbiota transplant from old donor mice unexpectedly showed increased neurogenesis in the hippocampus of the brain and increased intestinal growth. Metagenomic analysis revealed age-sensitive enrichment in butyrate-producing microbes in young germ-free mice transplanted with the gut microbiota of old donor mice. The higher concentration of gut microbiota-derived butyrate in these young transplanted mice was associated with an increase in the pleiotropic and prolongevity hormone fibroblast growth factor 21 ([[FGF21]]). An increase in [[FGF21]] correlated with increased AMPK and SIRT-1 activation and reduced mTOR signaling. Young germ-free mice treated with exogenous sodium butyrate recapitulated the prolongevity phenotype observed in young germ-free mice receiving a gut microbiota transplant from old donor mice. These results suggest that gut microbiota transplants from aged hosts conferred beneficial effects in responsive young recipients.
|mesh-terms=* Animals
* Butyrates
* Fecal Microbiota Transplantation
* Fibroblast Growth Factors
* Gastrointestinal Microbiome
* Germ-Free Life
* Hippocampus
* Intestines
* Liver
* Longevity
* Male
* Metabolome
* Mice, Inbred C57BL
* Microtubule-Associated Proteins
* Neurogenesis
* Neurons
* Neuropeptides
* Phenotype
* Proton Magnetic Resonance Spectroscopy

|full-text-url=https://sci-hub.do/10.1126/scitranslmed.aau4760
}}
{{medline-entry
|title=Fibroblast Growth Factor 21 Mediates the Associations between Exercise, Aging, and Glucose Regulation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31490857
|abstract=Aging increases the prevalence of glucose intolerance, but exercise improves glucose homeostasis. The fibroblast growth factor 21 ([[FGF21]])-adiponectin axis helps regulate glucose metabolism. However, the role of [[FGF21]] in mediating glucose metabolism with aging and exercise remains unknown. This study examined whether [[FGF21]] responses to a glucose challenge are associated with habitual exercise, aging and glucose regulation. Eighty age- and sex-matched healthy individuals were assigned to young sedentary and active (≤36 yr, n = 20 each group) and older sedentary and active (≥45 yr, n = 20 each group) groups. Fasted and postprandial blood glucose concentration and plasma concentration of insulin, [[FGF21]], and adiponectin were determined during an oral glucose tolerance test (OGTT). During the OGTT, glucose concentrations were 9% higher (P = 0.008) and [[FGF21]] concentrations were 58% higher (P = 0.014) in the older than the younger group, independent of activity status. Active participants had 40% lower insulin concentration and 53% lower [[FGF21]] concentration than sedentary participants, independent of age (all P < 0.001). Adiponectin concentration during the OGTT did not differ by age (P = 0.448) or activity status (P = 0.611). Within the younger group, postprandial glucose, insulin and [[FGF21]] concentrations during the OGTT were lower in active than in sedentary participants. In the older group, only postprandial insulin and [[FGF21]] concentrations were lower in active participants. [[FGF21]], but not adiponectin, response during the OGTT is higher in older than younger adults and lower in active than sedentary individuals. Exercise-associated reduction in OGTT glucose concentrations was observed in younger but not older adults.
|mesh-terms=* Adiponectin
* Adult
* Aging
* Blood Glucose
* Blood Pressure
* Body Mass Index
* Diabetes Mellitus, Type 2
* Exercise
* Female
* Fibroblast Growth Factors
* Glucose Tolerance Test
* Humans
* Insulin
* Lipids
* Male
* Middle Aged
* Risk Factors

|full-text-url=https://sci-hub.do/10.1249/MSS.0000000000002150
}}
{{medline-entry
|title=Effects of Moderate Chronic Food Restriction on the Development of Postprandial Dyslipidemia with Ageing.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31405194
|abstract=Ageing is a major risk factor for the development of metabolic disorders linked to dyslipidemia, usually accompanied by increased adiposity. The goal of this work was to investigate whether avoiding an excessive increase in adiposity with ageing, via moderate chronic food restriction (FR), ameliorates postprandial dyslipidemia in a rat model of metabolic syndrome associated with ageing. Accordingly, we performed an oral lipid loading test (OLLT) in mature middle-aged (7 months) and middle-old-aged (24 months) Wistar rats fed ad libitum (AL) or under moderate FR for 3 months. Briefly, overnight fasted rats were orally administered a bolus of extra-virgin olive oil (1 mL/Kg of body weight) and blood samples were taken from the tail vein before fat load (t = 0) and 30, 60, 90, 120, 180, and 240 min after fat administration. Changes in serum lipids, glucose, insulin, and glucagon levels were measured at different time-points. Expression of liver and adipose tissue metabolic genes were also determined before (t = 0) and after the fat load (t = 240 min). Postprandial dyslipidemia progressively increased with ageing and this could be associated with hepatic ChREBP activity. Interestingly, moderate chronic FR reduced adiposity and avoided excessive postprandial hypertriglyceridemia in 7- and 24-month-old Wistar rats, strengthening the association between postprandial triglyceride levels and adiposity. The 24-month-old rats needed more insulin to maintain postprandial normoglycemia; nevertheless, hyperglycemia occurred at 240 min after fat administration. FR did not alter the fasted serum glucose levels but it markedly decreased glucagon excursion during the OLLT and the postprandial rise of glycemia in the 24-month-old rats, and [[FGF21]] in the 7-month-old Wistar rats. Hence, our results pointed to an important role of FR in postprandial energy metabolism and insulin resistance in ageing. Lastly, our data support the idea that the vWAT might function as an ectopic site for fat deposition in 7-month-old and in 24-month-old Wistar rats that could increase their browning capacity in response to an acute fat load.
|mesh-terms=* Adiposity
* Aging
* Animals
* Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
* Blood Glucose
* Diet, Fat-Restricted
* Dietary Fats
* Disease Models, Animal
* Dyslipidemias
* Glucagon
* Insulin
* Lipids
* Liver
* Metabolic Syndrome
* Postprandial Period
* Rats
* Rats, Wistar
* Triglycerides
|keywords=* ChREBP
* adipose tissue
* ageing
* oral lipid loading test
* postprandial hypertrigliceridemia
* postprandial thermogenesis
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723802
}}
{{medline-entry
|title=Inhibition of the Fission Machinery Mitigates [[OPA1]] Impairment in Adult Skeletal Muscles.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31208084
|abstract=The maintenance of muscle mass and its ability to function relies on a bioenergetic efficient mitochondrial network. This network is highly impacted by fusion and fission events. We have recently shown that the acute deletion of the fusion protein Opa1 induces muscle atrophy, systemic inflammatory response, precocious epithelial senescence, and premature death that are caused by muscle-dependent secretion of [[FGF21]]. However, both fusion and fission machinery are suppressed in aging sarcopenia, cancer cachexia, and chemotherapy-induced muscle wasting. We generated inducible muscle-specific Opa1 and Drp1 double-knockout mice to address the physiological relevance of the concomitant impairment of fusion and fission machinery in skeletal muscle. Here we show that acute ablation of Opa1 and Drp1 in adult muscle causes the accumulation of abnormal and dysfunctional mitochondria, as well as the inhibition of autophagy and mitophagy pathways. This ultimately results in ER stress, muscle loss, and the reduction of force generation. However, the simultaneous inhibition of the fission protein Drp1 when Opa1 is absent alleviates [[FGF21]] induction, oxidative stress, denervation, and inflammation rescuing the lethal phenotype of Opa1 knockout mice, despite the presence of any muscle weakness. Thus, the simultaneous inhibition of fusion and fission processes mitigates the detrimental effects of unbalanced mitochondrial fusion and prevents the secretion of pro-senescence factors.
|mesh-terms=* Aging
* Animals
* Autophagy
* Dynamins
* Endoplasmic Reticulum Stress
* Fibroblast Growth Factors
* GTP Phosphohydrolases
* Mice, Knockout
* Mitochondria
* Mitochondrial Dynamics
* Mitophagy
* Muscle Weakness
* Muscle, Skeletal
* Muscular Atrophy
* Oxidative Stress
* Proteasome Endopeptidase Complex
* Proteolysis
* Ubiquitin
|keywords=* FGF21
* fission
* mitochondrial fusion
* mitophagy
* muscle dystrophy
* muscle wasting
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627087
}}
{{medline-entry
|title=Higher serum levels of fibroblast growth factor 21 in old patients with cachexia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30933730
|abstract=Fibroblast growth factor (FGF)21 is promptly induced by short fasting in animal models to regulate glucose and fat metabolism. Data on [[FGF21]] in humans are inconsistent and [[FGF21]] has not yet been investigated in old patients with cachexia, a complex syndrome characterized by inflammation and weight loss. The aim of this study was to explore the association of [[FGF21]] with cachexia in old patients compared with their healthy counterparts. Serum [[FGF21]] and its inactivating enzyme fibroblast activation protein ([[FAP]])-α were measured with enzyme-linked immunoassays. Cachexia was defined as ≥5% weight loss in the previous 3 mo and concurrent anorexia (Council on Nutrition appetite questionnaire). We included 103 patients with and without cachexia (76.9 ± 5.2 y of age) and 56 healthy controls (72.9 ± 5.9 y of age). Cachexia was present in 16.5% of patients. These patients had significantly higher total [[FGF21]] levels than controls (952.1 ± 821.3 versus 525.2 ± 560.3 pg/mL; P = 0.012) and the lowest [[FGF21]] levels (293.3 ± 150.9 pg/mL) were found in the control group (global P < 0.001). Although [[FAP]]-α did not differ between the three groups (global P = 0.082), bioactive [[FGF21]] was significantly higher in patients with cachexia (global P = 0.002). Risk factor-adjusted regression analyses revealed a significant association between cachexia and total (β = 649.745 pg/mL; P < 0.001) and bioactive [[FGF21]] (β = 393.200 pg/mL; P <0.001), independent of sex, age, and body mass index. Patients with cachexia exhibited the highest [[FGF21]] levels. Clarification is needed to determine whether this is an adaptive response to nutrient deprivation in disease-related cachexia or whether the increased [[FGF21]] values contribute to the catabolic state.
|mesh-terms=* Aged
* Aged, 80 and over
* Cachexia
* Cross-Sectional Studies
* Female
* Fibroblast Growth Factors
* Gelatinases
* Humans
* Male
* Membrane Proteins
* Pilot Projects
* Prospective Studies
* Serine Endopeptidases
* Weight Loss
|keywords=* Aging
* Anorexia
* Biomarker
* Cachexia
* Fibroblast growth factor 21
|full-text-url=https://sci-hub.do/10.1016/j.nut.2018.11.004
}}
{{medline-entry
|title=Impact of aging and caloric restriction on fibroblast growth factor 21 signaling in rat white adipose tissue.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30620889
|abstract=Caloric restriction (CR) suppresses age-related pathophysiology and extends lifespan. We recently reported that metabolic remodeling of white adipose tissue (WAT) plays an important role in the beneficial actions of CR; however, the detailed molecular mechanisms of this remodeling remain to be established. In the present study, we aimed to identify CR-induced alterations in the expression of fibroblast growth factor 21 ([[FGF21]]), a regulator of lipid and glucose metabolism, and of its downstream signaling mediators in liver and WAT, across the lifespan of rats. We evaluated groups of rats that had been either fed ad libitum or calorie restricted from 3 months of age and were euthanized at 3.5, 9, or 24 months of age, under fed and fasted conditions. The expression of [[FGF21]] mRNA and/or protein increased with age in liver and WAT. Interestingly, in the WAT of 9-month-old fed rats, CR further upregulated [[FGF21]] expression and eliminated the aging-associated reductions in the expression of [[FGFR1]] and beta-klotho (KLB; [[FGF21]] receptor complex). It also enhanced the expression of [[FGF21]] targets, including glucose transporter 1 and peroxisome proliferator-activated receptor (PPAR)γ coactivator-1α. The analysis of transcriptional regulators of Fgf21 suggested that aging and CR might upregulate Fgf21 expression via different mechanisms. In adipocytes in vitro, constitutive [[FGF21]] overexpression upregulated the [[FGF21]] receptor complex and [[FGF21]] targets at the mRNA or protein level. Thus, both aging and CR induced [[FGF21]] expression in rat WAT; however, only CR activated [[FGF21]] signaling. Our results suggest that [[FGF21]] signaling contributes to the CR-induced metabolic remodeling of WAT, likely activating glucose uptake and mitochondrial biogenesis.
|mesh-terms=* 3T3-L1 Cells
* Adipose Tissue, White
* Aging
* Animals
* Caloric Restriction
* Fibroblast Growth Factors
* Glucose Transporter Type 1
* Male
* Mice
* Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
* Rats
* Rats, Wistar
* Signal Transduction
|keywords=* Caloric restriction
* Fibroblast growth factor 21
* Glucose transporter 1
* White adipose tissue
* β-Klotho
|full-text-url=https://sci-hub.do/10.1016/j.exger.2019.01.001
}}
{{medline-entry
|title=Kotho and aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30557478
|abstract=Three fibroblast growth factor(FGF) members, [[FGF19]], [[FGF21]], and [[FGF23]], function as endocrine factors that regulate various metabolic processes. The unique feature of these endo- crine FGFs is the fact that they require Klotho proteins to bind to their cognate FGF recep- tors. Defects in Klotho or [[FGF23]] result in disturbed mineral metabolism and accelerated aging. The aging phenotypes can be alleviated by correcting phosphate imbalance, leading us to hypothesize that phosphate accelerates aging. In contrast, overexpression of [[FGF21]] extends life span in mice. Thus, the FGF-Klotho endocrine axes have emerged as key regula- tors of the aging process and are regarded as potential therapeutic targets for the treatment of age-related disorders.
|mesh-terms=* Aging
* Animals
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Longevity
* Mice

}}
{{medline-entry
|title=The Klotho proteins in health and disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30455427
|abstract=The Klotho proteins, αKlotho and βKlotho, are essential components of endocrine fibroblast growth factor (FGF) receptor complexes, as they are required for the high-affinity binding of [[FGF19]], [[FGF21]] and [[FGF23]] to their cognate FGF receptors (FGFRs). Collectively, these proteins form a unique endocrine system that governs multiple metabolic processes in mammals. [[FGF19]] is a satiety hormone that is secreted from the intestine on ingestion of food and binds the βKlotho-[[FGFR4]] complex in hepatocytes to promote metabolic responses to feeding. By contrast, under fasting conditions, the liver secretes the starvation hormone [[FGF21]], which induces metabolic responses to fasting and stress responses through the activation of the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system following binding to the βKlotho-FGFR1c complex in adipocytes and the suprachiasmatic nucleus, respectively. Finally, [[FGF23]] is secreted by osteocytes in response to phosphate intake and binds to αKlotho-FGFR complexes, which are expressed most abundantly in renal tubules, to regulate mineral metabolism. Growing evidence suggests that the FGF-Klotho endocrine system also has a crucial role in the pathophysiology of ageing-related disorders, including diabetes, cancer, arteriosclerosis and chronic kidney disease. Therefore, targeting the FGF-Klotho endocrine axes might have therapeutic benefit in multiple systems; investigation of the crystal structures of FGF-Klotho-FGFR complexes is paving the way for the development of drugs that can regulate these axes.
|mesh-terms=* Aging
* Animals
* Biomarkers
* Birds
* Cardiovascular Diseases
* Endocrine System Diseases
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Hypothalamo-Hypophyseal System
* Kidney Diseases
* Mammals
* Phosphates
* Pituitary-Adrenal System

|full-text-url=https://sci-hub.do/10.1038/s41581-018-0078-3
}}
{{medline-entry
|title=Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30071357
|abstract=Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people at risk for increased vulnerability, disease, injury, and mortality. However, complementary molecular frailty biomarkers or ideally biomarker panels have not yet been identified. We conducted a systematic search to identify biomarker candidates for a frailty biomarker panel. Gene expression databases were searched (http://genomics.senescence.info/genes including GenAge, AnAge, LongevityMap, CellAge, DrugAge, Digital Aging Atlas) to identify genes regulated in aging, longevity, and age-related diseases with a focus on secreted factors or molecules detectable in body fluids as potential frailty biomarkers. Factors broadly expressed, related to several "hallmark of aging" pathways as well as used or predicted as biomarkers in other disease settings, particularly age-related pathologies, were identified. This set of biomarkers was further expanded according to the expertise and experience of the authors. In the next step, biomarkers were assigned to six "hallmark of aging" pathways, namely (1) inflammation, (2) mitochondria and apoptosis, (3) calcium homeostasis, (4) fibrosis, (5) NMJ (neuromuscular junction) and neurons, (6) cytoskeleton and hormones, or (7) other principles and an extensive literature search was performed for each candidate to explore their potential and priority as frailty biomarkers. A total of 44 markers were evaluated in the seven categories listed above, and 19 were awarded a high priority score, 22 identified as medium priority and three were low priority. In each category high and medium priority markers were identified. Biomarker panels for frailty would be of high value and better than single markers. Based on our search we would propose a core panel of frailty biomarkers consisting of (1) [[CXCL10]] (C-X-C motif chemokine ligand 10), IL-6 (interleukin 6), [[CX3CL1]] (C-X3-C motif chemokine ligand 1), (2) [[GDF15]] (growth differentiation factor 15), [[FNDC5]] (fibronectin type III domain containing 5), vimentin (VIM), (3) regucalcin (RGN/SMP30), calreticulin, (4) [[PLAU]] (plasminogen activator, urokinase), [[AGT]] (angiotensinogen), (5) [[BDNF]] (brain derived neurotrophic factor), progranulin (PGRN), (6) α-klotho (KL), [[FGF23]] (fibroblast growth factor 23), [[FGF21]], leptin (LEP), (7) miRNA (micro Ribonucleic acid) panel (to be further defined), [[AHCY]] (adenosylhomocysteinase) and [[KRT18]] (keratin 18). An expanded panel would also include (1) pentraxin (PTX3), sVCAM/ICAM (soluble vascular cell adhesion molecule 1/Intercellular adhesion molecule 1), defensin α, (2) [[APP]] (amyloid beta precursor protein), LDH (lactate dehydrogenase), (3) [[S100B]] (S100 calcium binding protein B), (4) TGFβ (transforming growth factor beta), PAI-1 (plasminogen activator inhibitor 1), [[TGM2]] (transglutaminase 2), (5) sRAGE (soluble receptor for advanced glycosylation end products), [[HMGB1]] (high mobility group box 1), C3/C1Q (complement factor 3/1Q), ST2 (Interleukin 1 receptor like 1), agrin (AGRN), (6) IGF-1 (insulin-like growth factor 1), resistin (RETN), adiponectin (ADIPOQ), ghrelin (GHRL), growth hormone (GH), (7) microparticle panel (to be further defined), GpnmB (glycoprotein nonmetastatic melanoma protein B) and lactoferrin (LTF). We believe that these predicted panels need to be experimentally explored in animal models and frail cohorts in order to ascertain their diagnostic, prognostic and therapeutic potential.
|mesh-terms=* Aged
* Aging
* Amyloid beta-Peptides
* Amyloid beta-Protein Precursor
* Animals
* Apoptosis
* Biomarkers
* Fibronectins
* Frailty
* Genetic Association Studies
* Growth Differentiation Factor 15
* Humans
* Insulin-Like Growth Factor I
* Interleukin-1 Receptor-Like 1 Protein
* Membrane Glycoproteins
* MicroRNAs
* Signal Transduction
|keywords=* Age-related diseases
* Biomarker panel
* Frailty
* Hallmark of aging pathways
|full-text-url=https://sci-hub.do/10.1016/j.arr.2018.07.004
}}
{{medline-entry
|title=Aging is associated with increased [[FGF21]] levels but unaltered [[FGF21]] responsiveness in adipose tissue.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30043445
|abstract=Fibroblast growth factor 21 ([[FGF21]]) has been proposed to be an antiaging hormone on the basis of experimental studies in rodent models. However, circulating [[FGF21]] levels are increased with aging in rodents and humans. Moreover, despite the metabolic health-promoting effects of [[FGF21]], the levels of this hormone are increased under conditions such as obesity and diabetes, an apparent incongruity that has been attributed to altered tissue responsiveness to [[FGF21]]. Here, we investigated serum [[FGF21]] levels and expression of genes encoding components of the [[FGF21]]-response molecular machinery in adipose tissue from healthy elderly individuals (≥70 years old) and young controls. Serum [[FGF21]] levels were increased in elderly individuals and were positively correlated with insulinemia and HOMA-IR, indices of mildly deteriorated glucose homeostasis. Levels of β-Klotho, the coreceptor required for cellular responsiveness to [[FGF21]], were increased in subcutaneous adipose tissue from elderly individuals relative to those from young controls, whereas FGF receptor-1 levels were unaltered. Moreover, total ERK1/2 protein levels were decreased in elderly individuals in association with an increase in the ERK1/2 phosphorylation ratio relative to young controls. Adipose explants from aged and young mice respond similarly to [[FGF21]] "ex vivo". Thus, in contrast to what is observed in obesity and diabetes, high levels of [[FGF21]] in healthy aging are not associated with repressed [[FGF21]]-responsiveness machinery in adipose tissue. The lack of evidence for impaired [[FGF21]] responsiveness in adipose tissue establishes a distinction between alterations in the [[FGF21]] endocrine system in aging and chronic metabolic pathologies.
|mesh-terms=* Adipose Tissue
* Adult
* Aged, 80 and over
* Aging
* Biomarkers
* Case-Control Studies
* Female
* Fibroblast Growth Factors
* Humans
* Inflammation
* Male

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156525
}}
{{medline-entry
|title=Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29988085
|abstract=Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10 ) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in [[RARB]] locus for carbohydrate intake and a rare variant in [[DRAM1]] locus for protein intake, and corroborating earlier [[FGF21]] and [[FTO]] findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for [[DRAM1]]. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.
|mesh-terms=* Aged
* Aging
* Alpha-Ketoglutarate-Dependent Dioxygenase FTO
* Cohort Studies
* Energy Intake
* European Continental Ancestry Group
* Female
* Fibroblast Growth Factors
* Genetic Loci
* Genetic Predisposition to Disease
* Genome-Wide Association Study
* Genomics
* Genotype
* Heart Diseases
* Humans
* Male
* Membrane Proteins
* Middle Aged
* Nutrients
* Obesity
* Polymorphism, Single Nucleotide
* Receptors, Retinoic Acid

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326896
}}
{{medline-entry
|title=Human Aging and Longevity Are Characterized by High Levels of Mitokines.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29955888
|abstract=Mitochondrial stress elicits the production of stress response molecules indicated as mitokines, including fibroblast growth factor 21 ([[FGF21]]), growth differentiation factor 15 ([[GDF15]]), and humanin (HN). Many diseases are characterized by progressive mitochondrial dysfunction with alterations of mitokine secretion. It is still controversial whether healthy aging and extreme longevity are accompanied by an altered production of mitokines. We analyzed [[FGF21]], HN, and [[GDF15]] plasma levels in 693 subjects aged from 21 to 113 years, and the association of these mitokines with parameters of health status. [[FGF21]], HN, and [[GDF15]] resulted increased in old age, with the highest levels found in centenarians. These molecules are associated with worsened parameters (such as handgrip strength, insulin sensitivity, triglycerides), particularly in 70-year-old persons, and their levels are inversely correlated with survival in the oldest subjects. Considering the positive biological effect of these molecules, our results can be interpreted in the framework of the hormetic paradigm as an attempt of the cells/tissues to cope with a stress that can have beneficial or detrimental effects depending on its intensity. Finally, persons with Down Syndrome (characterized by accelerated aging) have higher levels of [[GDF15]] and HN with respect to their siblings, suggesting that these molecules, especially [[GDF15]], could be considered markers of biological age.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Biomarkers
* Down Syndrome
* Female
* Fibroblast Growth Factors
* Growth Differentiation Factor 15
* Humans
* Intracellular Signaling Peptides and Proteins
* Longevity
* Male
* Middle Aged
* Mitochondria
* Surveys and Questionnaires
* Unfolded Protein Response
|keywords=* Centenarians
* FGF21
* GDF15
* Humanin
* Mortality
|full-text-url=https://sci-hub.do/10.1093/gerona/gly153
}}
{{medline-entry
|title=[Fibroblast growth factor-21 as a marker of premature aging in young and middled-aged men with type 2 diabetes].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29634140
|abstract=To investigate the impact of fibroblast growth factor 21 (FGF-21) on the severity of androgen deficiency in young and middle-aged men with type 2 diabetes mellitus. The study comprised 100 men with type 2 diabetes mellitus, cardiovascular multi-morbidity, obesity and androgen deficiency (study group) and 20 healthy men aged 35-50 years. The study group was further divided into two subgroups. Patients of the subgroup 1 received the standard treatment for type 2 diabetes and cardiovascular disease. Patients of the subgroup two were treated with conventional therapy concurrently with testosterone undecanoate. The baseline examination included the following parameters: glycated hemoglobin, total testosterone, prolactin, thyroid stimulating hormone and blood FGF-21. At nine months after the treatment, the blood levels of glycated hemoglobin, [[FGF21]] and testosterone were re-examined. The evaluation of the severity of androgen deficiency was carried out using the ICEF-5 questionnaire and the Aging Males Symptoms scale (AMS). In the study group, the mean FGF-21 level was 2.7 times higher, and the total testosterone level was 2-2.5 times lower than in the control group (p<0.05). A negative correlation was found between the blood levels of FGF-21 and total testosterone (r=-0.41, p<0.05). At nine months post treatment, the subgroup with testosterone undecanoate administered as add-on therapy showed a further decrease in FGF-21 levels and improved androgen deficiency symptoms. FGF-21 is one of the markers for type 2 diabetes, cardiovascular multi-morbidity, obesity and androgen deficiency. Given the association of FGF-21 with androgen deficiency, it can be assumed that FGF-21 plays a role in premature aging. Treatment of androgen deficiency as add-on therapy to the standard treatment of this category of patients improves their prognosis and the quality of life. Young and middle-aged men with type 2 diabetes should undergo regular screening for androgen deficiency with the purpose of its early diagnosis and timely treatment. The detection of elevated levels of FGF-21 in young and middle-aged men with type 2 diabetes mellitus and cardiovascular multi-morbidity may indicate premature aging and requires preventive measures.
|mesh-terms=* Adult
* Aging, Premature
* Androgens
* Biomarkers
* Diabetes Mellitus, Type 2
* Early Diagnosis
* Fibroblast Growth Factors
* Humans
* Male
* Middle Aged
* Surveys and Questionnaires
* Testosterone
|keywords=* androgen deficiency
* cardiovascular diseases
* diabetes mellitus type 2
* fibroblast growth factor 21
* obesity
* premature aging

}}
{{medline-entry
|title=Fibroblast growth factor 21 delayed endothelial replicative senescence and protected cells from H O -induced premature senescence through [[SIRT1]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29118911
|abstract=Vascular aging is an independent risk factor for age-related diseases, including atherosclerosis. Fibroblast growth factor 21 ([[FGF21]]) has been widely recognized as a metabolic regulator that is elevated in response to caloric and nutritional restrictions. Recent studies have demonstrated its emerging role as a pro-longevity hormone, but its effects on the senescence of human umbilical vascular endothelial cells (HUVECs) remain unclear. In the present study, we explored the anti-senescence effects and underlying mechanism of [[FGF21]] on HUVECs. Co-cultivation of HUVECs with 5 ng/mL [[FGF21]] significantly attenuated the phenotype changes of cells during [i]in vitro[/i] subculture, including increased senescent population, decreased proliferation rate, decreased [[SIRT1]] and elevated P53 and P21 protein levels. [[FGF21]] also protected HUVECs from H O -induced cell damage, including premature cell senescence, intracellular accumulation of reactive oxygen species, increased DNA damage, decreased [[SIRT1]] protein level and elevated protein levels of VCAM-1, ICAM-1, P53 and P21. Transient knockdown of [i][[SIRT1]][/i] in HUVECs significantly suppressed the protective effects of [[FGF21]] for the rescue of H O -induced premature senescence and DNA damage, which suggests that the anti-senescence effect of [[FGF21]] on HUVECs is [[SIRT1]]-dependent. These results support the potential of [[FGF21]] as a therapeutic target for postponing vascular aging and preventing age-related vascular diseases.

