Публикации о генах и старении (titles): различия между версиями

==BRAF==

|title=Conditional reprograming culture conditions facilitate growth of lower grade glioma models.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33258947

|abstract=The conditional reprogramming cell culture method was developed to facilitate growth of senescence-prone normal and neoplastic epithelial cells, and involves co-culture with irradiated fibroblasts and the addition of a small molecule Rho kinase (ROCK) inhibitor. The aim of this study was to determine whether this approach would facilitate the culture of compact low grade gliomas. We attempted to culture 4 pilocytic astrocytomas, 2 gangliogliomas, 2 myxopapillary ependymomas, 2 anaplastic gliomas, 2 difficult-to-classify low grade neuroepithelial tumors, a desmoplastic infantile ganglioglioma, and an anaplastic pleomorphic xanthoastrocytoma using a modified conditional reprogramming cell culture approach. Conditional reprogramming resulted in robust increases in growth for a majority of these tumors, with fibroblast conditioned media and ROCK inhibition both required. Switching cultures to standard serum containing media, or serum free neurosphere conditions, with or without ROCK inhibition, resulted in decreased proliferation and induction of senescence markers. ROCK inhibition and conditioned media both promoted Akt and Erk1/2 activation. Several cultures, including one derived from a NF1-associated pilocytic astrocytoma (JHH-NF1-PA1) and one from a [[BRAF]] p.V600E mutant anaplastic pleomorphic xanthoastrocytoma (JHH-PXA1), exhibited growth sufficient for preclinical testing in vitro. In addition, JHH-NF1-PA1 cells survived and migrated in larval zebrafish orthotopic xenografts, while JHH-PXA1 formed orthotopic xenografts in mice histopathologically similar to the tumor from which it was derived. These studies highlight the potential for the conditional reprogramming cell culture method to promote the growth of glial and glioneuronal tumors in vitro, in some cases enabling the establishment of long-term culture and in vivo models.

|keywords=* BRAFV600E

* Conditional reprogramming

* NF1

* Senescence

* low grade glioma

|full-text-url=https://sci-hub.do/10.1093/neuonc/noaa263

==MSC==

|title=Extracellular vesicles derived from bone marrow mesenchymal stem cells enhance myelin maintenance after cortical injury in aged rhesus monkeys.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33264634

|abstract=Cortical injury, such as stroke, causes neurotoxic cascades that lead to rapid death and/or damage to neurons and glia. Axonal and myelin damage in particular, are critical factors that lead to neuronal dysfunction and impair recovery of function after injury and can be exacerbated in the aged brain where white matter damage is prevalent. Therapies that can ameliorate myelin damage and promote repair by targeting oligodendroglia, the cells that produce and maintain myelin, may facilitate recovery after injury, especially in the aged brain where these processes are already compromised. We previously reported that a novel therapeutic, Mesenchymal Stem Cell derived extracellular vesicles ([[MSC]]-EVs), administered intravenously at both 24 h and 14 days after cortical injury reduced microgliosis (Go et al. 2019), reduced neuronal pathology (Medalla et al. 2020), and improved motor recovery (Moore et al. 2019) in aged female rhesus monkeys. Here, we evaluated the effect of treatment with [[MSC]]-EVs on changes in oligodendrocyte maturation and associated myelin markers in the sublesional white matter using immunohistochemistry, confocal microscopy, stereology, qRT-PCR, and ELISA. Compared to vehicle-treated control, EV-treated monkeys showed a reduction in the density of damaged oligodendrocytes. Further, EV-treatment was associated with enhanced myelin maintenance, evidenced by upregulation of myelin-related genes and increases in actively-myelinating oligodendrocytes in in sublesional white matter. These changes in myelination correlate with the rate of motor recovery, suggesting that improved myelin maintenance facilitates this recovery. Overall, our results suggest that EVs act on oligodendrocytes to support myelination and likely improve functional recovery after injury in the aged brain. SIGNIFICANCE: We previously reported that after cortical injury in the aged monkey brain, EVs reduce neuronal pathology (Medalla et al. 2020), microgliosis (Go et al. 2019), and facilitate recovery of function. However, the effect of injury on oligodendrocytes and myelination has not been characterized in the primate brain (Dewar et al. 1999; Sozmen et al. 2012; Zhang et al. 2013). In the present study, we assessed changes in myelination after cortical injury in these same aged monkeys. Our results show, for the first time, that [[MSC]]-EVs support recovery of function after cortical injury by enhancing myelin maintenance in the aged primate brain.