|keywords=* Fibroblast growth factor 21
* HUVEC
* SIRT1
* oxidative stress-induced premature senescence
* replicative senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666058
}}
{{medline-entry
|title=Integrated stress response stimulates [[FGF21]] expression: Systemic enhancer of longevity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28844867
|abstract=[[FGF21]] is a multifunctional metabolic and stress hormone which is normally expressed in liver but cellular stress, e.g. mitochondrial or endoplasmic reticulum (ER) stress, can induce its expression and subsequent secretion from several mammalian tissues. The stress kinases of the integrated stress response (ISR) pathway stimulate the expression of [[FGF21]] through the activation of [[ATF4]] transcription factor, thus enhancing cellular stress resistance. The metabolic and stress-inducible transactivation mechanisms of [[FGF21]] gene are mostly mediated through separate pathways. [[FGF21]] is an interorgan regulator which can alleviate many age-related metabolic and stress disorders, e.g. through the activation of AMPK signaling. [[FGF21]] signaling is also involved in circadian and torpor regulation. Given that circulating [[FGF21]] can attenuate organelle stress, e.g. mitochondrial and ER stresses, it resembles a stress-induced cell non-autonomous regulation of proteostasis and longevity present in model organisms. The overexpression of [[FGF21]] can even extend the lifespan of mice, probably by improving the healthspan. We will clarify the positive and negative signaling mechanisms which control the stress-related expression of [[FGF21]] through the ISR pathway. Moreover, we will examine the role of [[FGF21]] as an interorgan coordinator of survival functions in metabolic and stress disorders. We conclude that [[FGF21]] can be viewed as a cell non-autonomous enhancer of longevity in mammals.
|mesh-terms=* Animals
* Endoplasmic Reticulum Stress
* Fibroblast Growth Factors
* Gene Expression Regulation
* Liver
* Longevity
* Mice
* Mitochondria
* Signal Transduction
|keywords=* AMPK
* Cell non-autonomous
* FGF21
* Healthspan
* Klotho
* Lifespan
* PERK
|full-text-url=https://sci-hub.do/10.1016/j.cellsig.2017.08.009
}}
{{medline-entry
|title=Fibroblast growth factor 21: a regulator of metabolic disease and health span.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28559437
|abstract=Fibroblast growth factor 21 ([[FGF21]]) is a potent endocrine regulator with physiological effects on glucose and lipid metabolism and thus garners much attention for its translational potential for the management of obesity and related metabolic syndromes. [[FGF21]] is mainly expressed in several metabolically active tissue organs, such as the liver, adipose tissue, skeletal muscle, and pancreas, with profound effects and therapeutic relevance. Emerging experimental and clinical data point to the demonstrated metabolic benefits of [[FGF21]], which include, but are not limited to, weight loss, glucose and lipid metabolism, and insulin sensitivity. In addition, [[FGF21]] also acts directly through its coreceptor β-klotho in the brain to alter light-dark cycle activity. In this review, we critically appraise current advances in understanding the physiological actions of [[FGF21]] and its role as a biomarker of various metabolic diseases, especially type 2 diabetes mellitus. We also discuss the potentially exciting role of [[FGF21]] in improving our health and prolonging our life span. This information will provide a fuller understanding for further research into [[FGF21]], as well as providing a scientific basis for potentially establishing health care guidelines for this promising molecule.
|mesh-terms=* Adipose Tissue
* Biomarkers
* Circadian Rhythm
* Diabetes Mellitus, Type 2
* Fibroblast Growth Factors
* Humans
* Insulin Resistance
* Liver
* Longevity
* Membrane Proteins
* Muscle, Skeletal
* Obesity
* Pancreas
|keywords=* biomarker
* circadian
* energy homeostasis
* life span
* lipid metabolism
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625087
}}
{{medline-entry
|title=Age-Associated Loss of [[OPA1]] in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28552492
|abstract=Mitochondrial dysfunction occurs during aging, but its impact on tissue senescence is unknown. Here, we find that sedentary but not active humans display an age-related decline in the mitochondrial protein, optic atrophy 1 ([[OPA1]]), that is associated with muscle loss. In adult mice, acute, muscle-specific deletion of Opa1 induces a precocious senescence phenotype and premature death. Conditional and inducible Opa1 deletion alters mitochondrial morphology and function but not DNA content. Mechanistically, the ablation of Opa1 leads to ER stress, which signals via the unfolded protein response (UPR) and FoxOs, inducing a catabolic program of muscle loss and systemic aging. Pharmacological inhibition of ER stress or muscle-specific deletion of [[FGF21]] compensates for the loss of Opa1, restoring a normal metabolic state and preventing muscle atrophy and premature death. Thus, mitochondrial dysfunction in the muscle can trigger a cascade of signaling initiated at the ER that systemically affects general metabolism and aging.
|mesh-terms=* Aging
* Animals
* Cellular Senescence
* Endoplasmic Reticulum Stress
* Fibroblast Growth Factors
* GTP Phosphohydrolases
* Inflammation
* Mice
* Muscle, Skeletal
* Muscular Atrophy
* Organ Size
* Unfolded Protein Response
|keywords=* FGF21
* FoxO
* Opa1
* aging
* inflammation
* mitochondria
* muscle
* oxidative stress
* sarcopenia
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462533
}}
{{medline-entry
|title=Regulation of longevity by [[FGF21]]: Interaction between energy metabolism and stress responses.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28552719
|abstract=Fibroblast growth factor 21 ([[FGF21]]) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, [[FGF21]] acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. [[FGF21]] also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. [[FGF21]] is a potent longevity factor coordinating interactions between energy metabolism and stress responses. Recent studies have revealed that [[FGF21]] treatment can alleviate many age-related metabolic disorders, e.g. atherosclerosis, obesity, type 2 diabetes, and some cardiovascular diseases. In addition, transgenic mice overexpressing [[FGF21]] have an extended lifespan. However, chronic metabolic and stress-related disorders involving inflammatory responses can provoke [[FGF21]] resistance and thus disturb healthy aging process. First, we will describe the role of [[FGF21]] in interorgan energy metabolism and explain how its functions as a stress hormone can improve healthspan. Next, we will examine both the induction of [[FGF21]] expression via the integrated stress response and the molecular mechanism through which [[FGF21]] enhances healthy aging. Finally, we postulate that [[FGF21]] resistance, similarly to insulin resistance, jeopardizes human healthspan and accelerates the aging process.
|mesh-terms=* Animals
* Chronic Disease
* Diabetes Mellitus, Type 2
* Endoplasmic Reticulum Stress
* Energy Metabolism
* Fibroblast Growth Factors
* Glucose
* Humans
* Insulin Resistance
* Lipid Metabolism
* Longevity
* Metabolic Diseases
* Mitochondria
* Obesity
* Stress, Physiological
|keywords=* AMPK
* Ageing
* FGF21
* Healthspan
* Lifespan
* miR-34a
|full-text-url=https://sci-hub.do/10.1016/j.arr.2017.05.004
}}
{{medline-entry
|title=[[FGF21]] activates AMPK signaling: impact on metabolic regulation and the aging process.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27678528
|abstract=Fibroblast growth factor 21 ([[FGF21]]) has a significant role in the regulation of energy metabolism, e.g., in the control of systemic glucose and lipid metabolism. For instance, [[FGF21]] enhances insulin sensitivity, increases glucose uptake, and thus can decrease serum hyperglycemia, while it also increases lipid oxidation and inhibits lipogenesis. AMP-activated protein kinase (AMPK) is a tissue energy sensor involved in maintaining the energy balance and tissue integrity. It is known that AMPK signaling generates an energy metabolic profile which displays a remarkable overlap with that of [[FGF21]]. There is convincing evidence that endocrine [[FGF21]] signaling activates the AMPK pathway, either directly through FGFR1/β-klotho signaling or indirectly by stimulating the secretion of adiponectin and corticosteroids, which consequently can activate AMPK signaling in their target tissues. By activating AMPK, [[FGF21]] can promote a healthy aging process and thus extend mammalian lifespan. We will examine the signaling mechanisms through which [[FGF21]] can activate the AMPK pathway and then discuss the significance of the close connection between [[FGF21]] and AMPK signaling in the control of metabolic disorders and the aging process.
|mesh-terms=* AMP-Activated Protein Kinases
* Adiponectin
* Adrenal Cortex Hormones
* Animals
* Energy Metabolism
* Fibroblast Growth Factors
* Glucose
* Humans
* Lipids
* Longevity
* Mice
|keywords=* AMPK
* Adiponectin
* Ageing
* FGF21
* Klotho
* Metabolic disorders
|full-text-url=https://sci-hub.do/10.1007/s00109-016-1477-1
}}
{{medline-entry
|title=Methionine restriction improves renal insulin signalling in aged kidneys.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27453066
|abstract=Dietary methionine restriction (MR) leads to loss of adiposity, improved insulin sensitivity and lifespan extension. The possibility that dietary MR can protect the kidney from age-associated deterioration has not been addressed. Aged (10-month old) male and female mice were placed on a MR (0.172% methionine) or control diet (0.86% methionine) for 8-weeks and blood glucose, renal insulin signalling, and gene expression were assessed. Methionine restriction lead to decreased blood glucose levels compared to control-fed mice, and enhanced insulin-stimulated phosphorylation of PKB/Akt and S6 in kidneys, indicative of improved glucose homeostasis. Increased expression of lipogenic genes and downregulation of PEPCK were observed, suggesting that kidneys from MR-fed animals are more insulin sensitive. Interestingly, renal gene expression of the mitochondrial uncoupling protein [[UCP1]] was upregulated in MR-fed animals, as were the anti-ageing and renoprotective genes Sirt1, [[FGF21]], klotho, and β-klotho. This was associated with alterations in renal histology trending towards reduced frequency of proximal tubule intersections containing vacuoles in mice that had been on dietary MR for 190days compared to control-fed mice, which exhibited a pre-diabetic status. Our results indicate that dietary MR may offer therapeutic potential in ameliorating the renal functional decline related to ageing and other disorders associated with metabolic dysfunction by enhancing renal insulin sensitivity and renoprotective gene expression.
|mesh-terms=* Aging
* Animals
* Female
* Gene Expression Regulation
* Insulin
* Kidney
* Male
* Methionine
* Mice
* Signal Transduction
|keywords=* Ageing
* Diet
* Insulin
* Kidney
* Methionine
* Renoprotection
|full-text-url=https://sci-hub.do/10.1016/j.mad.2016.07.003
}}
{{medline-entry
|title=[[FGF21]] represses cerebrovascular aging via improving mitochondrial biogenesis and inhibiting p53 signaling pathway in an AMPK-dependent manner.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27364911
|abstract=Cerebrovascular aging has a high relationship with stroke and neurodegenerative disease. In the present study, we evaluated the influence of fibroblast growth factor 21 ([[FGF21]]) on angiotensin (Ang II)-mediated cerebrovascular aging in human brain vascular smooth muscle cells (hBVSMCs). Ang II induced remarkable aging-phenotypes in hBVSMCs, including enhanced SA-β-gal staining and NBS1 protein expression. First, we used immunoblotting assay to confirm protein expression of [[FGF21]] receptor (FGFR1) and the co-receptor β-Klotho in cultured hBVSMCs. Second, we found that [[FGF21]] treatment partly prevented the aging-related changes induced by Ang II. [[FGF21]] inhibited Ang II-enhanced ROS production/superoxide anion levels, rescued the Ang II-reduced Complex IV and citrate synthase activities, and suppressed the Ang II-induced meprin protein expression. Third, we showed that [[FGF21]] not only inhibited the Ang II-induced p53 activation, but also blocked the action of Ang II on Siah-1-TRF signaling pathway which is upstream factors for p53 activation. At last, either chemical inhibition of AMPK signaling pathway by a specific antagonist Compound C or knockdown of AMPKα1/2 isoform using siRNA, successfully abolished the anti-aging action of [[FGF21]] in hBVSMCs. These results indicate that [[FGF21]] protects against Ang II-induced cerebrovascular aging via improving mitochondrial biogenesis and inhibiting p53 activation in an AMPK-dependent manner, and highlight the therapeutic value of [[FGF21]] in cerebrovascular aging-related diseases such as stroke and neurodegenerative disease.
|mesh-terms=* AMP-Activated Protein Kinases
* Angiotensin II
* Brain
* Cellular Senescence
* Collagen
* Enzyme Activation
* Fibroblast Growth Factors
* Gene Expression Regulation
* Humans
* Mitochondria
* Models, Biological
* Muscle, Smooth, Vascular
* Myocytes, Smooth Muscle
* Nuclear Proteins
* Organelle Biogenesis
* Oxidative Stress
* Signal Transduction
* Telomeric Repeat Binding Protein 2
* Tumor Suppressor Protein p53
* Ubiquitin-Protein Ligases
|keywords=* AMPK
* Aging
* FGF21
* Mitochondrial biogenesis
* p53
|full-text-url=https://sci-hub.do/10.1016/j.yexcr.2016.06.020
}}
{{medline-entry
|title=Role of mitochondrial function in cell death and body metabolism.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27100503
|abstract=Mitochondria are the key players in apoptosis and necrosis. Mitochondrial DNA (mtDNA)-depleted r0 cells were resistant to diverse apoptosis inducers such as [[TNF]]-alpha, [[[[TNF]]SF10]], staurosporine and p53. Apoptosis resistance was accompanied by the absence of mitochondrial potential loss or cytochrome c translocation. r0 cells were also resistant to necrosis induced by reactive oxygen species (ROS) donors due to upregulation of antioxidant enzymes such as manganese superoxide dismutase. Mitochondria also has a close relationship with autophagy that plays a critical role in the turnover of senescent organelles or dysfunctional proteins and may be included in 'cell death' category. It was demonstrated that autophagy deficiency in insulin target tissues such as skeletal muscle induces mitochondrial stress response, which leads to the induction of [[FGF21]] as a 'mitokine' and affects the whole body metabolism. These results show that mitochondria are not simply the power plants of cells generating ATP, but are closely related to several types of cell death and autophagy. Mitochondria affect various pathophysiological events related to diverse disorders such as cancer, metabolic disorders and aging.
|mesh-terms=* Animals
* Apoptosis
* Autophagy
* Cell Death
* DNA, Mitochondrial
* Humans
* Longevity
* Mitochondria
* Necrosis
* Stress, Physiological
* TNF-Related Apoptosis-Inducing Ligand

|full-text-url=https://sci-hub.do/10.2741/4453
}}
{{medline-entry
|title=Prolongevity hormone [[FGF21]] protects against immune senescence by delaying age-related thymic involution.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26755598
|abstract=Age-related thymic degeneration is associated with loss of naïve T cells, restriction of peripheral T-cell diversity, and reduced healthspan due to lower immune competence. The mechanistic basis of age-related thymic demise is unclear, but prior evidence suggests that caloric restriction (CR) can slow thymic aging by maintaining thymic epithelial cell integrity and reducing the generation of intrathymic lipid. Here we show that the prolongevity ketogenic hormone fibroblast growth factor 21 ([[FGF21]]), a member of the endocrine FGF subfamily, is expressed in thymic stromal cells along with FGF receptors and its obligate coreceptor, βKlotho. We found that [[FGF21]] expression in thymus declines with age and is induced by CR. Genetic gain of [[FGF21]] function in mice protects against age-related thymic involution with an increase in earliest thymocyte progenitors and cortical thymic epithelial cells. Importantly, [[FGF21]] overexpression reduced intrathymic lipid, increased perithymic brown adipose tissue, and elevated thymic T-cell export and naïve T-cell frequencies in old mice. Conversely, loss of [[FGF21]] function in middle-aged mice accelerated thymic aging, increased lethality, and delayed T-cell reconstitution postirradiation and hematopoietic stem cell transplantation (HSCT). Collectively, [[FGF21]] integrates metabolic and immune systems to prevent thymic injury and may aid in the reestablishment of a diverse T-cell repertoire in cancer patients following HSCT.
|mesh-terms=* Aging
* Animals
* Fibroblast Growth Factors
* Immunosenescence
* Mice
* Mice, Inbred C57BL
* Receptors, Antigen, T-Cell
* T-Lymphocytes
* Thymus Gland
|keywords=* FGF21
* aging
* inflammation
* metabolism
* thymus
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4743827
}}
{{medline-entry
|title=Differentiated embryo chondrocyte 1 (DEC1) is a novel negative regulator of hepatic fibroblast growth factor 21 ([[FGF21]]) in aging mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26697751
|abstract=Human differentiated embryo chondrocyte expressed gene 1 (DEC1) is frequently used as a marker of senescence in vivo. Fibroblast growth factor 21 ([[FGF21]]), a novel endocrine-like member of the FGF superfamily, is highly expressed in the liver, and [[FGF21]]-transgenic mice have extended lifespans. Thus, we hypothesized that [[FGF21]] may play a role in the DEC1-mediated aging process. In this study, DEC1 knockout (KO) mice were used to characterize the mechanism by which [[FGF21]] protects mice from aging. Aging is strongly diminished in DEC1 KO mice, which is reflected by decreased lipid levels and oxidative stress, leading to an amelioration of liver function and structure. The expression of [[FGF21]] decreased with aging in wild-type (WT) mice, whereas [[ATF4]], Phospho-ERK and Phospho-p38 expression was maintained and was accompanied by a compensatory rise of [[FGF21]] mRNA and protein expression in DEC1 KO mice. Over-expression of DEC1 markedly abolished the hepatic expression of [[FGF21]], and siRNA-mediated inhibition of endogenous DEC1 increased the expression of [[FGF21]]. DEC1 further diminished the expression of [[ATF4]] in HepG2 cells over-expressing DEC1. The induction of [[FGF21]] and [[ATF4]] at the mRNA and protein levels during the course of aging supports the view that DEC1 KO mice are able to restore the age-related imbalance of metabolism. Collectively, the data obtained in this study suggest that DEC1 is a novel negative regulator of hepatic [[FGF21]] expression.
|mesh-terms=* Aging
* Animals
* Basic Helix-Loop-Helix Transcription Factors
* Cell Line
* Fibroblast Growth Factors
* Gene Expression Regulation, Developmental
* Hepatocytes
* Homeodomain Proteins
* Liver
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
|keywords=* Aging
* DEC1
* FGF21
* Hepatic homeostasis
* Liver
|full-text-url=https://sci-hub.do/10.1016/j.bbrc.2015.12.045
}}
{{medline-entry
|title=Effect of mitochondrial stress on systemic metabolism.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26100439
|abstract=In our studies investigating the role of autophagy in systemic metabolism, we found that mitochondrial dysfunction due to autophagy deficiency in insulin target tissues, such as skeletal muscle or liver, leads to the induction of fibroblast growth factor (FGF)21 as a mitokine and protection against obesity and insulin resistance. In the following studies, we observed that metformin, one of the most widely used antidiabetic medications, induces mitochondrial stress and induces [[FGF21]] through a PERK-eIF2α-[[ATF4]] pathway, which may contribute to the antidiabetic effect of metformin. Amino acid deprivation also induced [[ATF4]] and [[FGF21]], while the role of mitochondrial dysfunction in this condition is not yet clear. These results suggest the possibility that mitochondrial stress inducing an integrated stress response can induce a mitokine response and affect systemic metabolism in a non-cell-autonomous manner, in addition to the well-recognized cell-autonomous role of mitochondrial function in metabolism.
|mesh-terms=* Animals
* Autophagy
* Biomarkers
* Energy Metabolism
* Fibroblast Growth Factors
* Humans
* Hypoglycemic Agents
* Metformin
* Mitochondria
* Mitochondrial Diseases
* Models, Biological
* Stress, Physiological
|keywords=* FGF21
* longevity
* metabolism
* mitochondrial stress
* mitokine
|full-text-url=https://sci-hub.do/10.1111/nyas.12822
}}
{{medline-entry
|title=Muscle-specific 4E-BP1 signaling activation improves metabolic parameters during aging and obesity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26121750
|abstract=Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) is a key downstream effector of mTOR complex 1 (mTORC1) that represses cap-dependent mRNA translation initiation by sequestering the translation initiation factor eIF4E. Reduced mTORC1 signaling is associated with life span extension and improved metabolic homeostasis, yet the downstream targets that mediate these benefits are unclear. Here, we demonstrated that enhanced 4E-BP1 activity in mouse skeletal muscle protects against age- and diet-induced insulin resistance and metabolic rate decline. Transgenic animals displayed increased energy expenditure; altered adipose tissue distribution, including reduced white adipose accumulation and preserved brown adipose mass; and were protected from hepatic steatosis. Skeletal muscle-specific 4E-BP1 mediated metabolic protection directly through increased translation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and enhanced respiratory function. Non-cell autonomous protection was through preservation of brown adipose tissue metabolism, which was increased in 4E-BP1 transgenic animals during normal aging and in a response to diet-induced type 2 diabetes. Adipose phenotypes may derive from enhanced skeletal muscle expression and secretion of the known myokine [[FGF21]]. Unlike skeletal muscle, enhanced adipose-specific 4E-BP1 activity was not protective but instead was deleterious in response to the same challenges. These findings indicate that regulation of 4E-BP1 in skeletal muscle may serve as an important conduit through which mTORC1 controls metabolism.
|mesh-terms=* Adaptor Proteins, Signal Transducing
* Aging
* Animals
* Carrier Proteins
* Cell Cycle Proteins
* Diabetes Mellitus, Type 2
* Eukaryotic Initiation Factors
* Fibroblast Growth Factors
* Mechanistic Target of Rapamycin Complex 1
* Mice
* Mice, Knockout
* Multiprotein Complexes
* Muscle Proteins
* Muscle, Skeletal
* Obesity
* Organ Specificity
* Oxygen Consumption
* Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
* Phosphoproteins
* Signal Transduction
* TOR Serine-Threonine Kinases
* Transcription Factors

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563739
}}
{{medline-entry
|title=Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26042208
|abstract=Circulating [[FGF21]] levels are commonly elevated in disease states. There is limited information regarding concentrations of circulating [[FGF21]] in the absence of disease, as well as age-related differences in body composition that may contribute to [[FGF21]] regulation across groups. The objectives of this study were to assess [[FGF21]] levels across age groups (childhood to elder adulthood), and investigate whether body composition indices are associated with age-related differences in circulating [[FGF21]]. We cross-sectionally analyzed serum concentrations of [[FGF21]] in 184 healthy subjects aged 5-80y (45% male). Multiple linear regression was performed to assess the independent association of categorical age (children: 5-12y, young adults: 20-29y, adults: 30-50y, older adults: 55-64y, elder adults: 65-80y) with [[FGF21]] concentration taking into account DXA-measured body composition indices [bone mineral density (BMD) and percent lean, trunk, and fat mass]. We also stratified analysis by tertile of [[FGF21]]. Incremental increases in [[FGF21]] levels were observed across age groups (youngest to highest). Age group was positively associated with [[FGF21]] level independent of body composition indices (age group variable: β=0.25, 0.24, 0.24, 0.23, all [i]P[/i]<0.0001, controlling for percent lean, BMD, percent fat, and percent trunk fat, respectively). By [[FGF21]] tertile, age group was associated with [[FGF21]] in the lowest tertile only (β=13.1, 0.19, 0.18, all P≤0.01, accounting for percent lean, fat and trunk fat, respectively), but not when accounting for BMD. Our findings in a healthy population display an age-related increase in serum [[FGF21]], highlighting a potential age effect in response to metabolic demand over the lifecourse. [[FGF21]] levels increase with age independently of body composition. At lower levels of [[FGF21]], BMD, but not other body composition parameters, attenuates the association between [[FGF21]] level and age, suggesting the metabolic demand of the skeleton may provide a link between [[FGF21]] and energy metabolism.

|keywords=* Fibroblast growth factor 21
* aging
* body composition
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450097
}}
{{medline-entry
|title=A preliminary candidate approach identifies the combination of chemerin, fetuin-A, and fibroblast growth factors 19 and 21 as a potential biomarker panel of successful aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25911468
|abstract=Although the number of centenarians is growing worldwide, the potential factors influencing the aging process remain only partially elucidated. Researchers are increasingly focusing toward biomarkers as tools to shed more light on the pathophysiology of complex phenotypes, including the ability to reach successful aging, i.e., free of major chronic diseases. We therefore conducted a case-control study examining the potential associations of multiple candidate biomarkers in healthy centenarians and sex-matched healthy elderly controls. Using a case-control study of 81 centenarians (aged ≥ 100 years) selected based on the fact that they were disease-free and 46 healthy elderly controls (aged 70-80 years), serum levels of 15 different candidate biomarkers involved in the regulation of metabolism, angiogenesis, inflammation, and bone formation were measured. Of the 15 biomarkers tested, four molecules (chemerin, fetuin-A, and fibroblast growth factors [FGF] 19 and 21) were found to be independently associated with successful aging regardless of sex. Logistic regression analysis confirmed that chemerin, fetuin-A, [[FGF19]], and [[FGF21]] were independently associated with successful aging [predicted probability (PP) = 1 / [1 1 / exp (11.832 - 0.027 × (chemerin) - 0.009 × (fetuin-A) 0.014 × ([[FGF19]]) - 0.007 × ([[FGF21]])]. The area under the curve (AUC) of predicted probability values for the four-biomarker panel revealed that it can discriminate between centenarians and elderly controls with excellent accuracy (AUC > 0.94, P < 0.001). Although preliminary in essence and limited by the low sample size and lack of replication in other independent cohorts, our data suggest an independent association between successful aging and serum chemerin, fetuin-A, [[FGF19]], and [[FGF21]], which may provide novel information on the mechanisms behind the human aging process. Whether the four-biomarker panel may predict successful aging deserves further scrutiny.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Biomarkers
* Case-Control Studies
* Chemokines
* Female
* Fetuins
* Fibroblast Growth Factors
* Humans
* Intercellular Signaling Peptides and Proteins
* Male
* Predictive Value of Tests

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409588
}}
{{medline-entry
|title=Fibroblast growth factor 21 protects mouse brain against D-galactose induced aging via suppression of oxidative stress response and advanced glycation end products formation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25871519
|abstract=Fibroblast growth factor 21 ([[FGF21]]) is a hormone secreted predominantly in the liver, pancreas and adipose tissue. Recently, it has been reported that [[FGF21]]-Transgenic mice can extend their lifespan compared with wild type counterparts. Thus, we hypothesize that [[FGF21]] may play some roles in aging of organisms. In this study d-galactose (d-gal)-induced aging mice were used to study the mechanism that [[FGF21]] protects mice from aging. The three-month-old Kunming mice were subcutaneously injected with d-gal (180mg·kg(-1)·d(-1)) for 8weeks and administered simultaneously with [[FGF21]] (1, 2 or 5mg·kg(-1)·d(-1)). Our results showed that administration of [[FGF21]] significantly improved behavioral performance of d-gal-treated mice in water maze task and step-down test, reduced brain cell damage in the hippocampus, and attenuated the d-gal-induced production of MDA, ROS and advanced glycation end products (AGEs). At the same time, [[FGF21]] also markedly renewed the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total anti-oxidation capability (T-AOC), and decreased the enhanced total cholinesterase (TChE) activity in the brain of d-gal-treated mice. The expression of aldose reductase (AR), sorbitol dehydrogenase (SDH) and member-anchored receptor for AGEs (RAGE) declined significantly after [[FGF21]] treatment. Furthermore, [[FGF21]] suppressed inflamm-aging by inhibiting IκBα degradation and NF-κB p65 nuclear translocation. The expression levels of pro-inflammatory cytokines, such as [[TNF]]-α and IL-6, decreased significantly. In conclusion, these results suggest that [[FGF21]] protects the aging mice brain from d-gal-induced injury by attenuating oxidative stress damage and decreasing AGE formation.
|mesh-terms=* Aging
* Animals
* Brain
* Cognition Disorders
* Fibroblast Growth Factors
* Galactose
* Glycation End Products, Advanced
* Inflammation Mediators
* Male
* Mice
* Oxidative Stress
* Reactive Oxygen Species
|keywords=* AGEs
* Aging
* FGF21
* Inflammation
* Oxidative stress
* d-galactose
|full-text-url=https://sci-hub.do/10.1016/j.pbb.2015.03.020
}}
{{medline-entry
|title=Cardiorespiratory fitness and visceral fat are key determinants of serum fibroblast growth factor 21 concentration in Japanese men.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25013999
|abstract=Fibroblast growth factor-21 ([[FGF21]]) is an important metabolic regulator suggested to improve glucose metabolism and prevent dyslipidemia. An [[FGF21]]-resistant state that increases circulating [[FGF21]] has been reported in obese patients. Although regular exercise prevents metabolic disease, the relationship of the fitness level to serum [[FGF21]] level and body fat distribution in humans remains poorly understood. The objective of the study was to determine the relationship among the serum [[FGF21]] concentration, cardiorespiratory fitness (CRF) level, and visceral fat area (VFA). Serum [[FGF21]] was measured by an ELISA in 166 middle-aged and elderly Japanese men (aged 30-79 y) and 25 untrained and 21 endurance-trained young men (aged 19-29 y). CRF was assessed by measuring the peak oxygen uptake (VO2peak) and VFA by magnetic resonance imaging. In the middle-aged and elderly subjects, the serum [[FGF21]] level correlated with the VO2peak (r = -0.355, P < .001) and VFA (r = 0.487, P < .001). Stepwise multiple regression analysis showed VFA to be most strongly associated with the serum [[FGF21]] level (β = .360, P < .001), and VO2peak was also an independent predictor of the serum [[FGF21]] level (β = -.174, P = .019). Furthermore, the proportion of subjects with an [[FGF21]] level below the limit of detection was significantly higher among the endurance-trained than among the untrained young men (71.4% vs 24.0%, P = .001), and the VO2peak and VFA were independently associated with an undetectable [[FGF21]] level (P < .05). CRF and VFA are key determinants of the circulating [[FGF21]] concentration.
|mesh-terms=* Adult
* Aged
* Aging
* Asian Continental Ancestry Group
* Blood Glucose
* Exercise Test
* Fibroblast Growth Factors
* Humans
* Insulin
* Intra-Abdominal Fat
* Linear Models
* Male
* Middle Aged
* Models, Biological
* Odds Ratio
* Oxygen Consumption
* Physical Endurance
* Physical Fitness
* Risk Factors
* Young Adult

|full-text-url=https://sci-hub.do/10.1210/jc.2014-1877
}}
{{medline-entry
|title=Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24935677
|abstract=Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) or control diet (0.86% methionine) for 8 weeks or 48 h. Food intake and whole-body physiology were assessed and serum/tissues analyzed biochemically. Methionine restriction in 12-month-old mice completely reversed age-induced alterations in body weight, adiposity, physical activity, and glucose tolerance to the levels measured in healthy 2-month-old control-fed mice. This was despite a significant increase in food intake in 12-month-old MR-fed mice. Methionine restriction decreased hepatic lipogenic gene expression and caused a remodeling of lipid metabolism in white adipose tissue, alongside increased insulin-induced phosphorylation of the insulin receptor (IR) and Akt in peripheral tissues. Mice restricted of methionine exhibited increased circulating and hepatic gene expression levels of [[FGF21]], phosphorylation of eIF2a, and expression of [[ATF4]], with a concomitant decrease in IRE1α phosphorylation. Short-term 48-h MR treatment increased hepatic [[FGF21]] expression/secretion and insulin signaling and improved whole-body glucose homeostasis without affecting body weight. Our findings suggest that MR feeding can reverse the negative effects of aging on body mass, adiposity, and insulin resistance through an [[FGF21]] mechanism. These findings implicate MR dietary intervention as a viable therapy for age-induced metabolic syndrome in adult humans.
|mesh-terms=* Animals
* Energy Metabolism
* Fibroblast Growth Factors
* Gene Expression
* Glucose
* Insulin Resistance
* Lipid Metabolism
* Male
* Methionine
* Mice
* Mice, Inbred C57BL
* Obesity
* Phenotype
|keywords=* activating transcription factor 4
* aging
* fibroblast growth factor 21
* lipid
* metabolism
* unfolded protein response
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331744
}}
{{medline-entry
|title=High glucose represses β-klotho expression and impairs fibroblast growth factor 21 action in mouse pancreatic islets: involvement of peroxisome proliferator-activated receptor γ signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23897951
|abstract=Circulating fibroblast growth factor 21 ([[FGF21]]) levels are elevated in diabetic subjects and correlate directly with abnormal glucose metabolism, while pharmacologically administered [[FGF21]] can ameliorate hyperglycemia. The pancreatic islet is an [[FGF21]] target, yet the actions of [[FGF21]] in the islet under normal and diabetic conditions are not fully understood. This study investigated the effects of high glucose on islet [[FGF21]] actions in a diabetic mouse model by investigating db/db mouse islet responses to exogenous [[FGF21]], the direct effects of glucose on [[FGF21]] signaling, and the involvement of peroxisome proliferator-activated receptor γ (PPARγ) in [[FGF21]] pathway activation. Results showed that both adult db/db mouse islets and normal islets treated with high glucose ex vivo displayed reduced β-klotho expression, resistance to [[FGF21]], and decreased PPARγ expression. Rosiglitazone, an antidiabetic PPARγ ligand, ameliorated these effects. Our data indicate that hyperglycemia in type 2 diabetes mellitus may lead to [[FGF21]] resistance in pancreatic islets, probably through reduction of PPARγ expression, which provides a novel mechanism for glucose-mediated islet dysfunction.
|mesh-terms=* Aging
* Animals
* Diabetes Mellitus, Type 2
* Disease Models, Animal
* Fibroblast Growth Factors
* Glucose
* Islets of Langerhans
* Male
* Membrane Proteins
* Mice
* PPAR gamma
* Phosphorylation
* Rosiglitazone
* Signal Transduction
* Thiazolidinediones

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806592
}}
{{medline-entry
|title=Fibroblast growth factor-21 is a promising dietary restriction mimetic.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23173578
|abstract=Dietary or caloric restriction (DR or CR), typically a 30%-40% reduction in ad libitum or "normal" nutritional energy levels, has been reported to extend life span and health span in diverse organisms, including mammals. Although the life span benefit of DR in primates and humans is unproven, preliminary evidence suggests that DR confers health span benefits. A serious effort is underway to discover or engineer DR mimetics. The most straightforward path to a DR mimetic requires a detailed understanding of the molecular mechanisms that underlie DR and related life span-enhancing protocols. Increased expression of fibroblast growth factor-21 ([[FGF21]]), a putative mammalian starvation master regulator, promotes many of the same beneficial physiological changes seen in DR animals, including decreased glucose levels, increased insulin sensitivity, and improved fatty acid/lipid profiles. Ectopic over-expression of [[FGF21]] in transgenic mice ([[FGF21]]-Tg) extends life span to a similar extent as DR in a recent study. [[FGF21]] may achieve these effects by attenuating growth hormone (GH)/insulin-like growth factor-1 (IGF1) signaling. Although [[FGF21]] expression does not increase during DR, and therefore is unlikely to mediate DR, it does increase during short-term starvation in rodents, which is a critical component of alternate day fasting, a DR-like protocol that also increases life span and health span in mammals. Various drugs have been reported to induce [[FGF21]], including peroxisome proliferator-activated receptor-α (PPARα) agonists such as fenofibrate, the histone deacetylase inhibitor sodium butyrate, and adenosine monophosphate (AMP) kinase activators metformin and 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR). Of these, only metformin has been reported to extend life span in mammals, and the extent of benefit is less than that seen with ectopic [[FGF21]] expression. Perhaps the most parsimonious explanation is that high, possibly un-physiological, levels of [[FGF21]] are needed to achieve maximum life span and health span benefits and that sufficiently high levels are not achieved by the identified [[FGF21]] inducers. More in-depth studies of the effects of [[FGF21]] and its inducers on longevity and health span are warranted.
|mesh-terms=* Animals
* Caloric Restriction
* Fibroblast Growth Factors
* Health
* Humans
* Longevity

|full-text-url=https://sci-hub.do/10.1089/rej.2012.1392
}}
{{medline-entry
|title=The starvation hormone, fibroblast growth factor-21, extends lifespan in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23066506
|abstract=Fibroblast growth factor-21 ([[FGF21]]) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response. Among its effects, [[FGF21]] induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity, blocks somatic growth and causes bone loss. Here we show that transgenic overexpression of [[FGF21]] markedly extends lifespan in mice without reducing food intake or affecting markers of NAD metabolism or AMP kinase and mTOR signaling. Transcriptomic analysis suggests that [[FGF21]] acts primarily by blunting the growth hormone/insulin-like growth factor-1 signaling pathway in liver. These findings raise the possibility that [[FGF21]] can be used to extend lifespan in other species.DOI:http://dx.doi.org/10.7554/eLife.00065.001.
|mesh-terms=* Adaptation, Physiological
* Adenylate Kinase
* Animals
* Bone Resorption
* Caloric Restriction
* Fasting
* Fatty Acids
* Female
* Fibroblast Growth Factors
* Gene Expression Regulation
* Growth Hormone
* Insulin Resistance
* Insulin-Like Growth Factor I
* Ketone Bodies
* Lipid Metabolism
* Liver
* Longevity
* Male
* Mice
* Mice, Transgenic
* NAD
* Oxidation-Reduction
* Signal Transduction
* TOR Serine-Threonine Kinases
* Transgenes
|keywords=* Mouse
* caloric restriction
* fibroblast growth factor
* growth hormone
* liver
* longevity
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466591
}}
{{medline-entry
|title=Klotho and βKlotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22396160
|abstract=Endocrine fibroblast growth factors (FGFs) have been recognized as hormones that regulate a variety of metabolic processes. [[FGF19]] is secreted from intestine upon feeding and acts on liver to suppress bile acid synthesis. [[FGF21]] is secreted from liver upon fasting and acts on adipose tissue to promote lipolysis and responses to fasting. [[FGF23]] is secreted from bone and acts on kidney to inhibit phosphate reabsorption and vitamin D synthesis. One critical feature of endocrine FGFs is that they require the Klotho gene family of transmembrane proteins as coreceptors to bind their cognate FGF receptors and exert their biological activities. This chapter overviews function of Klotho family proteins as obligate coreceptors for endocrine FGFs and discusses potential link between Klothos and age-related diseases.
|mesh-terms=* Aging
* Animals
* Glucuronidase
* Homeostasis
* Humans
* Membrane Proteins
* Phosphates
* Receptors, Cytoplasmic and Nuclear

|full-text-url=https://sci-hub.do/10.1007/978-1-4614-0887-1_2
}}
{{medline-entry
|title=Energy, evolution, and human diseases: an overview.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21289219
|abstract=In the symposium entitled "Transcriptional controls of energy sensing," the authors presented recent advances on 1) AMP kinase, an intracellular energy sensor; 2) [[PGC]]-1α (peroxisome proliferator-activated receptor γ co-activator 1α), a transcriptional co-activator that has powerful effects on mitochondria; 3) methylation and demethylation in response to metabolic fluctuations; and 4) [[FGF21]] (fibroblast growth factor 21) as an emerging hormone-like intercellular metabolic coordinator. This introduction places these advances within a broad overview of energy sensing and energy balance, with a focus on human evolution and disease. Four key elements of human biology are analyzed: 1) elevated body temperature; 2) complex prolonged reproductive pathways; 3) emergence of 4 large, well-defined fat depots, each with its own functional role; and 4) an immune system that is often up-regulated by nutrition-related signals, independent of the actual presence of a pathogen. We propose that an overactive immune system, including the "metabolic syndrome," was adopted evolutionarily in the distant past to help hold out against unconquerable infections such as tuberculosis, malaria, and trypanosomiasis. This immune activation is advantageous in the absence of other disease management methods, especially under conditions in which life expectancy is short. The inflammation has become a major agent of pathology in wealthy populations in whom the pathogens are a minor threat and life expectancy is long. The "Conclusions" section sketches cautiously how understanding the molecules involved in energy sensing and energy balance may lead to specific therapies for obesity and diabetes and for their complications.
|mesh-terms=* Adipose Tissue
* Biological Evolution
* Energy Metabolism
* Humans
* Immunity
* Infections
* Life Expectancy
* Obesity
* Reproduction

|full-text-url=https://sci-hub.do/10.3945/ajcn.110.001909
}}
{{medline-entry
|title=Role of [[FGF19]] induced [[FGFR4]] activation in the regulation of glucose homeostasis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20157585
|abstract=[[FGF19]], [[FGF21]], and [[FGF23]] form a unique subfamily of fibroblast growth factors. Because they contain intra-molecular disulfide bonds and show reduced affinity toward heparan sulfate located in the extracellular space, it is thought that, in contrast to other FGFs, they function as endocrine hormones. [[FGF23]] and its co-receptor alphaKlotho are involved in the control of aging, but it is not known if the same holds true for [[FGF19]], which can also signal through alphaKlotho. However, considerable evidence supports a role for [[FGF19]] in controlling various aspects of metabolism. We have recently fully characterized [[FGF19]]/FGFR/co-factor interactions and signaling, and in the current manuscript discuss the contribution of the [[FGF19]]/[[FGFR4]] axis to bile acid and glucose regulation.
|mesh-terms=* Animals
* Bile Acids and Salts
* Blood Glucose
* Fibroblast Growth Factors
* Homeostasis
* Humans
* Mice
* Receptor, Fibroblast Growth Factor, Type 4
|keywords=* FGF19
* FGF21
* FGF23
* aging
* diabetes
* fibroblast growth factors
* insulin
* metabolic diseases
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815751
}}

FGF2

2021-05-12T15:36:41Z

OdysseusBot: Новая страница: «Fibroblast growth factor 2 precursor (FGF-2) (Basic fibroblast growth factor) (bFGF) (Heparin-binding growth factor 2) (HBGF-2) [FGFB] ==Publications== {{medlin...»

Fibroblast growth factor 2 precursor (FGF-2) (Basic fibroblast growth factor) (bFGF) (Heparin-binding growth factor 2) (HBGF-2) [FGFB]

==Publications==

{{medline-entry
|title=Myokines: The endocrine coupling of skeletal muscle and bone.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31952571
|abstract=Bone and skeletal muscle are integrated organs and their coupling has been considered mainly a mechanical one in which bone serves as attachment site to muscle while muscle applies load to bone and regulates bone metabolism. However, skeletal muscle can affect bone homeostasis also in a non-mechanical fashion, i.e., through its endocrine activity. Being recognized as an endocrine organ itself, skeletal muscle secretes a panel of cytokines and proteins named myokines, synthesized and secreted by myocytes in response to muscle contraction. Myokines exert an autocrine function in regulating muscle metabolism as well as a paracrine/endocrine regulatory function on distant organs and tissues, such as bone, adipose tissue, brain and liver. Physical activity is the primary physiological stimulus for bone anabolism (and/or catabolism) through the production and secretion of myokines, such as IL-6, irisin, IGF-1, [[FGF2]], beside the direct effect of loading. Importantly, exercise-induced myokine can exert an anti-inflammatory action that is able to counteract not only acute inflammation due to an infection, but also a condition of chronic low-grade inflammation raised as consequence of physical inactivity, aging or metabolic disorders (i.e., obesity, type 2 diabetes mellitus). In this review article, we will discuss the effects that some of the most studied exercise-induced myokines exert on bone formation and bone resorption, as well as a brief overview of the anti-inflammatory effects of myokines during the onset pathological conditions characterized by the development a systemic low-grade inflammation, such as sarcopenia, obesity and aging.
|mesh-terms=* Aging
* Animals
* Bone and Bones
* Cytokines
* Exercise
* Homeostasis
* Humans
* Inflammation
* Muscle, Skeletal
* Obesity
|keywords=* Adipokines
* Inflammation
* Muscle-bone crosstalk
* Myokines
* Physical activity
|full-text-url=https://sci-hub.do/10.1016/bs.acc.2019.07.010
}}
{{medline-entry
|title=The influence of fibroblast growth factor 2 on the senescence of human adipose-derived mesenchymal stem cells during long-term culture.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31840944
|abstract=Adipose-derived mesenchymal stem cells (ASCs) exhibit great potential in regenerative medicine, and in vitro expansion is frequently necessary to obtain a sufficient number of ASCs for clinical use. Fibroblast growth factor 2 ([[FGF2]]) is a common supplement in the ASC culture medium to enhance cell proliferation. To achieve clinical applicability of ASC-based products, prolonged culture of ASCs is sometimes required to obtain sufficient quantity of ASCs. However, the effect of [[FGF2]] on ASCs during prolonged culture has not been previously determined. In this study, ASCs were subjected to prolonged in vitro culture with or without [[FGF2]]. [[FGF2]] maintained the small cell morphology and expedited proliferation kinetics in early ASC passages. After prolonged in vitro expansion, [[FGF2]]-treated ASCs exhibited increased cell size, arrested cell proliferation, and increased cellular senescence relative to the control ASCs. We observed an upregulation of [[FGFR1]]c and enhanced expression of downstream [[STAT3]] in the initial passages of [[FGF2]]-treated ASCs. The application of an [[FGFR1]] or [[STAT3]] inhibitor effectively blocked the enhanced proliferation of ASCs induced by [[FGF2]] treatment. [[FGFR1]]c upregulation and enhanced [[STAT3]] expression were lost in the later passages of [[FGF2]]-treated ASCs, suggesting that the continuous stimulation of [[FGF2]] becomes ineffective because of the refractory downstream [[FGFR1]] and the [[STAT3]] signaling pathway. In addition, no evidence of tumorigenicity was noted in vitro and in vivo after prolonged expansion of [[FGF2]]-cultured ASCs. Our data indicate that ASCs have evolved a [[STAT3]]-dependent response to continuous [[FGF2]] stimulation which promotes the initial expansion but limits their long-term proliferation.

|keywords=* cell proliferation
* cellular senescence
* fibroblast growth factor 2
* long-term culture
* mesenchymal stem cell
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103622
}}
{{medline-entry
|title=Decreased expression of [[GPC1]] in human skin keratinocytes and epidermis during ageing.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31430521
|abstract=Glypicans (GPCs) are heparan sulfate cell membrane proteoglycans containing glycosylphosphatidylinositol (GPI) anchor. They play important role in cell behavior by activating/presenting numerous growth factors and cytokines. The expression of GPCs was investigated in primary culture of skin keratinocytes sampled from healthy donors of different age. Primary keratinocytes from healthy female donors aged from 20 to 89 years old (n = 30) were either isolated from breast or abdominal skin samples (n = 27) or purchased (n = 3). GPCs expression was examined by qPCR, immunohistochemistry and western blot. Its role in proliferation induced by fibroblast growth factor 2 ([[FGF2]]) was also studied. Glypican 1 ([[GPC1]]) was the major expressed GPC in human keratinocytes. Its expression was up to two orders of magnitude higher than other GPCs and was significantly decreased with the age of the donors. It was localized at the cell surface and associated with intracellular granules. In skin sections, [[GPC1]] was mainly localized in basal layer of epidermis. Shedding of GPCs decreased the proliferative effect of [[FGF2]], confirming their role of modulator of growth factor effects on keratinocytes. These results established [[GPC1]] as an important player in epidermis biology and skin ageing.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Cell Proliferation
* Cells, Cultured
* Epidermis
* Female
* Fibroblast Growth Factor 2
* Gene Expression Regulation
* Glypicans
* Humans
* Keratinocytes
* Middle Aged
* RNA, Messenger
* Signal Transduction
* Skin
* Young Adult
|keywords=* Ageing
* Epidermis
* Glypican 1
* Human skin
* Keratinocytes
|full-text-url=https://sci-hub.do/10.1016/j.exger.2019.110693
}}
{{medline-entry
|title=Adipose-Derived Stem/Stromal Cells Recapitulate Aging Biomarkers and Show Reduced Stem Cell Plasticity Affecting Their Adipogenic Differentiation Capacity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31298565
|abstract=Stromal mesenchymal stem cells ([[MSC]]s) have the capability to self-renew and can differentiate into multiple cell types of the mesoderm germ layer, but their properties are affected by molecular aging mechanisms. [[MSC]]s can be obtained from adipose tissue termed as adipose-derived stem/stromal cells (ASCs) representing a promising tool for studying age-related diseases in detail. ASCs from young (16 weeks) and old (>108 weeks) rabbits were successfully isolated and propagated. ASCs showed the typical morphology and stained positive for CD105, Vimentin, Collagenase 1A, and negative for [[CD14]], CD90, and CD73, demonstrating their mesenchymal origin. ASCs expressed [[MSC]] markers, including [i]MYC[/i], [i]KLF4[/i], [i]CHD1[/i], [i]REST[/i], and [i]KAT6A[/i], whereas pluripotency-related genes, such as [i]NANOG[/i], [i]OCT4[/i], and [i]SOX2[/i], were not expressed. Aged ASCs showed altered protein and mRNA levels of [[APOE]], [[ATG7]], [[FGF2]], [[PTEN]], and [[SIRT1]]. Adipogenic differentiation of old visceral ASCs was significantly decreased compared with young visceral ASCs. We successfully established rabbit ASC cultures representing an [i]in vitro[/i] model for the analysis of stem cell aging mechanisms. ASCs, obtained from old female rabbits, showed age- and source-specific alteration due to aging of the donor. Stem cell plasticity was altered with age as shown by reduced adipogenic differentiation capacity.
|mesh-terms=* Adipogenesis
* Adipose Tissue
* Aging
* Animals
* Biomarkers
* Cell Differentiation
* Cell Plasticity
* Cell Proliferation
* Cells, Cultured
* Female
* Mesenchymal Stem Cells
* Rabbits
|keywords=* adipogenic differentiation
* adipose-derived stem/stromal cells
* aging biomarkers
* and stem cell plasticity
* healthy aging
|full-text-url=https://sci-hub.do/10.1089/cell.2019.0010
}}
{{medline-entry
|title=Evaluation of human mesenchymal stem cell senescence, differentiation and secretion behavior cultured on polycarbonate cell culture inserts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30372670
|abstract=Polycarbonate ([[PC]]) substrate is well suited for culturing human mesenchymal stem cells ([[MSC]]s) with high proliferation rate, low cell apoptosis rate and negligible cytotoxic effects. However, little is known about the influence of [[PC]] on [[MSC]] activity including senescence, differentiation and secretion. In this study, the [[PC]] cell culture insert was applied for human [[MSC]] culture and was compared with polystyrene (PS) and standard tissue culture plate (TCP). The results showed that [[MSC]]s were able to adhere on [[PC]] surface, exhibiting a spindle-shaped morphology. The size and distribution of focal adhesions of [[MSC]]s were similar on [[PC]] and TCP. The senescence level of [[MSC]]s on [[PC]] was comparable to that on TCP, but was significantly lower than that on PS. [[MSC]]s on [[PC]] were capable of self-renewal and differentiation into multiple cell lineages, including osteogenic and adipogenic lineages. [[MSC]]s cultured on [[PC]] secreted a higher level inflammatory cytokines and pro-angiogenic factors including [[FGF2]] and VEGF. Conclusively, [[PC]] represents a promising cell culture material for human [[MSC]]s.
|mesh-terms=* Cell Culture Techniques
* Cell Differentiation
* Cell Proliferation
* Humans
* Mesenchymal Stem Cells
* Polycarboxylate Cement
|keywords=* Polycarbonate
* cytokine secretion
* differentiation
* human mesenchymal stem cells
* senescence
|full-text-url=https://sci-hub.do/10.3233/CH-189322
}}
{{medline-entry
|title=Young bone marrow Sca-1 cells protect aged retina from ischaemia-reperfusion injury through activation of [[FGF2]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30255622
|abstract=Retinal ganglion cell apoptosis and optic nerve degeneration are prevalent in aged patients, which may be related to the decrease in bone marrow (BM) stem cell number/function because of the possible cross-talk between the two organs. This pathological process is accelerated by retinal ischaemia-reperfusion (I/R) injury. This study investigated whether young BM stem cells can regenerate and repair the aged retina after acute I/R injury. Young BM stem cell antigen 1 positive (Sca-1 ) or Sca-1 cells were transplanted into lethally irradiated aged recipient mice to generate Sca-1 and Sca-1 chimaeras, respectively. The animals were housed for 3 months to allow the young Sca-1 cells to repopulate in the BM of aged mice. Retinal I/R was then induced by elevation of intraocular pressure. Better preservation of visual function was found in Sca-1 than Sca-1 chimaeras 7 days after injury. More Sca-1 cells homed to the retina than Sca-1 cells and more cells differentiated into glial and microglial cells in the Sca-1 chimaeras. After injury, Sca-1 cells in the retina reduced host cellular apoptosis, which was associated with higher expression of fibroblast growth factor 2 ([[FGF2]]) in the Sca-1 chimaeras. Young Sca-1 cells repopulated the stem cells in the aged retina and diminished cellular apoptosis after acute I/R injury through [[FGF2]] and Akt signalling pathways.
|mesh-terms=* Aging
* Animals
* Antigens, Ly
* Apoptosis
* Bone Marrow Cells
* Bone Marrow Transplantation
* Fibroblast Growth Factor 2
* Gene Expression Regulation, Developmental
* Humans
* Membrane Proteins
* Mice
* Optic Nerve
* Reperfusion Injury
* Retina
* Retinal Ganglion Cells
* Stem Cell Transplantation
|keywords=* aging
* retinal ischaemia-reperfusion
* retinal regeneration
* stem cell homing
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237572
}}
{{medline-entry
|title=Skin-resident stem cells and wound healing.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28539548
|abstract=CD271 is common stem cell marker for the epidermis and dermis. We assessed a kinetic movement of epidermal and dermal CD271 cells in the wound healing process to elucidate the possible involvement with chronic skin ulcers. Epidermal CD271 cells were proliferated and migrated from 3 days after wounding. Purified epidermal CD271 cells expressed higher TGFβ2 and V[[EGF]]α transcripts than CD271 cells. Delayed wound healing was observed in the aged mice compared with young mice. During the wound healing process, the peak of dermal CD271 cell accumulation was delayed in aged mice compared with young mice. The expression levels of collagen-1, -3, -5, F4-80, [[EGF]], [[FGF2]], TGFβ1, and IL-1α were significantly increased in young mice compared with aged mice. Furthermore, purified dermal CD271 cells expressed higher [[FGF2]], [[EGF]], [[PDGFB]], and TGFβ1 gene transcripts than CD271 cells. These results suggested that epidermal and dermal CD271 cells were closely associated with wound healing process by producing various growth factors. Epidermal and dermal CD271 cells in chronic skin ulcer patients were significantly reduced compared with healthy controls. Thus, both epidermal and dermal stem cells can play an important role in wound healing process.
|mesh-terms=* Aging
* Animals
* Cell Movement
* Cell Proliferation
* Chronic Disease
* Disease Models, Animal
* Humans
* Mice
* Receptors, Nerve Growth Factor
* Skin
* Skin Physiological Phenomena
* Skin Ulcer
* Stem Cells
* Transforming Growth Factor beta
* Vascular Endothelial Growth Factor A
* Wound Healing
|keywords=* CD271
* stem cell
* wound healing
|full-text-url=https://sci-hub.do/10.2177/jsci.40.1
}}
{{medline-entry
|title=Regulation of skeletal muscle stem cells by fibroblast growth factors.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28249356
|abstract=Fibroblast growth factors (FGFs) are essential for self-renewal of skeletal muscle stem cells (satellite cells) and required for maintenance and repair of skeletal muscle. Satellite cells express high levels of FGF receptors 1 and 4, low levels of FGF receptor 3, and little or no detectable FGF receptor 2. Of the multiple FGFs that influence satellite cell function in culture, [[FGF2]] and [[FGF6]] are the only members that regulate satellite cell function in vivo by activating ERK MAPK, p38α/β MAPKs, [[PI3]] kinase, PLCγ and STATs. Regulation of FGF signaling is complex in satellite cells, requiring Syndecan-4, a heparan sulfate proteoglycan, as well as ß1-integrin and fibronectin. During aging, reduced responsiveness to FGF diminishes satellite cell self-renewal, leading to impaired skeletal muscle regeneration and depletion of satellite cells. Mislocalization of ß1-integrin, reductions in fibronectin, and alterations in heparan sulfate content all contribute to reduced FGF responsiveness in satellite cells. How these cell surface proteins regulate satellite cell self-renewal is incompletely understood. Here we summarize the current knowledge, highlighting the role(s) for FGF signaling in skeletal muscle regeneration, satellite cell behavior, and age-induced muscle wasting. Developmental Dynamics 246:359-367, 2017. © 2017 Wiley Periodicals, Inc.
|mesh-terms=* Aging
* Animals
* Cell Self Renewal
* Fibroblast Growth Factors
* Humans
* Muscle, Skeletal
* Satellite Cells, Skeletal Muscle
* Signal Transduction
* Stem Cells
|keywords=* FGF
* regeneration
* satellite cell
* skeletal muscle
* stem cell
|full-text-url=https://sci-hub.do/10.1002/dvdy.24495
}}
{{medline-entry
|title=Selectively Bred Rats Provide a Unique Model of Vulnerability to PTSD-Like Behavior and Respond Differentially to [[FGF2]] Augmentation Early in Life.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28205604
|abstract=Individuals respond differently to traumatic experiences, including their propensity to develop posttraumatic stress disorder (PTSD). Understanding individual differences in PTSD vulnerability will allow the development of improved prevention and treatment options. Here we characterized fear conditioning and extinction in rats selectively bred for differences in their locomotor response to a novel environment. Selectively bred high-responder (bHR) and low-responder (bLR) male rats are known to differ in their emotional reactivity on a range of measures of spontaneous anxiety- and depressive-like behaviors. We demonstrate that bHRs have facilitated extinction learning and retention compared with outbred Sprague Dawley rats, whereas bLRs show reduced extinction learning and retention. This indicates that bLRs are more vulnerable to PTSD-like behavior. Fibroblast growth factor 2 ([[FGF2]]) has previously been implicated in the development of these behavioral phenotypes and facilitates extinction learning in outbred animals, therefore we examined the effects of early-life [[FGF2]] on bHR and bLR behavior. [[FGF2]] administered on the day after birth facilitated extinction learning and retention in bHRs, but not in bLRs or control rats, during adulthood. This indicates that, under the current fear conditioning paradigm, early-life [[FGF2]] has protective effects only in resilient animals. This stands in contrast to [[FGF2]]'s ability to protect vulnerable animals in milder tests of anxiety. These results provide a unique animal model of individual differences in PTSD-like behavior, allowing the study of genetic, developmental, and environmental factors in its expression.
|mesh-terms=* Aging
* Animals
* Behavior, Animal
* Conditioning, Psychological
* Disease Susceptibility
* Environment
* Extinction, Psychological
* Fear
* Fibroblast Growth Factor 2
* Individuality
* Male
* Motor Activity
* Rats
* Rats, Inbred Strains
* Stress Disorders, Post-Traumatic

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518903
}}
{{medline-entry
|title=Decline in Proliferation and Immature Neuron Markers in the Human Subependymal Zone during Aging: Relationship to [[EGF]]- and FGF-Related Transcripts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27932973
|abstract=Neuroblasts exist within the human subependymal zone (SEZ); however, it is debated to what extent neurogenesis changes during normal aging. It is also unknown how precursor proliferation may correlate with the generation of neuronal and glial cells or how expression of growth factors and receptors may change throughout the adult lifespan. We found evidence of dividing cells in the human SEZ (n D 50) in conjunction with a dramatic age-related decline (21-103 years) of mRNAs indicative of proliferating cells (Ki67) and immature neurons (doublecortin). Microglia mRNA (ionized calcium-binding adapter molecule 1) increased during aging, whereas transcript levels of stem/precursor cells (glial fibrillary acidic protein delta and achaete-scute homolog 1), astrocytes (vimentin and pan-glial fibrillary acidic protein), and oligodendrocytes (oligodendrocyte lineage transcription factor 2) remained stable. Epidermal growth factor receptor ([[EGF]]R) and fibroblast growth factor 2 ([[FGF2]]) mRNAs increased throughout adulthood, while transforming growth factor alpha (TGFα), [[EGF]], Erb-B2 receptor tyrosine kinase 4 (ErbB4) and FGF receptor 1 ([[FGFR1]]) mRNAs were unchanged across adulthood. Cell proliferation mRNA positively correlated with [[FGFR1]] transcripts. Immature neuron and oligodendrocyte marker expression positively correlated with TGFα and ErbB4 mRNAs, whilst astrocyte transcripts positively correlated with [[EGF]], [[FGF2]], and [[FGFR1]] mRNAs. Microglia mRNA positively correlated with [[EGF]] and [[FGF2]] expression. Our findings indicate that neurogenesis in the human SEZ continues well into adulthood, although proliferation and neuronal differentiation may decline across adulthood. We suggest that mRNA expression of [[EGF]]- and FGF-related family members do not become limited during aging and may modulate neuronal and glial fate determination in the SEZ throughout human life.