|title=Rejuvenation of Senescent Endothelial Progenitor Cells by Extracellular Vesicles Derived From Mesenchymal Stromal Cells.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33294742

|abstract=Mesenchymal stromal cell ([[MSC]]) transplantation is a form of the stem-cell therapy that has shown beneficial effects for many diseases. The use of stem-cell therapy, including [[MSC]] transplantation, however, has limitations such as the tumorigenic potential of stem cells and the lack of efficacy of aged autologous cells. An ideal therapeutic approach would keep the beneficial effects of [[MSC]] transplantation while circumventing the limitations associated with the use of intact stem cells. This study provides proof-of-concept evidence that [[MSC]]-derived extracellular vesicles represent a promising platform to develop an acellular therapeutic approach that would just do that. Extracellular vesicles are membranous vesicles secreted by [[MSC]]s and contain bioactive molecules to mediate communication between different cells. Extracellular vesicles can be taken up by recipient cells, and once inside the recipient cells, the bioactive molecules are released to exert the beneficial effects on the recipient cells. This study, for the first time to our knowledge, shows that extracellular vesicles secreted by [[MSC]]s recapitulate the beneficial effects of [[MSC]]s on vascular repair and promote blood vessel regeneration after ischemic events. Furthermore, [[MSC]]s from aged donors can be engineered to produce extracellular vesicles with improved regenerative potential, comparable to [[MSC]]s from young donors, thus eliminating the need for allogenic young donors for elderly patients.

|keywords=* BM, bone marrow

* PBS, phosphate-buffered saline

* angiogenesis

* extracellular vesicles

* lin− BMC, lineage negative bone marrow cell

* miR, microRNA

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691285

==HES1==

|title=A Single-Cell Transcriptomic Atlas of Human Skin Aging.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33238152

|abstract=Skin undergoes constant self-renewal, and its functional decline is a visible consequence of aging. Understanding human skin aging requires in-depth knowledge of the molecular and functional properties of various skin cell types. We performed single-cell RNA sequencing of human eyelid skin from healthy individuals across different ages and identified eleven canonical cell types, as well as six subpopulations of basal cells. Further analysis revealed progressive accumulation of photoaging-related changes and increased chronic inflammation with age. Transcriptional factors involved in the developmental process underwent early-onset decline during aging. Furthermore, inhibition of key transcription factors [[HES1]] in fibroblasts and KLF6 in keratinocytes not only compromised cell proliferation, but also increased inflammation and cellular senescence during aging. Lastly, we found that genetic activation of [[HES1]] or pharmacological treatment with quercetin alleviated cellular senescence of dermal fibroblasts. These findings provide a single-cell molecular framework of human skin aging, providing a rich resource for developing therapeutic strategies against aging-related skin disorders.

|keywords=* HES1

* KLF6

* fibroblast

* keratinocyte

|full-text-url=https://sci-hub.do/10.1016/j.devcel.2020.11.002

==HR==

|title=Patients with hip fracture and total hip arthroplasty surgery differ in anthropometric, but not cardiovascular screening abnormalities.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33267795

|abstract=With the rising number of hip surgeries, simple and cost-effective tools for surgery risk assessment are warranted. The analysis of heart rate variability ([[HR]]V) may not only provide critical insights into the general frailty of patients with hip surgery, but also allow for better differentiation of health profiles in different hip surgery groups. Using [[HR]]V analysis, the present study compared cardiovascular as well as anthropometric parameters between patients with hip surgery, the hip fracture surgery group (HFS) and the total hip arthroplasty group (THA), and a control group. 71 participants (56.3% women), aged 60-85 years, took part, divided into three groups-patients after hip surgery (21 HFS and 30 THA patients) and a control group (20 participants). Electrocardiogram was recorded at baseline and after the application of a physical stressor (grip strength). A 3 (group) × 2 (time) repeated measures ANOVA, and a chi square test were carried out to test for group differences. Higher weight (p = .002), body mass index (p = .001), and systolic blood pressure (p = .034) were found in THA patients compared to HFS patients. Lower calf circumference (p = .009) and diastolic blood pressure (p = .048) were observed for the HFS group compared to the control group. For cardiovascular parameters, significant differences emerged between the HFS group and the control group in [[HR]] (p = .005), SDNN (p = .034) and SD2 (p = .012). No significant differences in cardiovascular parameters were observed between the two hip surgery groups: neither at baseline nor during stressor recovery. While [[HR]]V seems to differentiate well between HFS patients and controls, more research with larger samples is needed to scrutinize similaritites and differences in cardiovascular profiles between HFS and THA patients.