|keywords=* aging
* doublecortin
* gliogenesis
* human
* neurogenesis
* proliferation
* subventricular zone
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123444
}}
{{medline-entry
|title=Dynamic changes in heparan sulfate during muscle differentiation and ageing regulate myoblast cell fate and [[FGF2]] signalling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27496348
|abstract=Satellite cells (SCs) are skeletal muscle stem cells residing quiescent around healthy muscle fibres. In response to injury or disease SCs activate, proliferate and eventually differentiate and fuse to one another to form new muscle fibres, or to existing damaged fibres to repair them. The sulfated polysaccharide heparan sulfate (HS) is a highly variable biomolecule known to play key roles in the regulation of cell fate decisions, though the changes that muscle HS undergoes during SC differentiation are unknown. Here we show that the sulfation levels of HS increase during SC differentiation; more specifically, we observe an increase in 6-O and 2-O-sulfation in N-acetylated disaccharides. Interestingly, a specific increase in 6-O sulfation is also observed in the heparanome of ageing muscle, which we show leads to promotion of [[FGF2]] signalling and satellite cell proliferation, suggesting a role for the heparanome dynamics in age-associated loss of quiescence. Addition of HS mimetics to differentiating SC cultures results in differential effects: an oversulfated HS mimetic increases differentiation and inhibits [[FGF2]] signalling, a known major promoter of SC proliferation and inhibitor of differentiation. In contrast, [[FGF2]] signalling is promoted by an N-acetylated HS mimetic, which inhibits differentiation and promotes SC expansion. We conclude that the heparanome of SCs is dynamically regulated during muscle differentiation and ageing, and that such changes might account for some of the phenotypes and signalling events that are associated with these processes.
|mesh-terms=* Aging
* Animals
* Biomimetic Materials
* Cell Differentiation
* Cell Line
* Cell Proliferation
* Disaccharides
* Female
* Fibroblast Growth Factor 2
* Gene Expression
* Heparitin Sulfate
* Lymphocytes
* Mice
* Mice, Inbred C57BL
* Muscle, Skeletal
* Myoblasts
* Primary Cell Culture
* Satellite Cells, Skeletal Muscle
* Signal Transduction

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380652
}}
{{medline-entry
|title=Novel Protein Arginine Methyltransferase 8 Isoform Is Essential for Cell Proliferation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26851891
|abstract=Identification of molecular mechanisms that regulate cellular replicative lifespan is needed to better understand the transition between a normal and a neoplastic cell phenotype. We have previously reported that low oxygen-mediated activity of [[FGF2]] leads to an increase in cellular lifespan and acquisition of regeneration competence in human dermal fibroblasts (iRC cells). Though cells display a more plastic developmental phenotype, they remain non-tumorigenic when injected into SCID mice (Page et al. [2009] Cloning Stem Cells 11:417-426; Page et al. [2011] Eng Part A 17:2629-2640) allowing for investigation of mechanisms that regulate increased cellular lifespan in a non-tumorigenic system. Analysis of chromatin modification enzymes by qRT-PCR revealed a 13.3-fold upregulation of the arginine methyltransferase [[PRMT8]] in iRC cells. Increased protein expression was confirmed in both iRC and human embryonic stem cells-the first demonstration of endogenous human [[PRMT8]] expression outside the brain. Furthermore, iRC cells express a novel [[PRMT8]] mRNA variant. Using siRNA-mediated knockdown we demonstrated that this novel variant was required for proliferation of human dermal fibroblasts (hDFs) and grade IV glioblastomas. [[PRMT8]] upregulation in a non-tumorigenic system may offer a potential diagnostic biomarker and a therapeutic target for cells in pre-cancerous and cancerous states. J. Cell. Biochem. 117: 2056-2066, 2016. © 2016 Wiley Periodicals, Inc.
|mesh-terms=* Animals
* Cell Line
* Cell Proliferation
* Dermis
* Fibroblasts
* Gene Expression Regulation, Developmental
* Heterografts
* Humans
* Isoenzymes
* Membrane Proteins
* Mice
* Mice, SCID
* Protein-Arginine N-Methyltransferases
* Up-Regulation
|keywords=* CANCER BIOLOGY
* PROLIFERATION
* PROTEIN METHYLATION
* REPROGRAMMING
* SENESCENCE
|full-text-url=https://sci-hub.do/10.1002/jcb.25508
}}
{{medline-entry
|title=Apoptosis during embryonic tissue remodeling is accompanied by cell senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26568417
|abstract=This study re-examined the dying process in the interdigital tissue during the formation of free digits in the developing limbs. We demonstrated that the interdigital dying process was associated with cell senescence, as deduced by induction of β-gal activity, mitotic arrest, and transcriptional up-regulation of p21 together with many components of the senescence-associated secretory phenotype. We also found overlapping domains of expression of members of the Btg/Tob gene family of antiproliferative factors in the regressing interdigits. Notably, Btg2 was up-regulated during interdigit remodeling in species with free digits but not in the webbed foot of the duck. We also demonstrate that oxidative stress promoted the expression of Btg2, and that [[FGF2]] and [[IGF1]] which are survival signals for embryonic limb mesenchyme inhibited Btg2 expression. Btg2 overexpression in vivo and in vitro induced all the observed changes during interdigit regression, including oxidative stress, arrest of cell cycle progression, transcriptional regulation of senescence markers, and caspase-mediated apoptosis. Consistent with the central role of p21 on cell senescence, the transcriptional effects induced by overexpression of Btg2 are attenuated by silencing p21. Our findings indicate that cell senescence and apoptosis are complementary processes in the regression of embryonic tissues and share common regulatory signals.
|mesh-terms=* Animals
* Apoptosis
* Cellular Senescence
* Chick Embryo
* Extremities
* Humans
* Immediate-Early Proteins
* Intracellular Signaling Peptides and Proteins
* Mesoderm
* Mice
* Mice, Inbred C57BL
* Oxidative Stress
* Tumor Suppressor Proteins
|keywords=* INZ
* SASP
* limb development
* programmed cell death
* senescence
* syndactyly
* β-galactosidase
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694067
}}
{{medline-entry
|title=Age-specific functional epigenetic changes in p21 and p16 in injury-activated satellite cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25447026
|abstract=The regenerative capacity of muscle dramatically decreases with age because old muscle stem cells fail to proliferate in response to tissue damage. Here, we uncover key age-specific differences underlying this proliferative decline: namely, the genetic loci of cyclin/cyclin-dependent kinase (CDK) inhibitors (CDKIs) p21 and p16 are more epigenetically silenced in young muscle stem cells, as compared to old, both in quiescent cells and those responding to tissue injury. Interestingly, phosphorylated ERK (pERK) induced in these cells by ectopic [[FGF2]] is found in association with p21 and p16 promoters, and moreover, only in the old cells. Importantly, in the old satellite cells, [[FGF2]]/pERK silences p21 epigenetically and transcriptionally, which leads to reduced p21 protein levels and enhanced cell proliferation. In agreement with the epigenetic silencing of the loci, young muscle stem cells do not depend as much as old on ectopic FGF/pERK for their myogenic proliferation. In addition, other CDKIs, such asp15(INK4B) and p27(KIP1) , become elevated in satellite cells with age, confirming and explaining the profound regenerative defect of old muscle. This work enhances our understanding of tissue aging, promoting strategies for combating age-imposed tissue degeneration.
|mesh-terms=* Age Factors
* Animals
* Cyclin-Dependent Kinase Inhibitor p16
* Cyclin-Dependent Kinase Inhibitor p21
* Epigenesis, Genetic
* Guided Tissue Regeneration
* Mice
* Mice, Inbred C57BL
* Muscle, Skeletal
* Satellite Cells, Skeletal Muscle
* Signal Transduction
|keywords=* Aging
* CDK inhibitor
* Chromatin
* Epigenetic
* MAPK
* Muscle stem cells
* Signal transduction
* Tissue regeneration
* pERK
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333004
}}
{{medline-entry
|title=Female aging alters expression of human cumulus cells genes that are essential for oocyte quality.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25276836
|abstract=Impact of female aging is an important issue in human reproduction. There was a need for an extensive analysis of age impact on transcriptome profile of cumulus cells (CCs) to link oocyte quality and developmental potential with patient's age. CCs from patients of three age groups were analyzed individually using microarrays. RT-qPCR validation was performed on independent CC cohorts. We focused here on pathways affected by aging in CCs that may explain the decline of oocyte quality with age. In CCs collected from patients >37 years, angiogenic genes including ANGPTL4, LEPR, TGFBR3, and [[FGF2]] were significantly overexpressed compared to patients of the two younger groups. In contrast genes implicated in TGF-β signaling pathway such as AMH, TGFB1, inhibin, and activin receptor were underexpressed. CCs from patients whose ages are between 31 and 36 years showed an overexpression of genes related to insulin signaling pathway such as IGFBP3, PIK3R1, and IGFBP5. A bioinformatic analysis was performed to identify the microRNAs that are potential regulators of the differentially expressed genes of the study. It revealed that the pathways impacted by age were potential targets of specific miRNAs previously identified in our CCs small RNAs sequencing.
|mesh-terms=* Adult
* Aging
* Cumulus Cells
* Female
* Gene Expression Profiling
* Gene Expression Regulation, Developmental
* Humans
* MicroRNAs
* Oocytes
* Reproducibility of Results
* Reverse Transcriptase Polymerase Chain Reaction
* Signal Transduction
* Transforming Growth Factor beta

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168028
}}
{{medline-entry
|title=Prostatic microenvironment in senescence: fibroblastic growth factors × hormonal imbalance.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24362909
|abstract=The aim was to characterize and correlate steroid hormone receptors with the [[FGF2]], [[FGF7]] and [[FGF8]] reactivities in the prostatic epithelium and stroma in senile rats. Fifty male senile rats and 10 young male rats were divided into the young (YNG), the senile groups (SE), the castrated group (CAS), the estrogen-deficient group (ED), the castrated estrogen group (CASE), and the estrogen-deficient androgen group (EDTEST). The ventral prostate was submitted to immunohistochemical and Western blotting analyses. The results showed decreased [[AR]] and ERβ levels and increased ERα in the senile animals in relation to YNG group. Increased ERα and ERβ reactivities presenting differential localization were characterized in the CASE group compared to the CAS group. Increased [[FGF2]] level was observed in the stroma of the CAS and ED groups in relation to the SE group and in the epithelium of the ED group in relation to the other groups. Increased and differential immunolocalization of [[FGF7]] levels were observed in the CAS, ED and CASE groups. The [[FGF8]] levels showed differential localization in the CAS and ED groups compared to the senile group. The intense hormone ablation was favorable to the autocrine signaling of [[FGF2]] and [[FGF8]]. [[FGF7]] could be activated in the androgen-independent via considering the increased [[FGF7]] in the castrated rats. We concluded that hormone ablation in senescence was favorable to activation or/and to fibroblast signaling in the prostatic microenvironment.
|mesh-terms=* Aging
* Animals
* Cellular Microenvironment
* Estrogens
* Fibroblast Growth Factors
* Gonadal Steroid Hormones
* Male
* Orchiectomy
* Prostate
* Rats
* Rats, Sprague-Dawley
* Receptors, Androgen
* Receptors, Estrogen
* Testosterone

|full-text-url=https://sci-hub.do/10.1007/s00418-013-1173-y
}}
{{medline-entry
|title=Intraventricular injection of FGF-2 promotes generation of oligodendrocyte-lineage cells in the postnatal and adult forebrain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22951928
|abstract=[[FGF2]] is considered a key factor in the generation of oligodendrocytes (OLs) derived from neural stem cells (NSCs) located within the subventricular zone (SVZ). Here, we have examined [[FGF2]] signaling in the forebrain of postnatal and adult mice. Using qPCR of microdissected microdomains of the dorsal SVZ (dSVZ) and lateral SVZ (lSVZ), and prominin1-sorted NSCs purified from these microdomains, we show that transcripts for FGF receptor 1 (FGFR1) and [[FGFR2]] are enriched in the dSVZ, from which OLs are largely derived, whereas [[FGFR3]] are significantly enriched within prominen1-sorted NSC of the lSVZ, which mainly generate olfactory interneurons. We show that direct administration of [[FGF2]] into the lateral ventricle increased the generation of oligodendrocyte progenitors (OPCs) throughout the SVZ, both within the dSVZ and ectopically in the lSVZ and ependymal wall of the SVZ. Furthermore, [[FGF2]] stimulated proliferation of neural progenitors (NPs) and their differentiation into OPCs. The results indicate that [[FGF2]] increased specification of OPCs, inducing NPs to follow an oligodendrocyte developmental pathway. Notably, [[FGF2]] did not block OPC differentiation and increased the number of oligodendrocytes in the periventricular white matter (PVWM) and cortex. However, [[FGF2]] markedly disrupted myelination in the PVWM. A key finding was that [[FGF2]] had equivalent actions on the generation of OPCs and myelin disruption in postnatal and adult mice. This study demonstrates a central role for [[FGF2]] in promoting oligodendrocyte generation in the developing and adult brain.
|mesh-terms=* Age Factors
* Aging
* Animals
* Animals, Newborn
* Cell Lineage
* Cerebral Ventricles
* Fibroblast Growth Factor 2
* Injections, Intraventricular
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Neurogenesis
* Oligodendroglia
* Prosencephalon

|full-text-url=https://sci-hub.do/10.1002/glia.22413
}}
{{medline-entry
|title=Differential gene expression in eyecup and retina of a mouse model of Stargardt-like macular dystrophy (STGD3).
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22199241
|abstract=To investigate differentially expressed genes in eyecup and retina of the [[ELOVL4]] transgenic mouse, a model of Stargardt-like macular dystrophy (STGD3). We examined gene and protein expression in known pathways relevant to retinal degeneration using PCR arrays, Western blotting, and immunohistochemistry. Investigations were performed on [[ELOVL4]] transgenic mice at 9 months, when 50% of rod (but no cone) photoreceptors had degenerated. Age-matched wild-type littermates served as controls. Significant expression level changes were found in only 17 of the 252 genes examined. Nine were upregulated (Fgf2, Fgfr1, Ntf5, Cbln1, Ngfr, Ntrk1, Trp53, Tlr6, and Herpud1), and eight were downregulated (Ccl22, Ccr3, Il18rap, Nf1, Ccl11, Atf6β, Rpn1, and Serp1). Overexpression of [[FGF2]] was detected at 1 month, before rod loss onset, and was maintained at high levels until cone loss (18 months). By 9 months, [[FGF2]] overexpression was seen in photoreceptor cell bodies. Increased glial fibrillary acidic protein ([[GFAP]]) expression due to glial cell reactivity followed the same time course. Levels of NGFR/p75NTR remained invariant. Although present in rod outer segments at 1 month, the macrophage chemoattracting chemokine [[CCL22]] became undetectable by 9 months, a likely consequence of progressive rod outer segment truncation. At a mid-degeneration stage, major changes in gene expression in the [[ELOVL4]] transgenic mouse retina included upregulation of Fgf2 and Fgfr1 and downregulation of Ccl22. Modulation of [[FGF2]] occurred very early, concomitant with an increase in [[GFAP]] expression. Future studies will address which factors upstream of Fgf2 could provide potential therapeutic targets to slow photoreceptor degeneration in STGD3.
|mesh-terms=* Aging
* Animals
* Blotting, Western
* Chemokine CCL22
* Chromosome Disorders
* Chromosomes, Human, Pair 6
* Disease Models, Animal
* Fibroblast Growth Factor 2
* Gene Expression Regulation
* Glial Fibrillary Acidic Protein
* Macular Degeneration
* Mice
* Mice, Transgenic
* Polymerase Chain Reaction
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Nerve Growth Factor
* Receptors, Nerve Growth Factor

|full-text-url=https://sci-hub.do/10.1167/iovs.11-8418
}}
{{medline-entry
|title=Early-life exposure to fibroblast growth factor-2 facilitates context-dependent long-term memory in developing rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20528078
|abstract=Fibroblast growth factor-2 ([[FGF2]]) is a potent neurotrophic factor that is involved in brain development and the formation of long-term memory. It has recently been shown that acute [[FGF2]], administered at the time of learning, enhances long-term memory for contextual fear conditioning as well as extinction of conditioned fear in developing rats. As other research has shown that administering [[FGF2]] on the first day of life leads to long-term morphological changes in the hippocampus, in the present study we investigated whether early life exposure to [[FGF2]] affects contextual fear conditioning, and renewal following extinction, later in life. Experiment 1 demonstrated that a single injection of [[FGF2]] on Postnatal Day (PND) 1 did not lead to any detectable changes in contextual fear conditioning in PND 16 or PND 23 rats. Experiments 2 and 3 demonstrated that 5 days of injections of [[FGF2]] (from PND 1-5) facilitated contextual fear conditioning in PND 16 and PND 23 rats. Experiment 4 demonstrated that the observed facilitation of memory was not due to [[FGF2]] increasing rats' sensitivity to foot shock. Experiment 5 showed that early life exposure to [[FGF2]] did not affect learning about a discrete conditioned stimulus, but did allow PND 16 rats to use contextual information in more complex ways, leading to context-dependent extinction of conditioned fear. These results further implicate [[FGF2]] as a critical signal involved in the development of learning and memory.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Conditioning, Classical
* Electroshock
* Extinction, Psychological
* Fear
* Fibroblast Growth Factor 2
* Foot
* Freezing Reaction, Cataleptic
* Male
* Memory
* Neuropsychological Tests
* Pain Threshold
* Rats
* Rats, Sprague-Dawley
* Space Perception

|full-text-url=https://sci-hub.do/10.1037/a0019582
}}
{{medline-entry
|title=Disruption of the Fgf2 gene activates the adipogenic and suppresses the osteogenic program in mesenchymal marrow stromal stem cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20510392
|abstract=Here we determine the Fibroblast Growth Factor-2 ([[FGF2]]) dependency of the time course of changes in bone mass in female mice. This study extends our earlier reports that knockout of the [[FGF2]] gene (Fgf2) caused low turnover bone loss in Fgf2(-/-) male mice by examining bone loss with age in Fgf2(-/-) female mice, and by assessing whether reduced bone formation is associated with differentiation of bone marrow stromal cells (BMSCs) towards the adipocyte lineage. Bone mineral density (BMD) was similar in 3-month-old female Fgf2( / ) and Fgf2(-/-) mice but was significantly reduced as early as 5 months of age in Fgf2(-/-) mice. In vivo studies showed that there was a greater accumulation of marrow fat in long bones of 14 and 20 month old Fgf2(-/-) mice compared with Fgf2( / ) littermates. To study the effect of disruption of [[FGF2]] on osteoblastogenesis and adipogenesis, BMSCs from both genotypes were cultured in osteogenic or adipogenic media. Reduced alkaline phosphatase positive (ALP), mineralized colonies and a marked increase in adipocytes were observed in Fgf2(-/-) BMSC cultures. These cultures also showed an increase in the mRNA of the adipogenic transcription factor PPARgamma2 as well as the downstream target genes aP2 and adiponectin. Treatment with exogenous [[FGF2]] blocked adipocyte formation and increased ALP colony formation and ALP activity in BMSC cultures of both genotypes. These results support an important role for endogenous [[FGF2]] in osteoblast (OB) lineage determination. Alteration in [[FGF2]] signaling may contribute to impaired OB bone formation capacity and to increased bone marrow fat accumulation both of which are characteristics of aged bone.
|mesh-terms=* Absorptiometry, Photon
* Adipocytes
* Adipogenesis
* Aging
* Animals
* Bone Density
* Bone Marrow Cells
* Cell Count
* Cell Proliferation
* Cells, Cultured
* Colony-Forming Units Assay
* Female
* Fibroblast Growth Factor 2
* Gene Deletion
* Gene Expression Regulation
* Mesenchymal Stem Cells
* Mice
* Mice, Knockout
* Osteogenesis
* Stromal Cells

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947437
}}
{{medline-entry
|title=Dopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through [[EGF]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19433789
|abstract=A reduction in dopaminergic innervation of the subventricular zone (SVZ) is responsible for the impaired proliferation of its resident precursor cells in this region in Parkinson's disease (PD). Here, we show that this effect involves [[EGF]], but not [[FGF2]]. In particular, we demonstrate that dopamine increases the proliferation of SVZ-derived cells by releasing [[EGF]] in a PKC-dependent manner in vitro and that activation of the [[EGF]] receptor ([[EGF]]R) is required for this effect. We also show that dopamine selectively expands the GFAP( ) multipotent stem cell population in vitro by promoting their self-renewal. Furthermore, in vivo dopamine depletion leads to a decrease in precursor cell proliferation in the SVZ concomitant with a reduction in local [[EGF]] production, which is reversed through the administration of the dopamine precursor levodopa (L-DOPA). Finally, we show that [[EGF]]R( ) cells are depleted in the SVZ of human PD patients compared with age-matched controls. We have therefore demonstrated a unique role for [[EGF]] as a mediator of dopamine-induced precursor cell proliferation in the SVZ, which has potential implications for future therapies in PD.
|mesh-terms=* Aging
* Animals
* Cell Differentiation
* Cell Proliferation
* Dopamine
* Enzyme Activation
* Epidermal Growth Factor
* ErbB Receptors
* Female
* Neurons
* Parkinson Disease
* Rats
* Rats, Sprague-Dawley

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689002
}}
{{medline-entry
|title=Fibroblast growth factor 2-stimulated proliferation is lower in muscle precursor cells from old rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19270036
|abstract=In aged skeletal muscle, impairments in regrowth and regeneration may be explained by a decreased responsiveness of muscle precursor cells (MPCs) to environmental cues such as growth factors. We hypothesized that impaired responsiveness to fibroblast growth factor 2 ([[FGF2]]) in MPCs from old animals would be explained by impaired [[FGF2]] signalling. We determined that 5-bromo-2'-deoxyuridine (BrdU) incorporation and cell number increase less in MPCs from 32- compared with 3-month-old rats. In the presence of [[FGF2]], we demonstrated that there were age-associated differential expression patterns for FGF receptor 1 and 2 mRNAs. Measurement of downstream signalling revealed that that mitogen-activated protein kinase/ERK kinase 1/2 (MEK1/2)-extracellular signal-regulated kinase 1/2, protein kinase C and p38 were [[FGF2]]-driven pathways in MPCs. Uniquely, protein kinase C signalling was shown to play the largest role in [[FGF2]]-stimulated proliferation in MPCs. c-Jun N-terminal kinase (JNK) signalling was ruled out as an [[FGF2]]-stimulated proliferation pathway in MPCs. Inhibition of JNK had no effect on [[FGF2]] signalling to BrdU incorporation, and [[FGF2]] treatment was associated with increased phosphorylation of p38, which inhibits, rather than stimulates, BrdU incorporation in MPCs. Surprisingly, the commonly used vehicle, dimethyl sulphoxide, rescued proliferation in MPCs from old animals. These findings provide insight for the development of effective treatment strategies that target the age-related impairments of MPC proliferation in old skeletal muscle.
|mesh-terms=* Adult Stem Cells
* Aging
* Animals
* Base Sequence
* Bromodeoxyuridine
* Cell Proliferation
* DNA Primers
* Fibroblast Growth Factor 2
* In Vitro Techniques
* JNK Mitogen-Activated Protein Kinases
* Muscle Fibers, Skeletal
* Protein Kinase C
* RNA, Messenger
* Rats
* Rats, Inbred BN
* Rats, Inbred F344
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Signal Transduction
* p38 Mitogen-Activated Protein Kinases

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821009
}}
{{medline-entry
|title=Focal adhesion kinase (FAK) expression and activation during lens development.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17417603
|abstract=Regulation of lens development involves an intricate interplay between growth factor (e.g. FGF and TGFbeta) and extracellular matrix (ECM) signaling pathways. Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays key roles in transmitting ECM signals by integrins. In this study, we delineated patterns of FAK expression and tyrosine phosphorylation (Y397) in the developing lens and investigated its regulation by [[FGF2]]. We also examined FAK expression and activation during disrupted fiber differentiation in mice expressing a dominant-negative TGFbeta receptor. FAK expression and activation (phosphorylation on Y397) was studied in embryonic and postnatal rodent lenses by in situ hybridization, immunofluorescence, and western blotting. Rat lens explants were used to investigate the effects of [[FGF2]] on FAK expression and activation. Immunofluorescence and western blotting were used to examine FAK expression and phosphorylation in transgenic mice that express a dominant-negative TGFbeta receptor. FAK is widely expressed and phosphorylated during embryonic stages of lens morphogenesis and differentiation. However, in postnatal lenses its expression and activation becomes restricted to the posterior germinative zone and the transitional zone at the lens equator. While both NH2- and COOH-terminal antibodies revealed cytoplasmic and membrane-associated staining in lens cells, the NH2-terminal antibody also showed FAK was present in fiber cell nuclei. In vitro, FAK expression and phosphorylation on Y397 were increased by concentrations of [[FGF2]] that initiate lens epithelial cell migration (10 ng/ml) and differentiation (50 ng/ml) but not proliferation (5 ng/ml). Moreover, reactivity for Y397 phosphorylated FAK is prominent in the nuclei of differentiating fibers both in vivo and in vitro. Disruption of TGFbeta-like signals by ectopic expression of a dominant-negative TGFbeta receptor (TbetaRII(D/N)) results in abnormal lens fiber differentiation in transgenic mice. While FAK expression is initiated normally in the posterior germinative zone of TbetaRII(D/N) transgenic lenses, as fiber differentiation proceeds, FAK becomes localized to a perinuclear compartment, decreases its association with the cytoskeleton and is poorly phosphorylated on Y(397). FAK is widely expressed and activated during early lens morphogenesis. During secondary lens fiber differentiation, FAK is expressed and phosphorylated on Y397 as epithelial cells exit the cell cycle, initiate migration at the equator, and undergo differentiation in the transitional zone. During terminal fiber differentiation an NH2-terminal fragment of FAK, including Y397, is translocated to the nucleus. The expression, activation, and nuclear localization of FAK are regulated, at least partly, by [[FGF2]]. FAK activity and subcellular localization are also modulated by TGFbeta-like signals. In fiber cells of TbetaRII(D/N) transgenic lenses, FAK is abnormally retained in a perinuclear compartment, loses its association with the cytoskeleton, and is poorly phosphorylated. These data suggest that integrin signaling via FAK plays important roles during lens differentiation, mediated by FGFs and TGFbeta-superfamily signals.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Embryo, Mammalian
* Enzyme Activation
* Fibroblast Growth Factor 2
* Focal Adhesion Protein-Tyrosine Kinases
* Lens, Crystalline
* Mice
* Mice, Transgenic
* Phosphorylation
* Protein-Serine-Threonine Kinases
* RNA, Messenger
* Rats
* Rats, Wistar
* Receptor, Transforming Growth Factor-beta Type II
* Receptors, Transforming Growth Factor beta
* Tissue Distribution