|keywords=* Aging

* Cardiovascular reactivity

* Heart rate variability

* Hip fracture

* Total hip arthroplasty

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713041

|title=Clinical Role of Lung Ultrasound for the Diagnosis and Prognosis of Coronavirus Disease Pneumonia in Elderly Patients: A Pivotal Study.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33271558

|abstract=Lung ultrasound (LUS) showed a promising role in the diagnosis and monitoring of patients hospitalized for novel coronavirus disease (COVID-19). However, no data are available on its role in elderly patients. The aim of this study was to evaluate the diagnostic and prognostic role of LUS in elderly patients hospitalized for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumonia. Consecutive elderly patients (age >65 years) hospitalized for COVID-19 were enrolled. Demographics, laboratory, comorbidity, and the clinical features of the patients were collected. All patients underwent LUS on admission to the ward. LUS characteristics have been analyzed. Uni- and multivariate analyses to evaluate predictors for in-hospital death were performed. Thirty-seven hospitalized elderly patients (19 men) with a diagnosis of SARS-CoV-2 infection were consecutively enrolled. The median age was 82 years (interquartile range 74.5-93.5). Ultrasound alterations were found in all patients enrolled; inhomogeneous interstitial syndrome with spared areas (91.9%) and pleural alterations (100%) were the most frequent findings. At univariate analysis, LUS score (hazard ratio [[[HR]]] 1.168, 95% CI 1.049-1.301) and pleural effusions ([[HR]] 3.995, 95% CI 1.056-15.110) were associated with in-hospital death. At multivariate analysis, only LUS score ([[HR]] 1.168, 95% CI 1.049-1.301) was independelty associated with in-hospital death. The LUS score's best cutoff for distinguishing patients experiencing in-hospital death was 17 (at multivariate analysis LUS score ≥17, [[HR]] 4.827, 95% CI 1.452-16.040). In-hospital death was significantly different according to the LUS score cutoff of 17 (p = 0.0046). LUS could play a role in the diagnosis and prognosis in elderly patients hospitalized for SARS-CoV-2 infection.

|keywords=* Aging

* Coronavirus disease

* Elderly

* Lung ultrasound

* Severe acute respiratory syndrome-coronavirus-2

|full-text-url=https://sci-hub.do/10.1159/000512209

==ADH5==

|title=Can Serum Nitrosoproteome Predict Longevity of Aged Women?

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33260845

|abstract=Aging is characterized by increase in reactive oxygen (ROS) and nitrogen (RNS) species, key factors of cardiac failure and disuse-induced muscle atrophy. This study focused on serum nitroproteome as a trait of longevity by adopting two complementary gel-based techniques: two-dimensional differential in gel electrophoresis (2-D DIGE) and Nitro-DIGE coupled with mass spectrometry of albumin-depleted serum of aged (A, [i]n[/i] = 15) and centenarian (C, [i]n[/i] = 15) versus young females (Y, [i]n[/i] = 15). Results indicate spots differently expressed in A and C compared to Y and spots changed in A vs. C. Nitro-DIGE revealed nitrosated protein spots in A and C compared to Y and spots changed in A vs. C only ([i]p[/i]-value < 0.01). Nitro-proteoforms of alpha-1-antitripsin (SERPINA1), alpha-1-antichimotripsin (SERPINA3), ceruloplasmin (CP), 13 proteoforms of haptoglobin (HP), and inactive glycosyltransferase 25 family member 3 (CERCAM) increased in A vs. Y and C. Conversely, nitrosation levels decreased in C vs. Y and A, for immunoglobulin light chain 1 (IGLC1), serotransferrin (TF), transthyretin (TTR), and vitamin D-binding protein (VDBP). Immunoblottings of alcohol dehydrogenase 5/S-nitrosoglutathione reductase ([[ADH5]]/GSNOR) and thioredoxin reductase 1 (TRXR1) indicated lower levels of [[ADH5]] in A vs. Y and C, whereas TRXR1 decreased in A and C in comparison to Y. In conclusion, the study identified putative markers in C of healthy aging and high levels of [[ADH5]]/GSNOR that can sustain the denitrosylase activity, promoting longevity.

|keywords=* aging

* cardiovascular disease

* muscle atrophy

* nitrosative stress

* proteomics

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731247

==DCN==

|title=Decorin inhibits the insulin-like growth factor I signaling in bone marrow mesenchymal stem cells of aged humans.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33257596