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642935
}}
{{medline-entry
|title=Age-related differences in articular cartilage wound healing: a potential role for transforming growth factor beta1 in adult cartilage repair.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17120792
|abstract=Objective of this study was to investigate the early wound healing reactions of immature and mature articular cartilage on experimental wound healing in the New Zealand White rabbit. The proliferation potential and glycosaminoglycan production of isolated chondrocytes of these animals was studied in an alginate culture system. A band of tissue with death chondrocytes was observed at wound edges of immature articular cartilage, whereas mature cartilage showed a significant smaller amount of dead chondrocytes. A general increase in TGFbeta1, [[FGF2]] and [[IGF1]] was observed throughout cartilage tissue with the exception of lesion edges. The observed immunonegative area appeared to correlate with the observed cell death in lesion edges. Repair in immature cartilage was indicated by chondrocyte proliferation in clusters and a decrease in defect size. No repair response was observed in mature articular cartilage defects. The alginate culture experiment demonstrated a higher proliferation rate of immature chondrocytes. Addition of recombinant TGFbeta1 increased proliferation rate and GAG production of mature chondrocytes. We were not able to further stimulate immature chondrocytes. These results indicate that TGFbeta1 addition may contribute to induce cartilage repair responses in mature cartilage as observed in immature, developing cartilage.
|mesh-terms=* Aging
* Animals
* Cartilage
* Cartilage, Articular
* Cell Culture Techniques
* Cell Proliferation
* Cells, Cultured
* Chondrocytes
* Glycosaminoglycans
* Immunohistochemistry
* Intercellular Signaling Peptides and Proteins
* Rabbits
* Time Factors
* Transforming Growth Factor beta1
* Wound Healing

|full-text-url=https://sci-hub.do/10.1007/978-0-387-34133-0_20
}}
{{medline-entry
|title=Opposing actions of fibroblast growth factor-2 on early and late oligodendrocyte lineage cells in vivo.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16005082
|abstract=In vitro studies indicate that fibroblast growth factor 2 ([[FGF2]]) has diverse effects on cells of the early and late oligodendrocyte lineage. Here, we have examined this in vivo by comparing the actions of [[FGF2]] on the developing and developed anterior medullary velum (AMV) of postnatal rats. [[FGF2]], or saline vehicle in controls, was administered into the cerebrospinal fluid of anaesthetised rats between postnatal day (P)6 and P9 either for 1 day (1d), 2d, or 3d, and AMV were analysed at P8 or P9. Immunolabelling for NG2 was used to identify oligodendrocyte progenitor cells (OPCs) and Rip for premyelinating and myelin-forming oligodendrocytes. At P6-9, the AMV was clearly demarcated into myelinated caudal and premyelinated rostral areas. The caudal AMV was populated by differentiated myelin-forming oligodendrocytes and 'adult' OPCs, whilst the rostral AMV contained mixed populations of 'perinatal' OPCs, and both premyelinating and myelin-forming oligodendrocytes. Administration of [[FGF2]] resulted in the accumulation of OPCs in both the developing and developed AMV. Notably, [[FGF2]] had a bipartite action on premyelinating oligodendrocytes, at first dramatically expanding their population throughout the premyelinated and myelinated AMV, but subsequently causing the loss of these previously generated cells. In addition, [[FGF2]] induced the loss of existing myelin-forming oligodendrocytes in the developed AMV, and arrested the generation of new myelin-forming cells in the developing AMV. This study provides evidence that [[FGF2]] has opposing positive and negative actions on early and late oligodendrocyte lineage cells in vivo.
|mesh-terms=* Aging
* Animals
* Antigens
* Cell Division
* Cell Line
* Fibroblast Growth Factor 2
* Medulla Oblongata
* Myelin Sheath
* Oligodendroglia
* Proteoglycans
* Rats
* Rats, Wistar
* Stem Cells
* Time Factors

|full-text-url=https://sci-hub.do/10.1016/j.jneuroim.2005.05.015
}}
{{medline-entry
|title=Fibroblast growth factor-2 decreases hyperoxia-induced photoreceptor cell death in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11549604
|abstract=Fibroblast growth factor-2 ([[FGF2]]) has neurotrophic effects in vitro and in vivo. It has been demonstrated to decrease photoreceptor cell death in rats exposed to constant light and in rats with an inherited defect in retinal pigmented epithelium (RPE) phagocytosis, but the effects of intravitreous injections of [[FGF2]] in mice are equivocal. In this study, we used transgenic mice with increased expression of [[FGF2]] in photoreceptors (rhodopsin promoter/[[FGF2]] transgenics) to investigate the effects of sustained increased expression of [[FGF2]] in mice with various types of photoreceptor degeneration, including rd mice that are homozygous for mutated phosphodiesterase beta subunit, Q344ter mice that undergo photoreceptor degeneration because of expression of mutated rhodopsin, and mice exposed to 75% oxygen for 1 or 2 weeks. At P21, the outer nuclear layer was markedly reduced in rd mice or Q344ter mice regardless of whether they inherited the rhodopsin promoter/[[FGF2]] transgene. However, after 2 weeks of exposure to 75% oxygen, outer nuclear layer thickness was significantly reduced in littermate control mice compared to [[FGF2]] transgenic mice (P = 0.0001). These data indicate that increased expression of [[FGF2]] in photoreceptors protects them from hyperoxia-induced damage, but does not decrease cell death related to expression of mutated proteins involved in the phototransduction pathway. This suggests that [[FGF2]] protects photoreceptors from oxidative damage, which may play a role in complex genetic diseases such as age-related macular degeneration.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Cell Death
* Fibroblast Growth Factor 2
* Humans
* Hyperoxia
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Mutation
* Photoreceptor Cells, Vertebrate
* RNA, Messenger
* Reference Values
* Retinal Degeneration
* Rhodopsin

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850459
}}
{{medline-entry
|title=Attenuation of FGF signalling in mouse beta-cells leads to diabetes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11130726
|abstract=Fibroblast growth factor (FGF) signalling has been implicated in patterning, proliferation and cell differentiation in many organs, including the developing pancreas. Here we show that the FGF receptors (FGFRs) 1 and 2, together with the ligands [[FGF1]], [[FGF2]], [[FGF4]], [[FGF5]], [[FGF7]] and [[[[FGF1]]0]], are expressed in adult mouse beta-cells, indicating that FGF signalling may have a role in differentiated beta-cells. When we perturbed signalling by expressing dominant-negative forms of the receptors, [[FGFR1]]c and FGFR2b, in the pancreas, we found that that mice with attenuated [[FGFR1]]c signalling, but not those with reduced FGFR2b signalling, develop diabetes with age and exhibit a decreased number of beta-cells, impaired expression of glucose transporter 2 and increased proinsulin content in beta-cells owing to impaired expression of prohormone convertases 1/3 and 2. These defects are all characteristic of patients with type-2 diabetes. Mutations in the homeobox gene Ipf1/Pdx1 are linked to diabetes in both mouse and human. We also show that Ipf1/Pdx1 is required for the expression of [[FGFR1]] signalling components in beta-cells, indicating that Ipf1/Pdx1 acts upstream of [[FGFR1]] signalling in beta-cells to maintain proper glucose sensing, insulin processing and glucose homeostasis.
|mesh-terms=* Aging
* Animals
* Blood Glucose
* Diabetes Mellitus, Experimental
* Diabetes Mellitus, Type 2
* Fibroblast Growth Factors
* Glucose Transporter Type 1
* Glucose Transporter Type 2
* Homeodomain Proteins
* Humans
* Insulin
* Islets of Langerhans
* Mice
* Mice, Transgenic
* Monosaccharide Transport Proteins
* Pancreas
* Receptor Protein-Tyrosine Kinases
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Receptors, Fibroblast Growth Factor
* Signal Transduction
* Trans-Activators

|full-text-url=https://sci-hub.do/10.1038/35048589
}}
{{medline-entry
|title=Changes in growth factor expression in the ageing prostate may disrupt epithelial-stromal homeostasis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10943850
|abstract=The alterations in expression of six growth factors known to be regulators of prostatic function have been examined in the ventral lobe of prostates from young adult (14 week) and ageing (1.5 year) Wistar rats. The selected growth factors were transforming growth factor beta (TGFbeta1), insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), platelet derived growth factor (PDGF), basic fibroblast growth factor ([[FGF2]]) and epidermal growth factor ([[EGF]]). The extracellular matrix growth co-factor thrombospondin (TSP) was also examined. Our study demonstrated a 2.9-fold up-regulation of TGFbeta1 (p < 0.0001), a 2.0-fold increase in [[FGF2]] (p < 0.0002), an 8.3-fold increase in IGF-II (p < 0.0007) and a 5.4-fold increase in [[EGF]] (p < 0.0001) in ageing compared to adult prostate tissue. Conversely, we observed a 2.7-fold down-regulation of IGF-I (p < 0.0005), a 1.7-fold decrease in PDGF (p < 0.0097) and a 5.8-fold decrease in TSP (p < 0.0079) in ageing rat prostate tissue. The observed alterations in growth factor expression in this study may be the result or cause of, an imbalance in the proliferative-apoptotic balance during ageing. This imbalance may explain the increase in epithelial proliferation that is characteristic of the normal ageing prostate. As in other systems it seems likely that these factors work synergistically rather than in isolation.
|mesh-terms=* Aging
* Animals
* Epidermal Growth Factor
* Epithelial Cells
* Fibroblast Growth Factor 2
* Growth Substances
* Homeostasis
* Insulin-Like Growth Factor I
* Insulin-Like Growth Factor II
* Male
* Platelet-Derived Growth Factor
* Prostate
* Rats
* Rats, Wistar
* Stromal Cells
* Thrombospondins
* Transforming Growth Factor beta
* Transforming Growth Factor beta1

|full-text-url=https://sci-hub.do/10.1023/a:1004065630631
}}
{{medline-entry
|title=Calcium currents of embryonic and adult neurons in serum-free culture.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10210170
|abstract=Calcium channels affect many neuronal functions, including membrane electrical excitability, synaptic transmission, cellular homeostasis, gene transcription, growth, and development. We used recently developed methods for serum-free culture of adult and embryonic rat neurons to study the development of voltage-sensitive calcium currents. We compared characteristics of voltage-sensitive calcium currents in neurons taken from juvenile adult (2-4 months of age) and embryonic (day 18) rats. Mean total calcium currents were 67% larger in embryonic compared to adult neurons. At both ages, calcium currents contained only high-voltage-activated components, and lacked low-voltage-activated components. High-voltage-activated currents were significantly greater in embryonic than in adult neurons, but the voltage-sensitivity was similar. Our adult cultures, but not embryonic cultures, contain basic fibroblast growth factor ([[FGF2]]), which enhances survival. We tested the effect of [[FGF2]] and found that growth in its presence caused increased calcium currents in both embryonic and adult neurons. We conclude that in neurons cultured in serum-free medium, neuronal development from embryonic to juvenile adult ages is associated with a significant reduction in voltage-sensitive calcium currents.
|mesh-terms=* Aging
* Animals
* Calcium Channels
* Calcium Channels, L-Type
* Cells, Cultured
* Culture Media, Serum-Free
* Electric Conductivity
* Embryo, Mammalian
* Neurons
* Rats
* Rats, Sprague-Dawley

|full-text-url=https://sci-hub.do/10.1016/s0361-9230(98)00147-6
}}
{{medline-entry
|title=Fibroblast growth factor promotes recruitment of skeletal muscle satellite cells in young and old rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9857210
|abstract=Although the role of satellite cells in muscle growth and repair is well recognized, understanding of the molecular events that accompany their activation and proliferation is limited. In this study, we used the single myofiber culture model for comparing the proliferative dynamics of satellite cells from growing (3-week-old), young adult (8- to 10-week-old), and old (9- to 11-month-old) rats. In these fiber cultures, the satellite cells are maintained in their in situ position underneath the fiber basement membrane. We first demonstrate that the cytoplasm of fiber-associated satellite cells can be monitored with an antibody against the extracellular signal regulated kinases 1 and 2 (ERK1 and ERK2), which belong to the mitogen-activated protein kinase (MAPK) superfamily. With this immunocytological marker, we show that the satellite cells from all three age groups first proliferate and express [[PCNA]] and MyoD, and subsequently, about 24 hr later, exit the [[PCNA]] /MyoD state and become positive for myogenin. For all three age groups, fibroblast growth factor 2 ([[FGF2]]) enhances by about twofold the number of satellite cells that are capable of proliferation, as determined by monitoring the number of cells that transit from the MAPK phenotype to the [[PCNA]] /MAPK or MyoD /MAPK phenotype. Furthermore, contrary to the commonly accepted convention, we show that in the fiber cultures [[FGF2]] does not suppress the subsequent transition of the proliferating cells into the myogenin compartment. Although myogenesis of satellite cells from growing, young adult, and old rats follows a similar program, two distinctive features were identified for satellite cells in fiber cultures from the old rats. First, a large number of MAPK cells do not appear to enter the MyoD-myogenin expression program. Second, the maximal number of proliferating satellite cells is attained a day later than in cultures from the young adults. This apparent "lag" in proliferation was not affected by hepatocyte growth factor ([[HGF]]), which has been implicated in accelerating the first round of satellite cell proliferation. [[HGF]] and [[FGF2]] were equally efficient in promoting proliferation of satellite cells in fibers from old rats. Collectively, the investigation suggests that FGF plays a critical role in the recruitment of satellite cells into proliferation.
|mesh-terms=* Aging
* Animals
* Calcium-Calmodulin-Dependent Protein Kinases
* Cell Differentiation
* Cell Division
* Cytarabine
* Fibroblast Growth Factor 2
* Hepatocyte Growth Factor
* Immunoblotting
* Immunohistochemistry
* Male
* Muscle Development
* Muscle, Skeletal
* MyoD Protein
* Myogenin
* Myosins
* Proliferating Cell Nuclear Antigen
* Protein Isoforms
* Rats
* Rats, Sprague-Dawley

|full-text-url=https://sci-hub.do/10.1177/002215549904700104
}}

FGF19

2021-05-12T15:36:38Z

OdysseusBot: Новая страница: «Fibroblast growth factor 19 precursor (FGF-19) [UNQ334/PRO533] ==Publications== {{medline-entry |title=Bile acid receptor agonists in primary biliary cholangiti...»

Fibroblast growth factor 19 precursor (FGF-19) [UNQ334/PRO533]

==Publications==

{{medline-entry
|title=Bile acid receptor agonists in primary biliary cholangitis: Regulation of the cholangiocyte secretome and downstream T cell differentiation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32123836
|abstract=Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. Approximately 30% of patients do not respond to therapy with ursodeoxycholic acid (UDCA). Previous studies have implicated increased senescence of cholangiocytes in patients who do not respond to UDCA. This may increase the release of cytokines which drive pathogenic T cell polarization. As FXR agonists are beneficial in treating UDCA non-responsive patients, the current study was designed to model the interactions between cholangiocytes and CD4 T cells to investigate potential immunomodulatory mechanisms of bile acid receptor agonists. Human cholangiocytes were co-cultured with CD4 T cells to model the biliary stress response. Senescent cholangiocytes were able to polarize T cells toward a Th17 phenotype and suppressed expression of FoxP3 ([i]P[/i] = 0.0043). Whilst FXR and TGR5 receptor agonists were unable directly to alter cholangiocyte cytokine expression, [[FGF19]] was capable of significantly reducing IL-6 release ([i]P[/i] = 0.044). Bile acid receptor expression was assessed in PBC patients with well-characterized responsiveness to UDCA therapy. A reduction in FXR staining was observed in both cholangiocytes and hepatocytes in PBC patients without adequate response to UDCA. Increased IL-6 expression by senescent cholangiocytes represents a potential mechanism by which biliary damage in PBC could contribute to excessive inflammation.

|keywords=* FGF19
* FXR
* TGR5
* autoimmunity
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996327
}}
{{medline-entry
|title=Kotho and aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30557478
|abstract=Three fibroblast growth factor(FGF) members, [[FGF19]], [[FGF21]], and [[FGF23]], function as endocrine factors that regulate various metabolic processes. The unique feature of these endo- crine FGFs is the fact that they require Klotho proteins to bind to their cognate FGF recep- tors. Defects in Klotho or [[FGF23]] result in disturbed mineral metabolism and accelerated aging. The aging phenotypes can be alleviated by correcting phosphate imbalance, leading us to hypothesize that phosphate accelerates aging. In contrast, overexpression of [[FGF21]] extends life span in mice. Thus, the FGF-Klotho endocrine axes have emerged as key regula- tors of the aging process and are regarded as potential therapeutic targets for the treatment of age-related disorders.
|mesh-terms=* Aging
* Animals
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Longevity
* Mice

}}
{{medline-entry
|title=The Klotho proteins in health and disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30455427
|abstract=The Klotho proteins, αKlotho and βKlotho, are essential components of endocrine fibroblast growth factor (FGF) receptor complexes, as they are required for the high-affinity binding of [[FGF19]], [[FGF21]] and [[FGF23]] to their cognate FGF receptors (FGFRs). Collectively, these proteins form a unique endocrine system that governs multiple metabolic processes in mammals. [[FGF19]] is a satiety hormone that is secreted from the intestine on ingestion of food and binds the βKlotho-[[FGFR4]] complex in hepatocytes to promote metabolic responses to feeding. By contrast, under fasting conditions, the liver secretes the starvation hormone [[FGF21]], which induces metabolic responses to fasting and stress responses through the activation of the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system following binding to the βKlotho-FGFR1c complex in adipocytes and the suprachiasmatic nucleus, respectively. Finally, [[FGF23]] is secreted by osteocytes in response to phosphate intake and binds to αKlotho-FGFR complexes, which are expressed most abundantly in renal tubules, to regulate mineral metabolism. Growing evidence suggests that the FGF-Klotho endocrine system also has a crucial role in the pathophysiology of ageing-related disorders, including diabetes, cancer, arteriosclerosis and chronic kidney disease. Therefore, targeting the FGF-Klotho endocrine axes might have therapeutic benefit in multiple systems; investigation of the crystal structures of FGF-Klotho-FGFR complexes is paving the way for the development of drugs that can regulate these axes.
|mesh-terms=* Aging
* Animals
* Biomarkers
* Birds
* Cardiovascular Diseases
* Endocrine System Diseases
* Fibroblast Growth Factors
* Glucuronidase
* Humans
* Hypothalamo-Hypophyseal System
* Kidney Diseases
* Mammals
* Phosphates
* Pituitary-Adrenal System

|full-text-url=https://sci-hub.do/10.1038/s41581-018-0078-3
}}
{{medline-entry
|title=Peroxisomal Acyl-CoA Oxidase Type 1: Anti-Inflammatory and Anti-Aging Properties with a Special Emphasis on Studies with LPS and Argan Oil as a Model Transposable to Aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29765501
|abstract=To clarify appropriateness of current claims for health and wellness virtues of argan oil, studies were conducted in inflammatory states. LPS induces inflammation with reduction of PGC1-[i]α[/i] signaling and energy metabolism. Argan oil protected the liver against LPS toxicity and interestingly enough preservation of peroxisomal acyl-CoA oxidase type 1 ([[ACOX1]]) activity against depression by LPS. This model of LPS-driven toxicity circumvented by argan oil along with a key anti-inflammatory role attributed to [[ACOX1]] has been here transposed to model aging. This view is consistent with known physiological role of [[ACOX1]] in yielding precursors of specialized proresolving mediators (SPM) and with characteristics of aging and related disorders including reduced PGC1-[i]α[/i] function and improvement by strategies rising [[ACOX1]] (via hormonal gut [[FGF19]] and nordihydroguaiaretic acid in metabolic syndrome and diabetes conditions) and SPM (neurodegenerative disorders, atherosclerosis, and stroke). Delay of aging to resolve inflammation results from altered production of SPM, SPM improving most aging disorders. The strategic metabolic place of [[ACOX1]], upstream of SPM biosynthesis, along with ability of [[ACOX1]] preservation/induction and SPM to improve aging-related disorders and known association of aging with drop in [[ACOX1]] and SPM, all converge to conclude that [[ACOX1]] represents a previously unsuspected and currently emerging antiaging protein.
|mesh-terms=* Acyl-CoA Oxidase
* Aging
* Animals
* Anti-Inflammatory Agents
* Disease Models, Animal
* Humans
* Lipopolysaccharides
* Oxidoreductases
* Plant Oils

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889864
}}
{{medline-entry
|title=A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27829151
|abstract=The counterregulatory response to hypoglycemia, which restores normal blood glucose levels to ensure sufficient provision of glucose to the brain, is critical for survival. To discover underlying brain regulatory systems, we performed a genetic screen in recombinant inbred mice for quantitative trait loci (QTL) controlling glucagon secretion in response to neuroglucopenia. We identified a QTL on the distal part of chromosome 7 and combined this genetic information with transcriptomic analysis of hypothalami. This revealed Fgf15 as the strongest candidate to control the glucagon response. Fgf15 was expressed by neurons of the dorsomedial hypothalamus and the perifornical area. Intracerebroventricular injection of [[FGF19]], the human ortholog of Fgf15, reduced activation by neuroglucopenia of dorsal vagal complex neurons, of the parasympathetic nerve, and lowered glucagon secretion. In contrast, silencing Fgf15 in the dorsomedial hypothalamus increased neuroglucopenia-induced glucagon secretion. These data identify hypothalamic Fgf15 as a regulator of glucagon secretion.
|mesh-terms=* Aging
* Animals
* Chromosomes, Mammalian
* Deoxyglucose
* Fibroblast Growth Factors
* Gene Silencing
* Genetic Testing
* Genome
* Glucagon
* Hypothalamus
* Mice, Inbred C57BL
* Parasympathetic Nervous System
* Quantitative Trait Loci
|keywords=* FGF15
* FGF19
* QTL mapping
* autonomic nervous system
* dorsal vagal complex
* genetic screen
* glucagon secretion
* glucose sensing
* hypothalamus
* neuroglucopenia
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120348
}}
{{medline-entry
|title=A preliminary candidate approach identifies the combination of chemerin, fetuin-A, and fibroblast growth factors 19 and 21 as a potential biomarker panel of successful aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25911468
|abstract=Although the number of centenarians is growing worldwide, the potential factors influencing the aging process remain only partially elucidated. Researchers are increasingly focusing toward biomarkers as tools to shed more light on the pathophysiology of complex phenotypes, including the ability to reach successful aging, i.e., free of major chronic diseases. We therefore conducted a case-control study examining the potential associations of multiple candidate biomarkers in healthy centenarians and sex-matched healthy elderly controls. Using a case-control study of 81 centenarians (aged ≥ 100 years) selected based on the fact that they were disease-free and 46 healthy elderly controls (aged 70-80 years), serum levels of 15 different candidate biomarkers involved in the regulation of metabolism, angiogenesis, inflammation, and bone formation were measured. Of the 15 biomarkers tested, four molecules (chemerin, fetuin-A, and fibroblast growth factors [FGF] 19 and 21) were found to be independently associated with successful aging regardless of sex. Logistic regression analysis confirmed that chemerin, fetuin-A, [[FGF19]], and [[FGF21]] were independently associated with successful aging [predicted probability (PP) = 1 / [1 1 / exp (11.832 - 0.027 × (chemerin) - 0.009 × (fetuin-A) 0.014 × ([[FGF19]]) - 0.007 × ([[FGF21]])]. The area under the curve (AUC) of predicted probability values for the four-biomarker panel revealed that it can discriminate between centenarians and elderly controls with excellent accuracy (AUC > 0.94, P < 0.001). Although preliminary in essence and limited by the low sample size and lack of replication in other independent cohorts, our data suggest an independent association between successful aging and serum chemerin, fetuin-A, [[FGF19]], and [[FGF21]], which may provide novel information on the mechanisms behind the human aging process. Whether the four-biomarker panel may predict successful aging deserves further scrutiny.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Biomarkers
* Case-Control Studies
* Chemokines
* Female
* Fetuins
* Fibroblast Growth Factors
* Humans
* Intercellular Signaling Peptides and Proteins
* Male
* Predictive Value of Tests

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409588
}}
{{medline-entry
|title=Klotho and βKlotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22396160
|abstract=Endocrine fibroblast growth factors (FGFs) have been recognized as hormones that regulate a variety of metabolic processes. [[FGF19]] is secreted from intestine upon feeding and acts on liver to suppress bile acid synthesis. [[FGF21]] is secreted from liver upon fasting and acts on adipose tissue to promote lipolysis and responses to fasting. [[FGF23]] is secreted from bone and acts on kidney to inhibit phosphate reabsorption and vitamin D synthesis. One critical feature of endocrine FGFs is that they require the Klotho gene family of transmembrane proteins as coreceptors to bind their cognate FGF receptors and exert their biological activities. This chapter overviews function of Klotho family proteins as obligate coreceptors for endocrine FGFs and discusses potential link between Klothos and age-related diseases.
|mesh-terms=* Aging
* Animals
* Glucuronidase
* Homeostasis
* Humans
* Membrane Proteins
* Phosphates
* Receptors, Cytoplasmic and Nuclear

|full-text-url=https://sci-hub.do/10.1007/978-1-4614-0887-1_2
}}
{{medline-entry
|title=Role of [[FGF19]] induced [[FGFR4]] activation in the regulation of glucose homeostasis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20157585
|abstract=[[FGF19]], [[FGF21]], and [[FGF23]] form a unique subfamily of fibroblast growth factors. Because they contain intra-molecular disulfide bonds and show reduced affinity toward heparan sulfate located in the extracellular space, it is thought that, in contrast to other FGFs, they function as endocrine hormones. [[FGF23]] and its co-receptor alphaKlotho are involved in the control of aging, but it is not known if the same holds true for [[FGF19]], which can also signal through alphaKlotho. However, considerable evidence supports a role for [[FGF19]] in controlling various aspects of metabolism. We have recently fully characterized [[FGF19]]/FGFR/co-factor interactions and signaling, and in the current manuscript discuss the contribution of the [[FGF19]]/[[FGFR4]] axis to bile acid and glucose regulation.
|mesh-terms=* Animals
* Bile Acids and Salts
* Blood Glucose
* Fibroblast Growth Factors
* Homeostasis
* Humans
* Mice
* Receptor, Fibroblast Growth Factor, Type 4
|keywords=* FGF19
* FGF21
* FGF23
* aging
* diabetes
* fibroblast growth factors
* insulin
* metabolic diseases
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815751
}}

FGF14

2021-05-12T15:36:35Z

OdysseusBot: Новая страница: «Fibroblast growth factor 14 (FGF-14) (Fibroblast growth factor homologous factor 4) (FHF-4) [FHF4] ==Publications== {{medline-entry |title=Fibroblast Growth Fac...»

Fibroblast growth factor 14 (FGF-14) (Fibroblast growth factor homologous factor 4) (FHF-4) [FHF4]

==Publications==

{{medline-entry
|title=Fibroblast Growth Factor 14 Modulates the Neurogenesis of Granule Neurons in the Adult Dentate Gyrus.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26687232
|abstract=Adult neurogenesis, the production of mature neurons from progenitor cells in the adult mammalian brain, is linked to the etiology of neurodegenerative and psychiatric disorders. However, a thorough understanding of the molecular elements at the base of adult neurogenesis remains elusive. Here, we provide evidence for a previously undescribed function of fibroblast growth factor 14 ([[FGF14]]), a brain disease-associated factor that controls neuronal excitability and synaptic plasticity, in regulating adult neurogenesis in the dentate gyrus (DG). We found that [[FGF14]] is dynamically expressed in restricted subtypes of sex determining region Y-box 2 (Sox2)-positive and doublecortin ([[DCX]])-positive neural progenitors in the DG. Bromodeoxyuridine (BrdU) incorporation studies and confocal imaging revealed that genetic deletion of Fgf14 in Fgf14 mice leads to a significant change in the proportion of proliferating and immature and mature newly born adult granule cells. This results in an increase in the late immature and early mature population of [[DCX]] and calretinin (CR)-positive neurons. Electrophysiological extracellular field recordings showed reduced minimal threshold response and impaired paired-pulse facilitation at the perforant path to DG inputs in Fgf14 compared to Fgf14 mice, supporting disrupted synaptic connectivity as a correlative read-out to impaired neurogenesis. These new insights into the biology of [[FGF14]] in neurogenesis shed light into the signaling pathways associated with disrupted functions in complex brain diseases.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Apoptosis
* Cell Count
* Cell Differentiation
* Cell Survival
* Cytoplasmic Granules
* Dentate Gyrus
* Female
* Fibroblast Growth Factors
* Gene Deletion
* Gene Expression Profiling
* Male
* Mice, Inbred C57BL
* Microtubule-Associated Proteins
* Neural Stem Cells
* Neurogenesis
* Neurons
* Neuropeptides
* Synapses
|keywords=* Adult neurogenesis
* Ataxia
* Axon initial segment
* FGF14
* Growth factors
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916041
}}

FGA

2021-05-12T15:36:31Z

OdysseusBot: Новая страница: «Fibrinogen alpha chain precursor [Contains: Fibrinopeptide A; Fibrinogen alpha chain] ==Publications== {{medline-entry |title=Goal Pursuit, Goal Adjustment, and...»

Fibrinogen alpha chain precursor [Contains: Fibrinopeptide A; Fibrinogen alpha chain]

==Publications==

{{medline-entry
|title=Goal Pursuit, Goal Adjustment, and Pain in Middle-Aged Adults Aging With Physical Disability.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31718416
|abstract= Aging with physical disability disrupts one's ability to achieve valued goals due to changes in symptoms and function. It is unclear how to cope optimally in this context. This study examined whether two possible strategies-tenacious goal pursuit (TGP) and flexible goal adjustment ([[FGA]])-were associated with reduced pain interference and depressive symptoms and greater well-being, and protected against pain intensity, and [[FGA]] was more protective with increasing age and worse physical function. Middle-aged adults with muscular dystrophy, multiple sclerosis, post-polio syndrome, or spinal cord injury ([i]N[/i] = 874; [i]M[/i] = 58.3 years, range = 46-68; [i]M[/i] = 26.2 years, range = 2-67) completed two questionnaires, a year apart. TGP and [[FGA]] use was associated with greater well-being. [[FGA]] use predicted decreased depressive symptoms. Concurrent use of both predicted decreased pain interference. Adults with disability employ a variety of goal management strategies. Findings support TGP and [[FGA]] as potential intervention targets for healthy aging with disabilities.
|mesh-terms=* Adaptation, Psychological
* Aged
* Aging
* Depression
* Disabled Persons
* Female
* Goals
* Humans
* Male
* Middle Aged
* Multiple Sclerosis
* Muscular Dystrophies
* Pain
* Postpoliomyelitis Syndrome
* Spinal Cord Injuries
|keywords=* aging
* disability
* goal management
* pain
* psychological adaptation
|full-text-url=https://sci-hub.do/10.1177/0898264319827142
}}
{{medline-entry
|title=Tenacious Goal Pursuit, Flexible Goal Adjustment, and Life Satisfaction Among Chinese Older Adult Couples.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31547780
|abstract=We aimed to examine the roles of tenacious goal pursuit (TGP) and flexible goal adjustment ([[FGA]]), mediated by positive self-perceptions of aging (PSA), in Chinese older couples' life satisfaction. Using a cross-sectional design, 245 Chinese older couples (age range: 55-93 years) completed measures of TGP, [[FGA]], PSA, and life satisfaction. The results showed that (a) spousal interrelations existed for TGP and [[FGA]]; (b) TGP and [[FGA]] had significant actor effects on life satisfaction, with [[FGA]] having a stronger effect; (c) although the partner effect of [[FGA]] did not differ between husbands and wives, husbands' TGP was positively associated with wives' life satisfaction, but not vice versa; and (d) PSA mediated the effects of TGP and [[FGA]] on life satisfaction at the actor and partner levels. These results have implications for developing couple-based interventions to enhance successful aging, with a focus on promoting both partners' accommodative coping and positive age beliefs.

|keywords=* flexible goal adjustment
* life satisfaction
* older couples
* self-perceptions of aging
* tenacious goal pursuit
|full-text-url=https://sci-hub.do/10.1177/0164027519876125
}}
{{medline-entry
|title=Association of tenacious goal pursuit and flexible goal adjustment with out-of-home mobility among community-dwelling older people.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30449015
|abstract=As people age, functional losses may limit the potential to get outside the home and participate in desired activities and community life. Coping with age-related losses has been reported to be important for psychological well-being. Hitherto is not known whether active use of coping strategies also helps maintain out-of-home mobility. We investigated how two coping strategies, tenacious goal pursuit (TGP; persistency in reaching one's goals) and flexible goal adjustment ([[FGA]]; adjusting one's goals to changed circumstances), are associated with life-space mobility and perceived autonomy in participation outdoors among community-dwelling older people. Participants (n = 186) were aged 79-93 years. TGP and [[FGA]] were self-reported using separate scales. Perceived autonomy in participation was assessed with the Impact on Participation and Autonomy Outdoors-subscale, and life-space mobility with the Life-Space Assessment. Two-step cluster analysis was used to create data-driven coping profiles of TGP and [[FGA]]. General linear model analyses showed that the profile including highly tenacious and flexible older people had the highest life-space mobility and perceived autonomy outdoors, whereas the profile including people with low TGP and low [[FGA]] showed the lowest scores. Depressive symptoms attenuated the associations. Active use of both TGP and [[FGA]] is favorable for out-of-home mobility and enables more active participation in society in later life.
|mesh-terms=* Adaptation, Psychological
* Aged
* Aged, 80 and over
* Aging
* Cluster Analysis
* Depression
* Female
* Goals
* Humans
* Independent Living
* Male
* Mobility Limitation
* Surveys and Questionnaires
|keywords=* Aging
* Autonomy
* Coping
* Mobility
* Participation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682663
}}
{{medline-entry
|title=Assimilative and accommodative coping in older adults with and without sensory impairment: four-year change and prospective relations with affective well-being.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30407084
|abstract= Sensory impaired older adults may be particularly dependent on coping strategies such as assimilation (or tenacious goal pursuit [TGP]) and accommodation (or flexible goal adjustment [[[FGA]]]) to secure high levels of well-being. We investigated if late-life changes in these coping strategies and prospective associations of TGP and [[FGA]] with affective well-being vary according to sensory impairment status. Our study sample consisted of 387 adults aged 72-95 years ([i]M[/i] = 82.50 years, SD =4.71 years) who were either visually impaired (VI; [i]n[/i] = 121), hearing impaired (HI; [i]n[/i] = 116), or sensory unimpaired (UI; [i]n[/i] = 150). One hundred sixty-eight individuals were reassessed after approximately 4 years. Both VI and HI revealed a decrease in TGP, whereas TGP remained stable in UI. For [[FGA]], a significant increase in HI was observed, whereas a significant decline emerged in UI. Controlling for age, gender, and cognitive abilities, higher TGP at baseline was significantly associated with higher negative affect 4 years later in VI. Moreover, the positive association between baseline [[FGA]] and subsequent positive affect was stronger in HI than in UI older adults. Our findings suggest that older adults with sensory impairments reveal trajectories of assimilative and accommodative coping and associations of TGP and [[FGA]] with affective well-being that are different from sensory unimpaired individuals.
|mesh-terms=* Adaptation, Psychological
* Aged
* Aged, 80 and over
* Aging
* Case-Control Studies
* Disease Progression
* Female
* Goals
* Humans
* Longitudinal Studies
* Male
* Persons With Hearing Impairments
* Visually Impaired Persons
|keywords=* Tenacious goal pursuit
* affect
* flexible goal adjustment
* hearing impairment
* vision impairment
|full-text-url=https://sci-hub.do/10.1080/13607863.2018.1479833
}}
{{medline-entry
|title=Age stereotypes, flexible goal adjustment, and well-being among Chinese older adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28635315
|abstract=Previous studies have examined the independent roles of positive age stereotypes (PAS) and negative age stereotypes (NAS) in successful aging. This study aimed to examine the joint effect of PAS and NAS on the well-being of Chinese older adults, and to further examine whether this effect was moderated by flexible goal adjustment ([[FGA]]). Using a cross-sectional design, 279 Chinese older adults (age range 60‒97 years) completed measures related to age stereotypes, [[FGA]], and well-being. The results showed that PAS interacted with NAS to predict well-being. In addition, the joint effect of PAS and NAS was moderated by [[FGA]]. Specially, for older adults with low [[FGA]], NAS weakened the positive association between PAS and well-being; whereas, for older adults with high [[FGA]], NAS could not influence the association between PAS and well-being. Tailored interventions to modify aging perceptions and to enhance coping flexibility competence might be helpful for promoting the well-being of older adults.
|mesh-terms=* Aged
* Aged, 80 and over
* Ageism
* Aging
* China
* Cross-Sectional Studies
* Female
* Goals
* Health Knowledge, Attitudes, Practice
* Humans
* Male
* Middle Aged
* Personal Satisfaction
* Social Adjustment
* Stereotyping
|keywords=* Age stereotypes
* flexible goal adjustment
* older adults
* well-being
|full-text-url=https://sci-hub.do/10.1080/13548506.2017.1344253
}}
{{medline-entry
|title=Profiling plasma peptides for the identification of potential ageing biomarkers in Chinese Han adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22802942
|abstract=Advancing age is associated with cardiovascular disease, diabetes mellitus and cancer, and shows significant inter-individual variability. To identify ageing-related biomarkers we performed a proteomic analysis on 1890 Chinese Han individuals, 1136 males and 754 females, aged 18 to 82 years, using weak cation exchange magnetic bead based MALDI-TOF-MS analysis. The study identified 44 peptides which varied in concentration in different age groups. In particular, apolipoprotein A-I (ApoA1) concentration gradually increased between 18 to 50 years of age, the levels of fibrinogen alpha ([[FGA]]) decreased over the same age span, while albumin ([[ALB]]) was significantly degraded in middle-aged individuals. In addition, the plasma peptide profiles of [[FGA]] and four other unidentified proteins were found to be gender-dependent. Plasma proteins such as [[FGA]], [[ALB]] and ApoA1 are significantly correlated with age in the Chinese Han population and could be employed as indicative ageing-related biomarkers.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Apolipoprotein A-I
* Biomarkers
* Female
* Fibrinogen
* Humans
* Male
* Middle Aged
* Peptides
* Serum Albumin
* Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
* Transcriptome

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3389038
}}

FEZ1

2021-05-12T15:36:28Z

OdysseusBot: Новая страница: «Fasciculation and elongation protein zeta-1 (Zygin I) (Zygin-1) ==Publications== {{medline-entry |title=Disruption to schizophrenia-associated gene Fez1 in the...»

Fasciculation and elongation protein zeta-1 (Zygin I) (Zygin-1)

==Publications==

{{medline-entry
|title=Disruption to schizophrenia-associated gene Fez1 in the hippocampus of [[HDAC11]] knockout mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28928414
|abstract=Histone Deacetylase 11 ([[HDAC11]]) is highly expressed in the central nervous system where it has been reported to have roles in neural differentiation. In contrast with previous studies showing nuclear and cytoplasmic localisation, we observed synaptic enrichment of [[HDAC11]]. Knockout mouse models for HDACs 1-9 have been important for guiding the development of isoform specific HDAC inhibitors as effective therapeutics. Given the close relationship between [[HDAC11]] and neural cells in vitro, we examined neural tissue in a previously uncharacterised Hdac11 knockout mouse (Hdac11 ). Loss of [[HDAC11]] had no obvious impact on brain morphology and neural stem/precursor cells isolated from Hdac11 mice had comparable proliferation and differentiation characteristics. However, in differentiating neural cells we observed decreased expression of schizophrenia-associated gene Fez1 (fasciculation and elongation protein zeta 1), a gene previously reported to be regulated by [[HDAC11]] activity. [[FEZ1]] has been associated with the dendritic growth of neurons and risk of schizophrenia via its interaction with [[DISC1]] (disrupted in schizophrenia 1). Examination of cortical, cerebellar and hippocampal tissue reveal decreased Fez1 expression specifically in the hippocampus of adult mice. The results of this study demonstrate that loss of [[HDAC11]] has age dependent and brain-region specific consequences.
|mesh-terms=* Adaptor Proteins, Signal Transducing
* Aging
* Animals
* Cell Line
* Gene Expression Regulation
* Hippocampus
* Histone Deacetylases
* Mice
* Mice, Knockout
* Nerve Tissue Proteins
* Neural Stem Cells
* Neurogenesis
* Schizophrenia

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605701
}}

FES

2021-05-12T15:36:24Z

OdysseusBot: Новая страница: «Tyrosine-protein kinase Fes/Fps (EC 2.7.10.2) (Feline sarcoma/Fujinami avian sarcoma oncogene homolog) (Proto-oncogene c-Fes) (Proto-oncogene c-Fps) (p93c-fes) [F...»

Tyrosine-protein kinase Fes/Fps (EC 2.7.10.2) (Feline sarcoma/Fujinami avian sarcoma oncogene homolog) (Proto-oncogene c-Fes) (Proto-oncogene c-Fps) (p93c-fes) [FPS]

==Publications==

{{medline-entry
|title=An outpatient Tai Chi program: Effects on veterans' functional outcomes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33241873
|abstract=To evaluate the effectiveness of an evidence-based 12-week Tai Chi course designed to improve balance and physical function in a population of older veterans. Community dwelling veterans of all ages with gait and balance problems were invited to participate in the Tai Chi program. Participants completed the Berg Balance Scale (BBS), the Timed Up and Go (TUG) test, and the Falls Efficacy Scale-International ([[FES]]-I) at baseline and again at the end of the program. Descriptive statistics were used to summarize study participants' characteristics. The change from baseline to the end of the 12-week program was calculated for each of the three primary outcome variables (BBS, TUG, [[FES]]-I). Twenty-two veterans, aged 58 years and above, with perceived gait and/or balance issues were enrolled in the program with completion by 11 veterans. Veterans who completed their final assessments showed the BBS, improved significantly (p = 0.004) from baseline to the 12-week assessment. The TUG scores improved by a median of 1.3 s (p = 0.022). There was not a significant change in the [[FES]]-I. Preliminary findings provide evidence of the effectiveness of a 12-week Tai Chi program to improve functional outcomes for older veterans with mild to moderate gait and balance problems.

|keywords=* Tai Chi
* balance
* exercise
* gait
* geriatrics
|full-text-url=https://sci-hub.do/10.1111/nuf.12532
}}
{{medline-entry
|title=Gait Function in Adults Aged 50 Years and Older With Spina Bifida.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33166524
|abstract=To study gait function among individuals with spina bifida (SB) aged 50 years or older. A cross-sectional study conducted in 2017. Home-dwelling participants from all regions in Norway. Individuals between the ages of 51 and 76 years (N=26; 16 women) categorized as independent walkers (n=9), walkers with aids (n=10) and nonwalkers (n=7). Not applicable. Questionnaire, pain assessment, anthropometry, Falls Efficacy Scale International ([[FES]]-I), objective gait analysis, 6-minute walk test (6MWT), and timed Up and Go (TUG). Walking speed correlated with SB severity (ρ=-.59; P=.008). Individuals who walked slower than 0.81 m/s had a higher body mass index (BMI) than those who walked faster (P=.008). Independent walkers walked slower than healthy age-matched walkers (P=.046); spatiotemporal variables showed that this was owing to shorter steps rather than cadence. The mean TUG was 10.6±2.6 seconds in independent walkers and 20.2±6.5 in walkers with aids (P<.01). The mean 6MWT was 504±126 meters in independent walkers and 316±88 in walkers with aids (P<.01). The mean pain intensity (numeric rating scale) was 4.9±2.2 in independent walkers and 4.2±1.6 in walkers with aids, but the difference was not statistically significant. [[FES]]-I was significantly lower among independent walkers (mean, 23.6±3.9) than walkers with aids (mean, 31.4±10.0) (P=.042). Participants commonly experienced an early onset deterioration in gait function, and walking speed was influenced by SB severity and BMI. This highlights the importance of early monitoring and weight management during follow-up for SB.

|keywords=* Adult
* Aging
* Gait analysis
* Myelomeningocele
* Rehabilitation
|full-text-url=https://sci-hub.do/10.1016/j.apmr.2020.10.118
}}
{{medline-entry
|title='Believe the positive' aggregation of fall risk assessment methods reduces the detection of risk of falling in older adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32827945
|abstract=Screening programs for fall prevention in older adults may include several assessment methods. This study investigated the validity of aggregating fall risk assessment methods for stratifying the risk of falling in older adults. This secondary data analysis included 52 community-dwelling residents aged [median (interquartile range)] 74 (69-80) years. Fall occurrences were registered prospectively for six months, with 9 (17%) participants reporting at least one fall during follow-up. The fall risk assessment included the Berg Balance Scale (BBS); polypharmacy (POLY); Falls Risk Assessment Score (FRAS); Fall Risk Assessment Tool (FRAT-up); Falls Efficacy Scale ([[FES]]); and posturography with the Wii Balance Board (WBB). Aggregation of methods' results was performed according to the risk classification ('high risk' or 'low risk') assigned by their respective cut-off values under the 'believe the positive' (BP) strategy. Aggregating 1 (POLY), 2 ( BBS), 3 ( [[FES]]), 4 ( FRAT-up), 5 ( FRAS), and 6 ( BBS) methods resulted in a monotonic decrease of several validity indices including (index [95% confidence interval]) diagnostic odds ratio (10.82 [2.38-54.28] to 0.59 [0.12-2.09]) and accuracy (0.67 [0.54-0.78] to 0.20 [0.11-0.31]). Aggregating fall risk assessment methods-BBS, POLY, FRAS, FRAT-up, [[FES]], WBB-under the BP strategy does not increase the validity of stratification of the risk of falling in older adults.

|keywords=* aging
* creening programs
* elderly health
* rehabilitation
* risks
|full-text-url=https://sci-hub.do/10.1016/j.archger.2020.104228
}}
{{medline-entry
|title=A Single Question as a Screening Tool to Assess Fear of Falling in Young-Old Community-Dwelling Persons.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32165062
|abstract=Fear of falling (FOF) is common in older persons and related to negative outcomes. This study aimed to investigate the relationship between 2 FOF measures: the Falls Efficacy Scale-International ([[FES]]-I) and the single question on FOF and activity restriction (SQ-FAR). Factors associated with disagreement between the 2 measures were further examined. Cross-sectional study. Participants (N = 1359) were community-dwelling persons aged 65 to 70 years who were enrolled in the Lausanne cohort 65 . Data included demographic, functional, cognitive, affective, and health status. FOF was measured with [[FES]]-I and the 3-level SQ-FAR (no FOF, FOF without activity restriction (AR, FOF with AR). [[FES]]-I concern about falling was categorized as low (score 16-19), moderate (score 20-27), and high (score 28-64). Weighted agreement between the [[FES]]-I and the SQ-FAR was 87.8% (Kappa = 0.57). Using the [[FES]]-I as gold standard, the performance of SQ-FAR was good (specificity 86%; sensitivity 74%, negative predicting value 89%, positive predicting value 69%). Among participants with moderate/high FOF according to [[FES]]-I, male sex (P = .011) and the absence of previous falls (P < .001) were associated with disagreement between the 2 tools. Among participants with low FOF, female sex (P = .005), falls history (P < .001), and pre-frailty/frailty status (P = .050) were associated with disagreement. The SQ-FAR has a moderate agreement with [[FES]]-I and might be used as a screening tool. The results also may help design a step-by-step strategy to evaluate and address FOF in the clinical setting.

|keywords=* FES-I
* elderly
* fear of falling
* healthy aging
* older adults
|full-text-url=https://sci-hub.do/10.1016/j.jamda.2020.01.101
}}
{{medline-entry
|title=Fall-related efficacy is a useful and independent index to detect fall risk in Japanese community-dwelling older people: a 1-year longitudinal study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31664911
|abstract=Fall-related efficacy has been found to be associated with both falls and fall risk factors such as physical performance. The aim of the present study was to clarify whether fall-related efficacy is, independent of physical performance and other potential risk factors, associated with future falls in community-dwelling older people. The study participants were 237 Japanese older people aged 65 years and over who were living independently in their community. Fall-related efficacy and physical performance were assessed at baseline using the short version of the Falls Efficacy Scale-International (short [[FES]]-I) and 5-m walking time, the Timed Up and Go Test, the 5 Times Sit to Stand Test, and grip strength. Physical performance was then again assessed at 1-year follow-up. The number of falls was obtained every 6 months for 1 year after the baseline survey. Instrumental activities of daily living (IADL), depression, fall history, current medications, medical history, and pain were also investigated as potential confounding factors that have possible associations with falls. The associations between the short [[FES]]-I, physical performance, and number of falls were analyzed using Poisson regression analysis adjusted for physical performance and potential confounding factors. The mean age of the participants (75.9% women) was 71.1 ± 4.6 years, and 92.8% could perform IADL independently. The total numbers of falls and fallers during the 1-year follow-up period were 70 and 42, respectively. On Poisson regression analysis adjusted for walking time and potential confounding factors, independent of physical performance, the short [[FES]]-I was found to be significantly associated with number of falls (relative risk = 1.09, p < 0.05). On the other hand, physical performance was not significantly associated with the number of falls. The findings of the present study suggest that the short [[FES]]-I, independent of physical performance and other potential risk factors, is a useful index to detect fall risk in community-dwelling older people, and that fall-related efficacy is an important factor in terms of fall prevention.
|mesh-terms=* Accidental Falls
* Activities of Daily Living
* Aged
* Aging
* Female
* Geriatric Assessment
* Humans
* Independent Living
* Japan
* Longitudinal Studies
* Male
* Physical Functional Performance
* Postural Balance
* Risk Factors
* Walking Speed
|keywords=* Accidental falls
* Aged
* Fall-related efficacy
* Japanese
* Physical performance
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820944
}}
{{medline-entry
|title=Investigating Changes in Real-time Conscious Postural Processing by Older Adults during Different Stance Positions Using Electroencephalography Coherence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31514583
|abstract=: Adjustments of posture in response to balance challenges may lead to subsequent increases in conscious posture processing. If cognitive resources are stretched by conscious processing of postural responses fewer resources will be available to attend to environmental trip or fall hazards. The objective of the study was to explore brain activity related to conscious processing of posture as a function of movement specific reinvestment and fear of falling. : Forty-three older adults ([i]M[/i] = 71.4, [i]SD[/i] = 4.1) stood with a wide or narrow stance on a force-plate while neural coherence between verbal-analytical (T3) and motor planning (Fz) regions of the brain was assessed using electroencephalography. The propensity for movement specific reinvestment was assessed using the Chinese version Movement Specific Reinvestment Scale (MSRS-C) and fear of falling was assessed using the Chinese version Fall Efficacy Scale International ([[FES]]-I[CH]). : Scores from the MSRS-C were negatively correlated with changes in T3-Fz coherence that occurred when participants shifted from wide to narrow stance. Together, MSRS-C and [[FES]]-I(CH) uniquely predicted the percentage change in T3-Fz coherence between the two stance conditions. : Presented with two postural tasks of different complexities, participants with a lower propensity for conscious control of their movements (movement specific reinvestment) exhibited larger changes in real-time brain activity (neural coherence) associated with conscious postural processing.
|mesh-terms=* Accidental Falls
* Aged
* Aging
* Brain
* Electroencephalography
* Fear
* Female
* Humans
* Male
* Movement
* Postural Balance
* Posture

|full-text-url=https://sci-hub.do/10.1080/0361073X.2019.1664450
}}
{{medline-entry
|title=Effectiveness of Daily Use of Bilateral Custom-Made Ankle-Foot Orthoses on Balance, Fear of Falling, and Physical Activity in Older Adults: A Randomized Controlled Trial.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30504728
|abstract=Foot problems are prevalent in older adults, which may increase the risk and concern for falls. Ankle-foot orthoses (AFO) have been shown to be effective in the stabilization of lower extremities, but their long-term effectiveness in improving balance and their potential to encourage older adults to become more physically active are still debated. This randomized controlled trial investigated the effectiveness of daily use of a custom-made AFO on balance, fear of falling, and physical activity in older adults. Forty-four older adults with concern about or at risk for falling were randomly allocated to either the control group (CG; 77.3% female, age 75.6 ± 6.5 years, BMI 29.3 ± 6.4) or the intervention group (IG; 63.6% female, age 73.7 ± 6.3 years, BMI = 27.8 ± 4.8). The IG received walking shoes and bilateral custom-made AFO. The CG received only walking shoes. At the baseline and 6-month follow-ups, balance and physical activity were assessed using validated wearable instrumentation and fear of falling was assessed using the Fall Efficacy Scale-International ([[FES]]-I). Adherence and acceptability toward wearing the AFO were assessed using self-reported questionnaires at the 6-month follow-up. No significant between-group difference was observed at baseline (p = 0.144-0.882). Compared to baseline and the CG, hip, ankle, and center-of-mass (COM) sways were significantly reduced at the 6-month follow-up in the IG while standing with the feet together during the eyes-open condition (p = 0.005-0.040). Within the IG, the [[FES]]-I was reduced significantly (p = 0.036) and there was an increasing trend in the number of walking bouts with a medium effect size (d = 0.52, p = 0.440) compared to baseline. However, there were no significant changes in [[FES]]-I and physical activity measures in the CG (p = 0.122-0.894). The reduction in COM sway in the IG was moderately correlated with adherence (r = -0.484, p = 0.047) and strongly correlated with baseline COM sway (r = -0.903, p < 0.001). Results suggest that bilateral custom-made AFO plus walking shoes is effective in improving balance compared to walking shoes alone, and it significantly reduces the fear of falling, with a nonsignificant but noticeable positive trend in physical activity, compared to baseline. The results also suggest that older adults with poor balance at baseline and higher daily adherence to using the AFO will gain more benefit from the AFO intervention.
|mesh-terms=* Accidental Falls
* Aged
* Aged, 80 and over
* Ankle Joint
* Exercise
* Fear
* Female
* Foot
* Foot Orthoses
* Geriatrics
* Humans
* Male
* Patient Compliance
* Patient Satisfaction
* Postural Balance
* Shoes
* Treatment Outcome
* Walking
|keywords=* Ankle-foot orthoses
* Balance
* Fear of falling
* Older adults
* Physical activity
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530116
}}
{{medline-entry
|title=Decline in sensorimotor systems explains reduced falls self-efficacy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30015133
|abstract=Physical performance including balance tasks is one of the main factors explaining the variance in falls self-efficacy in older adults. Balance performance is often measured by use of gross assessment scales, which assess the result of integration of all systems involved in postural control. We aimed to investigate which measurements of postural control correlate to falls self-efficacy scores as measured by the [[FES]]-I instrument, and which sensory and motor systems best explain them. A cross sectional study was designed, in which 45 older adults performed quiet stance and limits of stability trials during which their center of pressure (CoP) excursion was recorded. Falls self-efficacy was measured using the Falls Efficacy Scale - International. Eyesight, vestibular function, proprioception, reaction time and strength were also measured. Hierarchical orthogonal projection of latent structures was used to model [[FES]]-I with the CoP trials and then with the sensory and muscle function data. Fes-I could be explained to 39%, with the eyes open trials and the limits of stability trials loading the heaviest. The base model could be explained to 40% using the sensory and muscle function data, with lower limb strength, leg proprioception, neck proprioception, reaction time and eyesight loading the heaviest.
|mesh-terms=* Accidental Falls
* Aged
* Aged, 80 and over
* Aging
* Female
* Humans
* Male
* Muscle, Skeletal
* Postural Balance
* Proprioception
* Self Efficacy
|keywords=* Aging
* Fear
* Postural balance
* Posture
* Self efficacy
|full-text-url=https://sci-hub.do/10.1016/j.jelekin.2018.07.001
}}
{{medline-entry
|title=Fear of Falling in Older Adults with Diabetes Mellitus: The IMIAS Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29956644
|abstract=ABSTRACTSeveral determinants of developing fear of falling (FoF) overlap with the consequences of diabetes mellitus (DM). We compared the prevalence and severity of FoF in older adults with and without DM and identified which FoF determinants contribute to FoF severity in older adults with DM. We used Canadian baseline data from the International Mobility in Aging Study (IMIAS) which identified 141 older adults with DM (DM-group;age:68.88±2.80years) and 620 without DM (noDM-group;age:68.81±2.68years). FoF was quantified with Falls Efficacy Scale-International ([[FES]]-I). FoF determinants were evaluated in demographic/health-related, physical, psychological, and social domains. High concern of FoF was more prevalent and of higher severity in 10/16 [[FES]]-I activities in the DM-group compared to the noDM-group. Higher FoF severity in the DM-group was associated with poor physical performance, being female, fall history, and clinical depressive symptoms. Protocols developed for screening and interventions may reduce FoF severity in this population.
|mesh-terms=* Accidental Falls
* Aged
* Case-Control Studies
* Cross-Sectional Studies
* Depression
* Diabetes Mellitus
* Fear
* Female
* Geriatric Assessment
* Humans
* Independent Living
* Longitudinal Studies
* Male
* Mobility Limitation
* Quality of Life
* Severity of Illness Index
* Social Support
|keywords=* aging
* chutes
* diabetes mellitus
* diabète de type 2
* falls
* fear of falling
* peur de chuter
* vieillissement
|full-text-url=https://sci-hub.do/10.1017/S071498081800020X
}}
{{medline-entry
|title=Cross-cultural adaptation and measurement properties testing of the Iconographical Falls Efficacy Scale (Icon-[[FES]]).
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29486980
|abstract=The Iconographical Falls Efficacy Scale (Icon-[[FES]]) is an innovative tool to assess concern of falling that uses pictures as visual cues to provide more complete environmental contexts. Advantages of Icon-[[FES]] over previous scales include the addition of more demanding balance-related activities, ability to assess concern about falling in highly functioning older people, and its normal distribution. To perform a cross-cultural adaptation and to assess the measurement properties of the 30-item and 10-item Icon-[[FES]] in a community-dwelling Brazilian older population. The cross-cultural adaptation followed the recommendations of international guidelines. We evaluated the measurement properties (i.e. internal consistency, test-retest reproducibility, standard error of the measurement, minimal detectable change, construct validity, ceiling/floor effect, data distribution and discriminative validity), in 100 community-dwelling people aged ≥60 years. The 30-item and 10-item Icon-[[FES]]-Brazil showed good internal consistency (alpha and omega >0.70) and excellent intra-rater reproducibility (ICC =0.96 and 0.93, respectively). According to the standard error of the measurement and minimal detectable change, the magnitude of change needed to exceed the measurement error and variability were 7.2 and 3.4 points for the 30-item and 10-item Icon-[[FES]], respectively. We observed an excellent correlation between both versions of the Icon-[[FES]] and Falls Efficacy Scale - International (rho=0.83, p<0.001 [30-item version]; 0.76, p<0.001 [10-item version]). Icon-[[FES]] versions showed normal distribution, no floor/ceiling effects and were able to discriminate between groups relating to fall risk factors. Icon-[[FES]]-Brazil is a semantically and linguistically appropriate tool with acceptable measurement properties to evaluate concern about falling among the community-dwelling older population.
|mesh-terms=* Accidental Falls
* Brazil
* Cross-Cultural Comparison
* Humans
* Independent Living
* Reproducibility of Results
* Risk Factors
|keywords=* Accidental falls
* Aging
* Fear of falling
* Measurement properties
* Older people
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095044
}}
{{medline-entry
|title=Binocular Vision Disorders and Visual Attention: Associations With Balance and Mobility in Older Adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28714802
|abstract=Understanding which aspects of vision are related to falls is important. We examine the associations between tests of balance, mobility, fear of falling ([[FES]]-1) and aspects of vision in 72 adults aged 70 . Balance and mobility were examined using the One Legged Stance test (OLST), the Sit to Stand test (STST) and the 5 Meter Walking test (5MWT). Visual measures included visual acuity (VA), contrast sensitivity, stereoacuity, binocular vision (BV) measurements, Useful field of View (UFV) and Attended Field of View (AFOV). Reduced performance on the OLST and the STST was significantly correlated with abnormal BV and poorer intermediate VA. Poorer function on the 5MWT and the [[FES]]-I was also predicted by poor intermediate VA and poorer performance on the OLST, STST and the 5MWT was associated with UFV errors. The results are of high importance as many BV disorders are treatable and visual attention is trainable.
|mesh-terms=* Accidental Falls
* Aged
* Aged, 80 and over
* Contrast Sensitivity
* Female
* Humans
* Male
* Postural Balance
* Vision Disorders
* Vision, Binocular
* Visual Acuity
|keywords=* aging
* falls
* geriatric
* vision
|full-text-url=https://sci-hub.do/10.1123/japa.2016-0349
}}
{{medline-entry
|title=Genome-wide methylation analysis reveals differentially methylated loci that are associated with an age-dependent increase in bovine fibroblast response to LPS.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28545453
|abstract=Differences in DNA methylation are known to contribute to the development of immune-related disorders in humans but relatively little is known about how methylation regulates immune function in cattle. Utilizing whole-transcriptome analyses of bovine dermal fibroblasts, we have previously identified an age and breed-dependent up-regulation of genes within the toll-like receptor 4 (TLR4) pathway that correlates with enhanced fibroblast production of IL-8 in response to lipopolysaccharide (LPS). Age-dependent differences in IL-8 production are abolished by treatment with 5-aza-2-deoxycytidine and Trichostatin A (AZA-TSA), suggesting epigenetic regulation of the innate response to LPS. In the current study, we performed reduced representation bisulfite sequencing (RRBS) on fibroblast cultures isolated from the same animals at 5- and 16-months of age to identify genes that exhibit variable methylation with age. To validate the role of methylation in gene expression, six innate response genes that were hyper-methylated in young animals were assessed by RT-qPCR in fibroblasts from animals at different ages and from different breeds. We identified 14,094 differentially methylated CpGs (DMCs) that differed between fibroblast cultures at 5- versus 16-months of age. Of the 5065 DMCs that fell within gene regions, 1117 were located within promoters, 1057 were within gene exons and 2891 were within gene introns and 67% were more methylated in young cultures. Transcription factor enrichment of the promoter regions hyper-methylated in young cultures revealed significant regulation by the key pro-inflammatory regulator, NF-κB. Additionally, five out of six chosen genes (PIK3R1, [[FES]], [[NFATC1]], [[TNFSF13]] and RORA) that were more methylated in young cultures showed a significant reduction in expression post-LPS treatment in comparison with older cultures. Two of these genes, [[FES]] and [[NFATC1]], were similarly down-regulated in Angus cultures that also exhibit a low LPS response phenotype. Our study has identified immune-related loci regulated by DNA methylation in cattle that may contribute to differential cellular response to LPS, two of which exhibit an identical expression profile in both low-responding age and breed phenotypes. Methylation biomarkers of differential immunity may prove useful in developing selection strategies for replacement cows that are less susceptible to severe infections, such as coliform mastitis.
|mesh-terms=* Aging
* Animals
* Cattle
* DNA Methylation
* Epigenesis, Genetic
* Fibroblasts
* Genetic Loci
* Genomics
* Interleukin-6
* Interleukin-8
* Lipopolysaccharides
* Transcriptome
|keywords=* DNA Methylation
* Inflammation
* Innate Immunity
* LPS
* RRBS
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445414
}}
{{medline-entry
|title=[[FES]] in Europe and Beyond: Current Translational Research.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28078074
|abstract=Capacity of adult neural and muscle tissues to respond to external Electrical Stimulation (ES) is the biological basis for the development and implementation of mobility impairment physiotherapy protocols and of related assistive technologies, e.g, Functional Electrical Stimulation ([[FES]]). All body tissues, however, respond to electrical stimulation and, indeed, the most successful application of [[FES]] is electrical stimulation of the heart to revert or limit effects of arrhythmias (Pace-makers and Defibrillators). Here, we list and discuss results of [[FES]] current research activities, in particular those presented at 2016 Meetings: the PaduaMuscleDays, the Italian Institute of Myology Meeting, the 20 International Functional Electrical Stimulation Society (I[[FES]]S) conference held in Montpellier and the Vienna Workshop on [[FES]]. Several papers were recently e-published in the European Journal of Translational Myology as reports of meeting presentations. All the events and publications clearly show that [[FES]] research in Europe and beyond is alive and promisses translation of results into clinical management of a very large population of persons with deficiencies.

|keywords=* FES
* aging
* biomedical technology
* denervated muscle
* mobility impairment
* prevention and assistive technology
* rehabilitation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220221
}}
{{medline-entry
|title=Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28078066
|abstract=Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation ([[FES]]) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active, i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of [[FES]] and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging. ClinicalTrials.gov: NCT01679977.

|keywords=* aging
* co-expression of fast and slow myosin heavy chains
* fiber type grouping
* human skeletal muscle
* lifelong physical exercise denervation and reinnervation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220213
}}
{{medline-entry
|title=Recovery from muscle weakness by exercise and [[FES]]: lessons from Masters, active or sedentary seniors and SCI patients.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27592133
|abstract=Many factors contribute to the decline of skeletal muscle that occurs as we age. This is a reality that we may combat, but not prevent because it is written into our genome. The series of records from World Master Athletes reveals that skeletal muscle power begins to decline at the age of 30 years and continues, almost linearly, to zero at the age of 110 years. Here we discuss evidence that denervation contributes to the atrophy and slowness of aged muscle. We compared muscle from lifelong active seniors to that of sedentary elderly people and found that the sportsmen have more muscle bulk and slow fiber type groupings, providing evidence that physical activity maintains slow motoneurons which reinnervate muscle fibers. Further, accelerated muscle atrophy/degeneration occurs with irreversible Conus and Cauda Equina syndrome, a spinal cord injury in which the human leg muscles may be permanently disconnected from the nervous system with complete loss of muscle fibers within 5-8 years. We used histological morphometry and Muscle Color Computed Tomography to evaluate muscle from these peculiar persons and reveal that contraction produced by home-based Functional Electrical Stimulation (h-b[[FES]]) recovers muscle size and function which is reversed if h-b[[FES]] is discontinued. [[FES]] also reverses muscle atrophy in sedentary seniors and modulates mitochondria in horse muscles. All together these observations indicate that [[FES]] modifies muscle fibers by increasing contractions per day. Thus, [[FES]] should be considered in critical care units, rehabilitation centers and nursing facilities when patients are unable or reluctant to exercise.
|mesh-terms=* Age Factors
* Aged
* Aging
* Animals
* Cauda Equina
* Electric Stimulation
* Electric Stimulation Therapy
* Exercise
* Horses
* Humans
* Muscle Fibers, Skeletal
* Muscle Weakness
* Muscle, Skeletal
* Muscular Atrophy
* Spinal Cord Injuries
|keywords=* Aging
* Denervation and type grouping
* FES recovery
* Master Athletes
* Muscle
* Muscle Color Computed Tomography
|full-text-url=https://sci-hub.do/10.1007/s40520-016-0619-1
}}
{{medline-entry
|title=Biology of Muscle Atrophy and of its Recovery by [[FES]] in Aging and Mobility Impairments: Roots and By-Products.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26913160
|abstract=There is something in our genome that dictates life expectancy and there is nothing that can be done to avoid this; indeed, there is not yet any record of a person who has cheated death. Our physical prowess can vacillate substantially in our lifetime according to our activity levels and nutritional status and we may fight aging, but we will inevitably lose. We have presented strong evidence that the atrophy which accompanies aging is to some extent caused by loss of innervation. We compared muscle biopsies of sedentary seniors to those of life long active seniors, and show that these groups indeed have a different distribution of muscle fiber diameter and fiber type. The senior sportsmen have many more slow fiber-type groupings than the sedentary people which provides strong evidence of denervation-reinnervation events in muscle fibers. It appears that activity maintains the motoneurons and the muscle fibers. Premature or accelerated aging of muscle may occur as the result of many chronic diseases. One extreme case is provided by irreversible damage of the Conus and Cauda Equina, a spinal cord injury (SCI) sequela in which the human leg muscles may be completely and permanently disconnected from the nervous system with the almost complete disappearance of muscle fibers within 3-5 years from SCI. In cases of this extreme example of muscle degeneration, we have used 2D Muscle Color CT to gather data supporting the idea that electrical stimulation of denervated muscles can retain and even regain muscle. We show here that, if people are compliant, atrophy can be reversed. A further example of activity-related muscle adaptation is provided by the fact that mitochondrial distribution and density are significantly changed by functional electrical stimulation in horse muscle biopsies relative to those not receiving treatment. All together, the data indicate that [[FES]] is a good way to modify behaviors of muscle fibers by increasing the contraction load per day. Indeed, it should be possible to defer the muscle decline that occurs in aging people and in those who have become unable to participate in physical activities. Thus, [[FES]] should be considered for use in rehabilitation centers, nursing facilities and in critical care units when patients are completely inactive even for short periods of time.

|keywords=* Muscle power
* aging decay
* equine muscle spasm
* h-b FES-induced muscle recovery
* long-term denervated muscles
* master athletes
* muscle denervation/reinnervation
* subsarcolemmal mitochondria
* type groupings
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748978
}}
{{medline-entry
|title=Balance Disorders in the Elderly: Does Instability Increase Over Time?
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26848036
|abstract=To analyze the equilibriometric differences between 2 populations of elderly patients (young elderly and very elderly) with instability induced solely by age. Cross-sectional study, with 2 study groups classified according to patient age (cut-points in twenty-fifth and seventy-fifth percentiles of the age of the sample). 64 patients aged 65 years or more. Two groups of 32 subjects were established: group A (people 65 years of age or older but less than 72.6, twenty-fifth percentile) and group B (patients 82.5 years, seventh-fifth percentile, or older). Main analyzed variables: timed up-and-go test, sensory organization test of the computerized dynamic posturography, Dizziness Handicap Inventory (DHI), and Short Falls Efficacy Scale-International ([[FES]]-I) questionnaires. Student's t test or the Mann-Whitney test were used. The older patients obtain poorer scores in the equilibriometric tests but not in all of them. In the sensory organization test, the older patients make poorer use of visual and vestibular information; they also require more time and steps for the timed up-and-go. With regards to the questionnaires, fear of falling is greater (higher Short [[FES]]-I scores) but not subjective perception of disability (DHI scores without differences). There is a need to establish aged subgroups of elderly patients with instability, adapting therapeutic strategies.
|mesh-terms=* Accidental Falls
* Age Factors
* Aged
* Aged, 80 and over
* Aging
* Cross-Sectional Studies
* Dizziness
* Female
* Humans
* Male
* Postural Balance
* Sensation Disorders
* Surveys and Questionnaires
* Vestibular Diseases
|keywords=* DHI
* computerized dynamic posturography
* elderly
* fall
* instability
|full-text-url=https://sci-hub.do/10.1177/0003489416629979
}}
{{medline-entry
|title=Age group classification and gender detection based on forced expiratory spirometry.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26736321
|abstract=This paper investigates the utility of forced expiratory spirometry ([[FES]]) test with efficient machine learning algorithms for the purpose of gender detection and age group classification. The proposed method has three main stages: feature extraction, training of the models and detection. In the first stage, some features are extracted from volume-time curve and expiratory flow-volume loop obtained from [[FES]] test. In the second stage, the probabilistic models for each gender and age group are constructed by training Gaussian mixture models (GMMs) and Support vector machine (SVM) algorithm. In the final stage, the gender (or age group) of test subject is estimated by using the trained GMM (or SVM) model. Experiments have been evaluated on a large database from 4571 subjects. The experimental results show that average correct classification rate performance of both GMM and SVM methods based on the [[FES]] test is more than 99.3 % and 96.8 % for gender and age group classification, respectively.
|mesh-terms=* Aging
* Algorithms
* Exhalation
* Humans
* Models, Statistical
* Normal Distribution
* Sex Characteristics
* Spirometry
* Support Vector Machine

|full-text-url=https://sci-hub.do/10.1109/EMBC.2015.7318421
}}
{{medline-entry
|title=Is there a relationship between short [[FES]]-I test scores and objective assessment of balance in the older people with age-induced instability?
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26412554
|abstract=Fear of falling (FOF) is a common problem among the elderly. The purpose of this study is to evaluate whether there is a correlation between FOF, estimated via the short [[FES]]-I test, and objective evaluation of balance in a group of elderly patients with age-related instability. The balance of 139 subjects of more than 65 years of age is evaluated by the timed up and go test and the computerised dynamic posturography (CDP). Different groups of elderly patients were established according to the number of falls in the previous 12 months, and the correlation with short [[FES]]-I test scores was evaluated. Based on the results, ROC curves were calculated. The short [[FES]]-I test presents a good capacity to distinguish between subjects with ≤ 3 falls/year and subjects with ≥ 4 falls/year (AUC 0.719, 95%CI 0.627-0.810). A test score of 14.5 is the best cut-off point (74% sensitivity, 51% specificity). Using this cut-off point, the study sample comprises two groups: subjects with test scores of 7-14 vs 15-28, with the first group obtaining best results with statistical significance (Student's t-test and the Mann-Whitney test) in most of the balance tests. The short [[FES]]-I is an excellent instrument that measures FOF in the elderly, and it is correlated with their number of falls both in real life and on the CDP. It is simple and fast, and so can be considered an extraordinary screening test relative to real risk of falls in the elderly.
|mesh-terms=* Accidental Falls
* Aged
* Aged, 80 and over
* Aging
* Fear
* Female
* Geriatric Assessment
* Humans
* Male
* Postural Balance
* Psychometrics
* Reproducibility of Results
* Sensitivity and Specificity
|keywords=* Computerised dynamic posturography
* Fear of falling
* Instability
* Older people
* Short FES-I
|full-text-url=https://sci-hub.do/10.1016/j.archger.2015.09.005
}}
{{medline-entry
|title=Age-associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26194491
|abstract=This 3-year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of life. Our findings reinforce the importance of preserving muscle health with advancing age. The age-associated loss of skeletal muscle quantity and function are critical determinants of independent physical functioning in later life. Longitudinal studies investigating how decrements in muscle components of sarcopenia impact fear of falling (FoF) and quality of life (QoL) in older adults are lacking. Twenty-six healthy older subjects (age, 74.1 ± 3.7; Short Physical Performance Battery (SPPB) score ≥10) and 22 mobility-limited older subjects (age, 77.2 ± 4.4; SPPB score ≤9) underwent evaluations of lower extremity muscle size and composition by computed tomography, strength and power, and physical performance at baseline and after 3-year follow-up. The Falls Efficacy Scale ([[FES]]) and Short Form-36 questionnaire (SF-36) were also administered at both timepoints to assess FoF and QoL, respectively. At 3-year follow-up, muscle cross-sectional area (CSA) (p < 0.013) and power decreased (p < 0.001), while intermuscular fat infiltration increased (p < 0.001). These decrements were accompanied with a longer time to complete 400 m by 22 ± 46 s (p < 0.002). Using linear mixed-effects regression models, declines of muscle CSA, strength and power, and SPPB score were associated with increased [[FES]] score (p < 0.05 for each model). Reduced physical component summary score of SF-36 over follow-up was independently associated with decreased SPPB score (p < 0.020), muscle CSA (p < 0.046), and increased 400 m walk time (p < 0.003). In older adults with and without mobility limitations, declining muscle mass, strength, power, and physical performance contribute independently to increase FoF, while declines of muscle mass and physical performance contribute to deterioration of QoL. These findings provide further rationale for developing interventions to improve aging muscle health.
|mesh-terms=* Accidental Falls
* Aged
* Aged, 80 and over
* Aging
* Case-Control Studies
* Exercise Test
* Fear
* Female
* Follow-Up Studies
* Geriatric Assessment
* Humans
* Male
* Mobility Limitation
* Motor Activity
* Muscle Strength
* Muscle, Skeletal
* Prospective Studies
* Psychometrics
* Quality of Life
|keywords=* Aging
* Fear of falling
* Muscle
* Physical functioning
* Quality of life
* Sarcopenia
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960453
}}
{{medline-entry
|title=Effects of functional electric stimulation cycle ergometry training on lower limb musculature in acute sci individuals.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24453530
|abstract=The purpose of this study was to compare three different intervals for a between sets rest period during a common isokinetic knee extension strength-testing protocol of twenty older Brazilian men (66.30 ± 3.92 yrs). The volunteers underwent unilateral knee extension (Biodex System 3) testing to determine their individual isokinetic peak torque at 60, 90, and 120° ·s-1. The contraction speeds and the rest periods between sets (30, 60 and 90 s) were randomly performed in three different days with a minimum rest period of 48 hours. Significant differences between and within sets were analyzed using a One Way Analysis of Variance (ANOVA) with repeated measures. Although, at angular velocity of 60°·s-1 produced a higher peak torque, there were no significant differences in peak torque among any of the rest periods. Likewise, there were no significant differences between mean peak torque among all resting periods (30, 60 and 90s) at angular velocities of 90 and 120°·s-1. The results showed that during a common isokinetic strength testing protocol a between set rest period of at least 30 s is sufficient for recovery before the next test set in older men. Key PointsMuscle fiber cross sectional area (CSAf ) decreased 38% following spinal cord injury (SCI).Early intervention with functional electric stimulation cycle ergometry ([[FES]]-CE) prevented further loss of CSAf in SCI patients and increased power output.Muscle myosin heavy chain (MHC) and myonuclear density were unaffected by SCI or [[FES]]-CE.

|keywords=* Aging
* isokinetic test
* muscle fatigue
* muscle strength
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887329
}}
{{medline-entry
|title=Concern about falling in older women with a history of falls: associations with health, functional ability, physical activity and quality of life.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24107382
|abstract=Fear of falling has been linked to activity restriction, functional decline, decreased quality of life and increased risk of falling. Factors that distinguish persons with a high concern about falling from those with low concern have not been systematically studied. This study aimed to expose potential health-related, functional and psychosocial factors that correlate with fear of falling among independently living older women who had fallen in the past year. Baseline data of 409 women aged 70-80 years recruited to a randomised falls prevention trial (DEX) (NCT00986466) were used. Participants were classified according to their level of concern about falling using the Falls Efficacy Scale International ([[FES]]-I). Multinomial logistic regression analyses were performed to explore associations between health-related variables, functional performance tests, amount of physical activity, quality of life and [[FES]]-I scores. 68% of the participants reported a moderate to high concern ([[FES]]-I ≥ 20) about falls. Multinomial logistic regression showed that highly concerned women were significantly more likely to have poorer health and quality of life and lower functional ability. Reported difficulties in instrumental activities of daily living, balance, outdoor mobility and poorer quality of life contributed independently to a greater concern about falling. Concern about falling was highly prevalent in our sample of community-living older women. In particular, poor perceived general health and mobility constraints contributed independently to the difference between high and low concern of falling. Knowledge of these associations may help in developing interventions to reduce fear of falling and activity avoidance in old age.
|mesh-terms=* Accidental Falls
* Activities of Daily Living
* Aged
* Aged, 80 and over
* Aging
* Fear
* Female
* Finland
* Health Status
* Humans
* Independent Living
* Logistic Models
* Motor Activity
* Quality of Life
* Risk Factors
* Surveys and Questionnaires

|full-text-url=https://sci-hub.do/10.1159/000354335
}}
{{medline-entry
|title=Which factors are associated with fear of falling in community-dwelling older people?
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24100619
|abstract=fear of falling (FOF) is common in older people and associated with serious physical and psychosocial consequences. Identifying those at risk of FOF can help target interventions to both prevent falls and reduce FOF. to identify factors associated with FOF. cross-sectional study in 1,088 community-dwelling older people aged ≥65 years. data were collected on socio-demographic characteristics, self-perceived health, exercise, risk factors for falls, FOF (Short [[FES]]-I), and functional measures. Logistic regression models of increasing complexity identified factors associated with FOF. high FOF (Short [[FES]]-I ≥11) was reported by 19%. A simpler model (socio-demographic falls risk factors) correctly classified as many observations (82%) as a more complex model (socio-demographic falls risk factors functional measures) with similar sensitivity and specificity values in both models. There were significantly raised odds of FOF in the simpler model with the following factors: unable to rise from a chair of knee height (OR: 7.39), lower household income (OR: 4.58), using a walking aid (OR: 4.32), difficulty in using public transport (OR: 4.02), poorer physical health (OR: 2.85), black/minority ethnic group (OR: 2.42), self-reported balance problems (OR: 2.17), lower educational level (OR: 2.01) and a higher BMI (OR: 1.06). a range of factors identify those with FOF. A simpler model performs as well as a more complex model containing functional assessments and could be used in primary care to identify those at risk of FOF, who could benefit from falls prevention interventions.
|mesh-terms=* Accidental Falls
* Age Factors
* Aged
* Aged, 80 and over
* Aging
* Cross-Sectional Studies
* England
* Fear
* Female
* Geriatric Assessment
* Humans
* Independent Living
* Logistic Models
* Male
* Multivariate Analysis
* Odds Ratio
* Risk Factors
|keywords=* elderly
* falling
* fear of falling
* older people
* older persons
* risk factors
|full-text-url=https://sci-hub.do/10.1093/ageing/aft154
}}
{{medline-entry
|title=The effects of aging and electrical stimulation exercise on bone after spinal cord injury.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23730530
|abstract=Age related bone loss predisposes adults to osteoporosis. This is especially true for individuals with spinal cord injury (SCI). The effects of decreased bone loading with older age and paralysis significantly contribute to decreased bone mass and increased risk for fragility fractures. Loading bone via volitional muscle contractions or by using electrical stimulation are common methods for helping to prevent and/or decrease bone loss. However the effectiveness and safety of electrical stimulation activities remain unclear. The purpose of this review is to investigate the factors associated with aging and osteoporosis after SCI, the accuracy of bone measurement, the effects of various forms of bone loading activities with a focus on electrical stimulation activities and the safety of physical exercise with a focus on electrical stimulation cycling. Osteoporosis remains a disabling and costly condition for older adults and for those with paralysis. Both dual energy x-ray absorptiometry and peripheral quantitative computed tomography are valuable techniques for measuring bone mineral density (BMD) with the latter having the ability to differentiate trabecular and cortical bone. Physical activities have shown to be beneficial for increasing BMD however, the extent of the benefits related to aging and paralysis remain undetermined. Electrical stimulation activities administered appropriately are assumed safe due to thousands of documented safe [[FES]] cycling sessions. However, specific documentation is needed to verify safety and to development formal guidelines for optimal use.

|keywords=* aging
* bone mineral density
* electrical stimulation exercise
* osteoporosis
* spinal cord injury
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660124
}}
{{medline-entry
|title=Validation of the Iconographical Falls Efficacy Scale in cognitively impaired older people.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23682158
|abstract=This study evaluated psychometric properties of the Iconographical Falls Efficacy Scale (Icon-[[FES]]) to measure fear of falling in cognitively impaired older people. Icon-[[FES]] uses pictures as visual cues to prompt responses. A total of 50 community-dwelling older people with moderate cognitive impairment were assessed on Icon-[[FES]], Falls Efficacy Scale-International, and various physical and cognitive measures. Overall structure and measurement properties of Icon-[[FES]], as evaluated with item response theory, were good. Internal consistency was high (Cronbach's alpha = 0.97). Distribution was near normal, indicating absence of floor and ceiling effects. Icon-[[FES]] construct validity was supported by its relation with Falls Efficacy Scale-International (r = .68, p < .001) and its ability to discriminate between groups relating to fall risk factors (gender, balance, falls). Scores were not affected by different levels of cognitive functioning, as assessed with the Mini-Mental State Examination and Trail Making Test. Icon-[[FES]] is the first measure of fear of falling that compensates for reduced abstract abilities by using pictures to match the verbal descriptions. This study supports its feasibility, reliability, and validity to assess fear of falling in people with moderate cognitive impairment or dementia living in the community. Compared with Falls Efficacy Scale-International, Icon-[[FES]] was better at identifying participants with higher fall risk and did not show a floor effect likely due to a greater range of physically challenging activities.
|mesh-terms=* Accidental Falls
* Aged
* Aged, 80 and over
* Aging
* Cognitive Dysfunction
* Cohort Studies
* Fear
* Female
* Humans
* Male
* Psychometrics
* Reproducibility of Results
* Risk Factors
|keywords=* Alzheimer’s disease
* Dementia
* Falls
* Fear of falling
* Geriatric assessment
|full-text-url=https://sci-hub.do/10.1093/gerona/glt007
}}
{{medline-entry
|title=[A qualitative study of Falls Efficacy Scale-International/Hips. What do we measure?].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23397435
|abstract=Pilot-testing a new instrument: the Falls Efficacy Scale-International/Hips ([[FES]]-I/Hips). This instrument is intended to measure 'Fear of Falling' (FoF). To the current instrument, the Falls Efficacy Scale-International, are four questions added for patients who are rehabilitating in a nursing home. It is pretested and used in the HIPS-study. Qualitative exploratory study with interviews in a Three Step Test Interview (TSTI) protocol. Respondents (N = 12) were asked to think aloud while completing the questionnaire. The instruction how to complete the questionnaire is well understood by patients but was not properly used by them. The questionnaire contains questions with difficult words and questions which are no longer relevant. There are six "two-in-one questions" that cause confusion. Use of the standard instruction when completing the [[FES]]-I/Hips can lead to underreporting of FoF. Adaptation of certain items may improve content validity. Further psychometric studies are recommended to determine whether the proposed adjustments are appropriate.
|mesh-terms=* Accidental Falls
* Aged
* Aged, 80 and over
* Aging
* Fear
* Female
* Hip Fractures
* Humans
* Male
* Nursing Homes
* Pilot Projects
* Psychometrics
* Surveys and Questionnaires

|full-text-url=https://sci-hub.do/10.1007/s12439-013-0005-9
}}
{{medline-entry
|title=The Baby Boomers' intergenerational relationships.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22250130
|abstract=As Baby Boomers enter late life, relationships with family members gain importance. This review article highlights two aspects of their intergenerational relationships: (a) caregiving for aging parents and (b) interactions with adult children in the context of changing marital dynamics. The researchers describe three studies: (a) the Within Family Differences Study (WFDS) of mothers aged 65-75 and their multiple grown children (primarily Baby Boomers) ongoing since 2001; (b) the Family Exchanges Study ([[FES]]) of Baby Boomers aged 42-60, their spouses, parents, and multiple grown children ongoing since 2008; and (c) the Longitudinal Study of Generations (LSoG) of 351 three-generation families started when the Baby Boomers were teenagers in 1971, with interviews every 3-5 years from 1985 to 2005. These studies show that the Baby Boomers in midlife navigate complex intergenerational patterns. The WFDS finds aging parents differentiate among Baby Boomer children in midlife, favoring some more than others. The [[FES]] shows that the Baby Boomers are typically more involved with their children than with their aging parents; Boomers' personal values, family members' needs, and personal rewards shape decisions about support. The LSoG documents how divorce and remarriage dampen intergenerational obligations in some families. Moreover, loosening cultural norms have weakened family bonds in general. Reviews of these studies provide insights into how the Baby Boomers may negotiate caregiving for aging parents as well as the likelihood of family care they will receive when their own health declines in the future.
|mesh-terms=* Adult Children
* Aging
* Caregivers
* Female
* Humans
* Intergenerational Relations
* Male
* Parent-Child Relations
* Parenting
* Parents
* Population Growth
* Social Support

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304890
}}
{{medline-entry
|title=Effects of fear of falling on muscular coactivation during walking.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21606665
|abstract=Increased fear of falling is associated with greater muscular coactivation during standing postural control. Excessive muscular coactivation reduces the performance of agonist muscles. Although several recent studies have observed increased muscular coactivation during walking in older adults, little is known about the relationship between fear of falling and muscular coactivation during walking. The purpose of this study was to compare muscular coactivation during walking between older adults with fear of falling and older adults without fear of falling. Thirty-eight healthy older adults (82.3 ± 6.8 years) participated in this study. Walking speed and step length were measured. Electromyography (EMG) data were collected from the tibialis anterior and soleus during walking to calculate the co-contraction index (CI). Subjects were divided into those with fear of falling and those without fear of falling, on the basis of a modified Falls Efficacy Scale ([[FES]]). Stepwise multiple regression analysis was used, with CI as the dependent variable, and fear of falling, experience of falling (during the past year), walking speed, step length, and age as independent variables. Mean values of CI during walking, walking speed, and step length were 51.9 ± 11.7%, 0.90 ± 0.40 m/s, and 0.43±0.11 m, respectively. Eight subjects (21.1%) had fallen within the past year, and 19 subjects (50.0%) had fear of falling. All subjects without fear of falling had [[FES]] scores of 10 (maximum score). Subjects with fear of falling had a median [[FES]] score of 17 (interquartile range, 13 to 25). Stepwise multiple regression analysis revealed that fear of falling remained significantly associated with CI (p<0.01): CIs for subjects with fear and those without fear were 59.5 ± 12.2% and 46.7 ± 8.5%, respectively. Individuals with a fear of falling have increased muscular co-activation at the ankle joint during walking, at least in a certain subgroup of older adults. Further research is needed to clarify negative and positive effects of muscular coactivation during walking in fearful subjects.
|mesh-terms=* Accidental Falls
* Age Factors
* Aged, 80 and over
* Aging
* Electromyography
* Fear
* Female
* Humans
* Male
* Muscle, Skeletal
* Postural Balance
* Posture
* Walking

|full-text-url=https://sci-hub.do/10.3275/7716
}}
{{medline-entry
|title=Vulnerability in high-functioning persons aged 65 to 70 years: the importance of the fear factor.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19966536
|abstract=Falls efficacy has been shown to predict functional decline, but whether it is independently associated with frailty is still unclear. This study investigated the cross-sectional association between falls efficacy and the frailty phenotype in high-functioning older persons. Subjects (n=861) were a sub-sample of community-dwelling persons aged 65 to 70 years enrolled in the "Lc65 " cohort, who had gait assessment. Data included demographics, functional, cognitive, affective and health status, as well as measures of physical performance. Falls efficacy was measured with the Falls Efficacy Scale-International ([[FES]]-I) and frailty with Fried's criteria. Participants were categorized into robust (no frailty criterion) and vulnerable (1 or more criteria). Low falls efficacy was defined as a [[FES]]-I score in the lowest quartile. Overall, 23.9% of participants were vulnerable. Compared with robust participants, they were more likely to report low falls efficacy (43.3% vs 19.1%, p<0.001) and had poorer health and functional and mental status. They had slower gait speed (1.07 /-0.18 vs 1.15 /-0.15 m/s, p<0.001) and increased gait speed variability (coefficient of variation 4.10 /-4.03 vs 3.33 /-1.45%, p<0.001), although only 6 participants (0.7%) fulfilled Fried's slow walking criterion. In multivariate analysis, low falls efficacy remained associated with being vulnerable (adjusted OR 1.80, 95% CI 1.19-2.74, p=0.006), independent of comorbidity, functional status, falls history and gait performance. In high-functioning older persons, low falls efficacy was associated with vulnerability, even after controlling for gait performance and falls history. Whether low falls efficacy is a potential target on the pathway leading to frailty should be further examined prospectively.
|mesh-terms=* Accidental Falls
* Activities of Daily Living
* Aged
* Aging
* Cross-Sectional Studies
* Disability Evaluation
* Exercise
* Fear
* Female
* Frail Elderly
* Gait
* Humans
* Male
* Physical Fitness
* Self Efficacy
* Surveys and Questionnaires

|full-text-url=https://sci-hub.do/10.1007/BF03324799
}}
{{medline-entry
|title=Validation of the Falls Efficacy Scale and Falls Efficacy Scale International in geriatric patients with and without cognitive impairment: results of self-report and interview-based questionnaires.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19729878
|abstract=Frail, old patients with and without cognitive impairment are at high risk of falls and associated medical and psychosocial issues. The lack of adequate, validated instruments has partly hindered research in this field. So far no questionnaire documenting fall-related self-efficacy/fear of falling has been validated for older persons with cognitive impairment or for different administration methods such as self-report or interview. To validate the self-report and interview version of the Falls Efficacy Scale ([[FES]]) and the Falls Efficacy Scale International Version ([[FES]]-I) in frail geriatric patients with and without cognitive impairment. 156 geriatric patients in geriatric rehabilitations wards with (n = 75) and without cognitive impairment (n = 81) were included in this study. Reports of fall-related self-efficacy were based on self-reported and interview-based questionnaires. Descriptive statistics, reliability estimates and validation results were computed for the total group and sub-samples with respect to cognitive status, for the 2 different questionnaires ([[FES]]/[[FES]]-I) and for the 2 administration methods. Test-retest reliability was tested in a subsample of 62 patients. Internal reliability and test-retest reliability were good to excellent in both the [[FES]] and [[FES]]-I, with the [[FES]]-I showing better internal reliability and the [[FES]] better test-retest reliability with respect to cognitively impaired persons. The group of cognitively impaired persons tended to show lower test-retest reliability and mean fall-related self-efficacy and had significantly lower completion rates in self-administered questionnaires. As indicated by significant differences in parameters closely related to falls, such as vertigo, functional performances, fear of falling and history of falls, both the [[FES]] and the [[FES]]-I showed good construct validity. Effect sizes computed for the above-mentioned groups for fall-related parameters confirmed the results of construct validation. Both the [[FES]] as well as the [[FES]]-I showed good to excellent measurement properties in persons with and without moderate cognitive impairment. In frail older persons, especially in persons with cognitive impairment, an interview-based administration method is recommended.
|mesh-terms=* Accidental Falls
* Aged
* Aged, 80 and over
* Aging
* Dementia
* Fear
* Female
* Frail Elderly
* Humans
* Male
* Middle Aged
* Surveys and Questionnaires

|full-text-url=https://sci-hub.do/10.1159/000236027
}}
{{medline-entry
|title=Convergent and predictive validity of three scales related to falls in the elderly.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/14763641
|abstract=The purpose of this study was to determine if the Activities-specific Balance Confidence (ABC) Scale, Falls Efficacy Scale ([[FES]]), and Survey of Activities and Fear of Falling in the Elderly (SAFE) assessments measured fear of falling in the same manner (convergent validity) and to determine if they predicted those individuals who, based upon a previous history of falls, limitation of activity, and not leaving home, had an increased potential for falling (predictive validity). One hundred and eighteen individuals, 60 years of age and older, completed each of the assessments. They self-reported activity restriction, fall history, and the number of times they left the home each week. The convergent validity of each assessment was established by correlating each assessment tool with each of the others. Findings indicated the ABC and [[FES]] were highly correlated with each other, indicating they measured similar constructs, and both were moderately correlated with the SAFE, suggesting these assessments measured different constructs. The predictive validity of each instrument in relation to the frequency of falls, limitation of activity, and frequency of leaving the home revealed no individual tool could accurately predict any of these characteristics of the sample. As a result, no one test by itself was able to identify individuals who may be at risk and a candidate for an intervention program.
|mesh-terms=* Accidental Falls
* Aged
* Aged, 80 and over
* Fear
* Geriatrics
* Humans
* Middle Aged
* Reproducibility of Results
* Surveys and Questionnaires

|full-text-url=https://sci-hub.do/10.5014/ajot.58.1.100
}}
{{medline-entry
|title=Prospective study of the impact of fear of falling on activities of daily living, SF-36 scores, and nursing home admission.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10819321
|abstract=The aim of this study was to assess the impact of fear of falling on the health of older people. A total of 528 subjects (mean age 77 years) were recruited from two hospitals in Sydney, Australia, and followed for approximately 12 months. Eighty-five subjects died during follow-up, and 31 were admitted to an aged care institution. Tinetti's Falls Efficacy Scale ([[FES]]) was successfully administered to 418 subjects as part of the baseline assessment. Among those with baseline [[FES]] scores, ability to perform 10 activities of daily living (ADLs) was assessed at baseline and follow-up in 307 subjects, and SF-36 scores were assessed at baseline and follow-up in 90 subjects recruited during the latter part of the study. Falls during follow-up were identified using a monthly falls calendar. Compared with those with a high fall-related self-efficacy ([[FES]] score = 100), those with a low fall-related self-efficacy ([[FES]] score < or = 75) had an increased risk of falling (adjusted relative risk 2.09, 95% confidence interval [CI] 1.31-3.33). Those with poorer fall-related self-efficacy had greater declines in ability to perform ADLs (p < .001): the total ADL score decreased by 0.69 activities among persons with low [[FES]] scores (< or =75) but decreased by only 0.04 activities among persons with [[FES]] scores of 100. Decline in ADLs was not explained by the higher frequency of falls among persons with low [[FES]] scores. SF-36 scores (particularly scores on the Physical Function and Bodily Pain subscales) tended to decline more among persons with poor fall-related self-efficacy. Nonfallers who said they were afraid of falling had an increased risk of admission to an aged care institution. Fear of falling has serious consequences for older people. Interventions that successfully reduce fear of falling and improve fall-related self-efficacy are likely to have major health benefits.
|mesh-terms=* Accidental Falls
* Activities of Daily Living
* Aged
* Aging
* Australia
* Disability Evaluation
* Fear
* Female
* Homes for the Aged
* Humans
* Linear Models
* Male
* Nursing Homes
* Patient Admission
* Proportional Hazards Models
* Prospective Studies
* Self Efficacy
* Surveys and Questionnaires

|full-text-url=https://sci-hub.do/10.1093/gerona/55.5.m299
}}

FER1L6

2021-05-12T15:36:20Z

OdysseusBot: Новая страница: «protein 6 [C8orfK23] ==Publications== {{medline-entry |title=Genome-wide association study and annotating candidate gene networks affecting age at first calving...»

protein 6 [C8orfK23]

==Publications==

{{medline-entry
|title=Genome-wide association study and annotating candidate gene networks affecting age at first calving in Nellore cattle.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28994157
|abstract=We performed a genome-wide mapping for the age at first calving (AFC) with the goal of annotating candidate genes that regulate fertility in Nellore cattle. Phenotypic data from 762 cows and 777k SNP genotypes from 2,992 bulls and cows were used. Single nucleotide polymorphism (SNP) effects based on the single-step GBLUP methodology were blocked into adjacent windows of 1 Megabase (Mb) to explain the genetic variance. SNP windows explaining more than 0.40% of the AFC genetic variance were identified on chromosomes 2, 8, 9, 14, 16 and 17. From these windows, we identified 123 coding protein genes that were used to build gene networks. From the association study and derived gene networks, putative candidate genes (e.g., [[PAPPA]], [[PREP]], [[FER1L6]], [[TPR]], [[NMNAT1]], [[ACAD10]], [[PCMTD1]], [[CRH]], OPKR1, [[NPBWR1]] and NCOA2) and transcription factors (TF) (STAT1, [[STAT3]], [[RELA]], [[E2F1]] and EGR1) were strongly associated with female fertility (e.g., negative regulation of luteinizing hormone secretion, folliculogenesis and establishment of uterine receptivity). Evidence suggests that AFC inheritance is complex and controlled by multiple loci across the genome. As several windows explaining higher proportion of the genetic variance were identified on chromosome 14, further studies investigating the interaction across haplotypes to better understand the molecular architecture behind AFC in Nellore cattle should be undertaken.
|mesh-terms=* Aging
* Animals
* Breeding
* Cattle
* Female
* Fertility
* Gene Regulatory Networks
* Genome-Wide Association Study
* Genotype
* Phenotype
* Polymorphism, Single Nucleotide
* Quantitative Trait Loci
|keywords=* beef cattle
* gene function
* single-step
|full-text-url=https://sci-hub.do/10.1111/jbg.12299
}}

FDXR

2021-05-12T15:36:16Z

OdysseusBot: Новая страница: «NADPH:adrenodoxin oxidoreductase, mitochondrial precursor (EC 1.18.1.6) (AR) (Adrenodoxin reductase) (Ferredoxin--NADP( ) reductase) (Ferredoxin reductase) [ADXR]...»

NADPH:adrenodoxin oxidoreductase, mitochondrial precursor (EC 1.18.1.6) (AR) (Adrenodoxin reductase) (Ferredoxin--NADP( ) reductase) (Ferredoxin reductase) [ADXR]

==Publications==

{{medline-entry
|title=The aged testis. A good model to find proteins involved in age-related changes of testis by proteomic analysis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24597284
|abstract=To explore associated proteins involved in age-related changes of the testis and better understand the roles of these proteins in the human testis. We used two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spec trometry analysis to identify differentially expressed proteins between the aged and the normal control groups. The L-lactate dehydrogenase C chain ([[LDHC]]) protein, a previous testis-specific protein, was found to be downregulated in the aged testis and was further tested with western blot and immunohistochemical analysis to verify the result of the [[LDHC]] protein in 2-DE. Twelve differentially expressed proteins were identified. Among those proteins, 3 were upregulated and 9 were downregulated in the aged group. The results of western blot and immunohistochemical analysis confirmed the expression of [[LDHC]] downregulation in the aged testis. Some proteins identified had little well-known function in the human testis, as follows: [[AKR7A3]], [[FDXR]], [[PGAM1]], SEPT2 and [[HMGCS2]]. Our results imply that the aged testis can be a good model to find associated proteins involved in age-related changes of the testis. It can be useful to understand the roles of those proteins in the testis.
|mesh-terms=* Aged
* Aging
* Down-Regulation
* Electrophoresis, Gel, Two-Dimensional
* Humans
* Immunohistochemistry
* Isoenzymes
* L-Lactate Dehydrogenase
* Male
* Middle Aged
* Proteins
* Proteomics
* Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
* Testis
* Young Adult

}}

FDPS

2021-05-12T15:36:13Z

OdysseusBot: Новая страница: «Farnesyl pyrophosphate synthase (EC 2.5.1.10) (FPP synthase) (FPS) ((2E,6E)-farnesyl diphosphate synthase) (Dimethylallyltranstransferase) (EC 2.5.1.1) (Farnesyl...»

Farnesyl pyrophosphate synthase (EC 2.5.1.10) (FPP synthase) (FPS) ((2E,6E)-farnesyl diphosphate synthase) (Dimethylallyltranstransferase) (EC 2.5.1.1) (Farnesyl diphosphate synthase) (Geranyltranstransferase) [FPS] [KIAA1293]

==Publications==

{{medline-entry
|title=Targeting the phospholipase A2 receptor ameliorates premature aging phenotypes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30216637
|abstract=Hutchinson-Gilford progeria syndrome (HGPS) is a lethal premature aging that recapitulates many normal aging characteristics. This disorder is caused by mutation in the [[LMNA]] gene leading to the production of progerin which induces misshapen nuclei, cellular senescence, and aging. We previously showed that the phospholipase A2 receptor ([[PLA2R1]]) promotes senescence induced by replicative, oxidative, and oncogenic stress but its role during progerin-induced senescence and in progeria is currently unknown. Here, we show that knockdown of [[PLA2R1]] prevented senescence induced by progerin expression in human fibroblasts and markedly delayed senescence of HGPS patient-derived fibroblasts. Whole-body knockout of Pla2r1 in a mouse model of progeria decreased some premature aging phenotypes, such as rib fracture and decreased bone content, together with decreased senescence marker. Progerin-expressing human fibroblasts exhibited a high frequency of misshapen nuclei and increased farnesyl diphosphate synthase ([[FDPS]]) expression compared to controls; knockdown of [[PLA2R1]] reduced the frequency of misshapen nuclei and normalized [[FDPS]] expression. Pamidronate, a [[FDPS]] inhibitor, also reduced senescence and misshapen nuclei. Downstream of [[PLA2R1]], we found that p53 mediated the progerin-induced increase in [[FDPS]] expression and in misshapen nuclei. These results suggest that [[PLA2R1]] mediates key premature aging phenotypes through a p53/[[FDPS]] pathway and might be a new therapeutic target.
|mesh-terms=* Aging, Premature
* Animals
* Cell Line
* Cell Nucleus
* Cell Nucleus Shape
* Cellular Senescence
* Disease Models, Animal
* Geranyltranstransferase
* Humans
* Lamin Type A
* Mice, Inbred C57BL
* Phenotype
* Progeria
* Receptors, Phospholipase A2
* Tumor Suppressor Protein p53
|keywords=* cellular senescence
* p53
* progeroid diseases
* signaling
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260922
}}
{{medline-entry
|title=Alteration of enzyme expressions in mevalonate pathway: possible role for cardiovascular remodeling in spontaneously hypertensive rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21467659
|abstract=The mevalonate pathway is an important metabolic pathway that plays a key role in multiple cellular processes. The aim of this study was to define whether the enzyme expression in mevalonate pathway changes during cardiovascular remodelling in spontaneously hypertensive rats (SHR). Hearts and thoracic aortas were removed for the study of cardiovascular remodeling in SHR and Wistar-Kyoto rats (WKY). The protein expression of the enzymes in hearts, aortas and livers was analyzed by western blot. The histological measurements showed that the mass and the size of cardiomyocytes, the media thickness and the media cross-sectional area (MCSA) of the thoracic aorta were all increased in SHR since 3 weeks of age. In the heart, there was overexpression of some enzymes, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), farnesyl diphosphate synthase ([[FDPS]]), and geranylgeranyltransferase type I (GGTase-I), and downregulation of squalene synthetase (SQS) in SHR since 3 weeks of age. In the aorta, besides similar expressions of HMGR, SQS, [[FDPS]] and GGTase-I as in the heart, there was upregulation of farnesyltransferase α at 16 and 25 weeks of age and of farnesyltransferase β in 25-weeks-old SHR. Western blot demonstrated overexpression of HMGR and downregulation of SQS in SHR livers at all ages tested. The cardiovascular remodeling of SHR preceded the development of hypertension, and altered expression of several key enzymes in the mevalonate pathway may play a potential pathophysiological role in cardiovascular remodeling.
|mesh-terms=* Age Factors
* Aging
* Alkyl and Aryl Transferases
* Analysis of Variance
* Animals
* Aorta, Thoracic
* Blood Pressure
* Blotting, Western
* Cholesterol, HDL
* Cholesterol, LDL
* Disease Models, Animal
* Farnesyl-Diphosphate Farnesyltransferase
* Farnesyltranstransferase
* Geranyltranstransferase
* Hydroxymethylglutaryl CoA Reductases
* Hypertension
* Liver
* Male
* Mevalonic Acid
* Myocardium
* Rats
* Rats, Inbred SHR
* Rats, Inbred WKY
* Ventricular Remodeling

|full-text-url=https://sci-hub.do/10.1253/circj.cj-10-1101
}}

FCGR3A

2021-05-12T15:36:11Z

OdysseusBot: Новая страница: «Low affinity immunoglobulin gamma Fc region receptor III-A precursor (CD16a antigen) (Fc-gamma RIII-alpha) (Fc-gamma RIII) (Fc-gamma RIIIa) (FcRIII) (FcRIIIa) (Fc...»

Low affinity immunoglobulin gamma Fc region receptor III-A precursor (CD16a antigen) (Fc-gamma RIII-alpha) (Fc-gamma RIII) (Fc-gamma RIIIa) (FcRIII) (FcRIIIa) (FcR-10) (IgG Fc receptor III-2) (CD16a antigen) [CD16A] [FCG3] [FCGR3] [IGFR3]

==Publications==

{{medline-entry
|title=Genomic regulation of senescence and innate immunity signaling in the retinal pigment epithelium.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25963977
|abstract=The tumor suppressor p53 is a major regulator of genes important for cell cycle arrest, senescence, apoptosis, and innate immunity, and has recently been implicated in retinal aging. In this study we sought to identify the genetic networks that regulate p53 function in the retina using quantitative trait locus (QTL) analysis. First we examined age-associated changes in the activation and expression levels of p53; known p53 target proteins and markers of innate immune system activation in primary retinal pigment epithelial ([[RPE]]) cells that were harvested from young and aged human donors. We observed increased expression of p53, activated caspase-1, [[CDKN1A]], [[[[CDKN2A]]]] (p16INK4a), [[TLR4]], and IFNα in aged primary [[RPE]] cell lines. We used the Hamilton Eye Institute (HEI) retinal dataset ( www.genenetwork.org ) to identify genomic loci that modulate expression of genes in the p53 pathway in recombinant inbred BXD mouse strains using a QTL systems biology-based approach. We identified a significant trans-QTL on chromosome 1 (region 172-177 Mb) that regulates the expression of Cdkn1a. Many of the genes in this QTL locus are involved in innate immune responses, including Fc receptors, interferon-inducible family genes, and formin 2. Importantly, we found an age-related increase in [[FCGR3A]] and [[FMN2]] and a decrease in [[IFI16]] levels in [[RPE]] cultures. There is a complex multigenic innate immunity locus that controls expression of genes in the p53 pathway in the [[RPE]], which may play an important role in modulating age-related changes in the retina.
|mesh-terms=* Adult
* Aged, 80 and over
* Aging
* Animals
* Apoptosis
* Caspases
* Caspases, Initiator
* Cell Line
* Cyclin-Dependent Kinase Inhibitor p16
* Cyclin-Dependent Kinase Inhibitor p21
* Gene Expression Regulation
* Humans
* Immunity, Innate
* Interferon-alpha
* Interferon-gamma
* Mice
* Mice, Inbred BALB C
* Mice, Inbred C57BL
* Mice, Inbred DBA
* Primary Cell Culture
* Quantitative Trait Loci
* Retinal Pigment Epithelium
* Signal Transduction
* Toll-Like Receptor 4
* Tumor Suppressor Protein p53

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450138
}}

FCGR2A

2021-05-12T15:36:08Z

OdysseusBot: Новая страница: «Low affinity immunoglobulin gamma Fc region receptor II-a precursor (IgG Fc receptor II-a) (CDw32) (Fc-gamma RII-a) (Fc-gamma-RIIa) (FcRII-a) (CD32 antigen) [CD32...»

Low affinity immunoglobulin gamma Fc region receptor II-a precursor (IgG Fc receptor II-a) (CDw32) (Fc-gamma RII-a) (Fc-gamma-RIIa) (FcRII-a) (CD32 antigen) [CD32] [FCG2] [FCGR2A1] [IGFR2]

==Publications==

{{medline-entry
|title=Impact of C-reactive protein on osteo-/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31377747
|abstract=Medial vascular calcification occurs during the aging process and is strongly accelerated by chronic kidney disease (CKD). Elevated C-reactive protein ([[CRP]]) levels are associated with vascular calcification, cardiovascular events and mortality in CKD patients. [[CRP]] is an important promoter of vascular inflammation. Inflammatory processes are critically involved in initiation and progression of vascular calcification. Thus, the present study explored a possible impact of [[CRP]] on vascular calcification. We found that [[CRP]] promoted osteo-/chondrogenic transdifferentiation and aggravated phosphate-induced osteo-/chondrogenic transdifferentiation and calcification of primary human aortic smooth muscle cells (HAoSMCs). These effects were paralleled by increased cellular oxidative stress and corresponding pro-calcific downstream-signaling. Antioxidants or p38 MAPK inhibition suppressed [[CRP]]-induced osteo-/chondrogenic signaling and mineralization. Furthermore, silencing of Fc fragment of IgG receptor IIa ([[FCGR2A]]) blunted the pro-calcific effects of [[CRP]]. Vascular [[CRP]] expression was increased in the klotho-hypomorphic mouse model of aging as well as in HAoSMCs during calcifying conditions. In conclusion, [[CRP]] augments osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells through mechanisms involving [[FCGR2A]]-dependent induction of oxidative stress. Thus, systemic inflammation may actively contribute to the progression of vascular calcification.
|mesh-terms=* Aging
* Animals
* C-Reactive Protein
* Cell Transdifferentiation
* Cells, Cultured
* Chondrogenesis
* Disease Models, Animal
* Glucuronidase
* Humans
* Mice
* Muscle, Smooth, Vascular
* Myocytes, Smooth Muscle
* Osteogenesis
* Oxidative Stress
* RNA, Small Interfering
* Receptors, IgG
* Renal Insufficiency, Chronic
* Signal Transduction
* Vascular Calcification
|keywords=* CKD
* CRP
* osteo-/chondrogenic signaling
* oxidative stress
* vascular calcification
* vascular smooth muscle cells
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710049
}}
{{medline-entry
|title=The [[FCGR2A]]--Arg131 variant is no major mortality factor in the elderly--evidence from a German centenarian study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16893392
|abstract=The functional single nucleotide polymorphism rs1801274 in the [[FCGR2A]] gene (His131Arg) influences the efficiency of hIgG2 binding, the main isotype produced in response to encapsulated bacteria like Streptococcus pneumoniae and Haemophilus influenzae. In contrast to the receptor with the His131 allele, FcgammaRIIa-Arg131 binds hIgG2 poorly and carriers of this variant have been shown to be much more susceptible to succumb to bacterial pneumonia or meningitis. As bacteraemic pneumonia is one of the leading causes of death in elderly individuals, we hypothesized that the Arg131 variant could be a major mortality factor in the old. We analysed the [[FCGR2A]]-His131Arg polymorphism in a group of 408 German centenarians and two samples of younger Germans aged 60-75 and 18-49 years, respectively. No statistically significant differences were observed between the three age groups, neither at the allele nor at the genotype level. Apparently, the ability to reach old age is largely unaffected by the genetically determined efficacy of the [[FCGR2A]]-based immune response. However, the severely reduced ability of [[FCGR2A]]-131Arg carriers to eliminate encapsulated bacteria must apparently be compensated by an alternative mechanism, possibly involving other genetic survival factors.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Amino Acid Substitution
* Genetic Predisposition to Disease
* Germany
* Haemophilus Infections
* Haemophilus influenzae
* Humans
* Longevity
* Middle Aged
* Pneumonia, Bacterial
* Pneumonia, Pneumococcal
* Polymorphism, Single Nucleotide
* Receptors, IgG
* Streptococcus pneumoniae

|full-text-url=https://sci-hub.do/10.1111/j.1744-313X.2006.00613.x
}}

FCER1G

2021-05-12T15:36:05Z

OdysseusBot: Новая страница: «High affinity immunoglobulin epsilon receptor subunit gamma precursor (Fc receptor gamma-chain) (FcRgamma) (Fc-epsilon RI-gamma) (IgE Fc receptor subunit gamma) (...»

High affinity immunoglobulin epsilon receptor subunit gamma precursor (Fc receptor gamma-chain) (FcRgamma) (Fc-epsilon RI-gamma) (IgE Fc receptor subunit gamma) (FceRI gamma)

==Publications==

{{medline-entry
|title=A Microglial Signature Directing Human Aging and Neurodegeneration-Related Gene Networks.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30733664
|abstract=Aging is regarded as a major risk factor for neurodegenerative diseases. Thus, a better understanding of the similarities between the aging process and neurodegenerative diseases at the cellular and molecular level may reveal better understanding of this detrimental relationship. In the present study, we mined publicly available gene expression datasets from healthy individuals and patients affected by neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and Huntington's disease) across a broad age spectrum and compared those with mouse aging and mouse cell-type specific gene expression profiles. We performed weighted gene co-expression network analysis (WGCNA) and found a gene network strongly related with both aging and neurodegenerative diseases. This network was significantly enriched with a microglial signature as imputed from cell type-specific sequencing data. Since mouse models are extensively used for the study of human diseases, we further compared these human gene regulatory networks with age-specific mouse brain transcriptomes. We discovered significantly preserved networks with both human aging and human disease and identified 17 shared genes in the top-ranked immune/microglia module, among which we found five human hub genes [i]TYROBP, [[FCER1G]], [[ITGB2]], [[MYO1F]], PTPRC[/i], and two mouse hub genes [i]Trem2[/i] and [i]C1qa[/i]. Taken together, these results support the hypothesis that microglia are key players involved in human aging and neurodegenerative diseases, and suggest that mouse models should be appropriate for studying these microglial changes in human.

|keywords=* Alzheimer
* Parkinson
* WGCNA
* aging
* bioinformatics
* gene networks
* microglia
* neurodegeneration
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353788
}}

FBXO7

2021-05-12T15:36:01Z

OdysseusBot: Новая страница: «F-box only protein 7 [FBX7] ==Publications== {{medline-entry |title=The FBXO7 homologue nutcracker and binding partner PI31 in Drosophila melanogaster model...»

F-box only protein 7 [FBX7]

==Publications==

{{medline-entry
|title=The [[FBXO7]] homologue nutcracker and binding partner PI31 in Drosophila melanogaster models of Parkinson's disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27936908
|abstract=Parkinsonian-pyramidal syndrome (PPS) is an early onset form of Parkinson's disease (PD) that shows degeneration of the extrapyramidal region of the brain to result in a severe form of PD. The toxic protein build-up has been implicated in the onset of PPS. Protein removal is mediated by an intracellular proteasome complex: an E3 ubiquitin ligase, the targeting component, is essential for function. [[FBXO7]] encodes the F-box component of the SCF E3 ubiquitin ligase linked to familial forms of PPS. The Drosophila melanogaster homologue nutcracker (ntc) and a binding partner, PI31, have been shown to be active in proteasome function. We show that altered expression of either ntc or PI31 in dopaminergic neurons leads to a decrease in longevity and locomotor ability, phenotypes both associated with models of PD. Furthermore, expression of ntc-RNAi in an established α-synuclein-dependent model of PD rescues the phenotypes of diminished longevity and locomotor control.
|mesh-terms=* Animals
* Animals, Genetically Modified
* Carrier Proteins
* Disease Models, Animal
* Drosophila Proteins
* Drosophila melanogaster
* Eye
* F-Box Proteins
* Female
* Gene Expression
* Longevity
* Male
* Organ Specificity
* Organogenesis
* Parkinson Disease
* Protein Binding
* Protein Interaction Domains and Motifs
* alpha-Synuclein
|keywords=* Drosophila melanogaster
* FBXO7
* PI31
* Parkinson Disease
* maladie de Parkinson
* neurodegeneration
* neurodégénérescence
* nutcracker
|full-text-url=https://sci-hub.do/10.1139/gen-2016-0087
}}

FBXO33

2021-05-12T15:35:55Z

OdysseusBot: Новая страница: «F-box only protein 33 [FBX33] ==Publications== {{medline-entry |title=Quantitative and Qualitative Role of Antagonistic Heterogeneity in Genetics of Blood Lipid...»

F-box only protein 33 [FBX33]

==Publications==

{{medline-entry
|title=Quantitative and Qualitative Role of Antagonistic Heterogeneity in Genetics of Blood Lipids.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31566214
|abstract=Prevailing strategies in genome-wide association studies (GWAS) mostly rely on principles of medical genetics emphasizing one gene, one function, one phenotype concept. Here, we performed GWAS of blood lipids leveraging a new systemic concept emphasizing complexity of genetic predisposition to such phenotypes. We focused on total cholesterol, low- and high-density lipoprotein cholesterols, and triglycerides available for 29,902 individuals of European ancestry from seven independent studies, men and women combined. To implement the new concept, we leveraged the inherent heterogeneity in genetic predisposition to such complex phenotypes and emphasized a new counter intuitive phenomenon of antagonistic genetic heterogeneity, which is characterized by misalignment of the directions of genetic effects and the phenotype correlation. This analysis identified 37 loci associated with blood lipids but only one locus, [[FBXO33]], was not reported in previous top GWAS. We, however, found strong effect of antagonistic heterogeneity that leaded to profound (quantitative and qualitative) changes in the associations with blood lipids in most, 25 of 37 or 68%, loci. These changes suggested new roles for some genes, which functions were considered as well established such as [[GCKR]], [[SIK3]] (APOA1 locus), [[LIPC]], [[LIPG]], among the others. The antagonistic heterogeneity highlighted a new class of genetic associations emphasizing beneficial and adverse trade-offs in predisposition to lipids. Our results argue that rigorous analyses dissecting heterogeneity in genetic predisposition to complex traits such as lipids beyond those implemented in current GWAS are required to facilitate translation of genetic discoveries into health care.

|keywords=* Age-related phenotypes
* Aging
* Genome-wide association studies
* Health span
* Life span
* Pleiotropy
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518561
}}