|abstract=Aging impairs the IGF-I signaling of bone marrow mesenchymal stem cells (bmMSCs), but the mechanism is unclear. Here, we found that the ability to auto-phosphorylate IGF-I receptor (IGF-IR) in response to IGF-I was decreased in the bmMSCs of aged donors. Conversely, data showed that decorin ([[DCN]]) expression was prominently increased in aged bmMSCs, and that under IGF-I treatment, [[DCN]] knockdown in serum-starved aged bmMSCs potentiated their mitogenic activity and IGF-IR auto-phosphorylation, whereas [[DCN]] overexpression in serum-starved adult bmMSCs decreased both activities. Co-immunoprecipitation assays suggested that IGF-I and [[DCN]] bound to IGF-IR in a competitive manner. Online MethPrimer predicted 4 CpG islands (CGIs) in the introns of [i][[DCN]][/i] gene. RT-qPCR and bisulfite sequencing showed that dimethyloxalylglycine, an inhibitor of DNA demethylation, increased [i][[DCN]][/i] mRNA expression and CGI-I methylation in adult bmMSCs, whereas 5-aza-2'-deoxycytidine, a DNA methylation inhibitor, decreased [i][[DCN]][/i] mRNA expression and CGI-I methylation in aged bmMSCs, and ultimately enhanced the proliferation of serum-starved aged bmMSCs under IGF-I stimulation. Thus, IGF-IR could be the prime target of aging in down-regulating the IGF-I signaling of bmMSCs, where [[DCN]] could be a critical mediator.

|keywords=* IGF-I

* aging

* bone marrow mesenchymal stem cell

* osteoporosis

* small leucine-rich proteoglycan

|full-text-url=https://sci-hub.do/10.18632/aging.202166

==HGS==

|title=Handgrip strength asymmetry is associated with future falls in older Americans.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33247424

|abstract=Examining handgrip strength ([[HGS]]) asymmetry could extend the utility of handgrip dynamometers for screening future falls. We sought to determine the associations of [[HGS]] asymmetry on future falls in older Americans. The analytic sample included 10,446 adults aged at least 65 years from the 2006-2016 waves of the Health and Retirement Study. Falls were self-reported. A handgrip dynamometer measured [[HGS]]. The highest [[HGS]] on each hand was used for determining [[HGS]] asymmetry ratio: (non-dominant [[HGS]]/dominant [[HGS]]). Those with [[HGS]] asymmetry ratio < 1.0 had their ratio inverted to make all [[HGS]] asymmetry ratios ≥ 1.0. Participants were categorized into asymmetry groups based on their inverted [[HGS]] asymmetry ratio: (1) 0.0-10.0%, (2) 10.1-20.0%, (3) 20.1-30.0%, and (4) > 30.0%. Generalized estimating equations were used for the analyses. Every 0.10 increase in [[HGS]] asymmetry ratio was associated with 1.26 (95% confidence interval (CI) 1.07-1.48) greater odds for future falls. Relative to those with [[HGS]] asymmetry 0.0-10.0%, participants with [[HGS]] asymmetry > 30.0% had 1.15 (CI 1.01-1.33) greater odds for future falls; however, the associations were not significant for those with [[HGS]] asymmetry 10.1-20.0% (odds ratio: 1.06; CI 0.98-1.14) and 20.1-30.0% (odds ratio: 1.10; CI 0.99-1.22). Compared to those with [[HGS]] asymmetry 0.0-10.0%, participants with [[HGS]] asymmetry > 10.0% and > 20.0% had 1.07 (CI 1.01-1.16) and 1.12 (CI 1.02-1.22) greater odds for future falls, respectively. Asymmetric [[HGS]], as a possible biomarker of impaired neuromuscular function, may help predict falls. We recommend that [[HGS]] asymmetry be considered in [[HGS]] protocols and fall risk assessments.

* Functional laterality

* Geriatric assessment

* Geriatrics

* Muscle strength dynamometer

|full-text-url=https://sci-hub.do/10.1007/s40520-020-01757-z

==MYSM1==

|title=[[MYSM1]] Suppresses Cellular Senescence and the Aging Process to Prolong Lifespan.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33240758

|abstract=Aging is a universal feature of life that is a major focus of scientific research and a risk factor in many diseases. A comprehensive understanding of the cellular and molecular mechanisms of aging are critical to the prevention of diseases associated with the aging process. Here, it is shown that [[MYSM1]] is a key suppressor of aging and aging-related pathologies. [[MYSM1]] functionally represses cellular senescence and the aging process in human and mice primary cells and in mice organs. [[MYSM1]] mechanistically attenuates the aging process by promoting DNA repair processes. Remarkably, [[MYSM1]] deficiency facilitates the aging process and reduces lifespan, whereas [[MYSM1]] over-expression attenuates the aging process and increases lifespan in mice. The functional role of [[MYSM1]] is demonstrated in suppressing the aging process and prolonging lifespan. [[MYSM1]] is a key suppressor of aging and may act as a potential agent for the prevention of aging and aging-associated diseases.

|keywords=* DNA repair

* Myb‐like, SWIRM, and MPN domains‐containing protein 1 (MYSM1)

* aging

* senescence‐associated secretory phenotype (SASP)

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675055

==FOXP1==

|title=GATA6 regulates aging of human mesenchymal stem/stromal cells.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33252174

|abstract=Cellular reprogramming forcing the expression of pluripotency markers can reverse aging of cells but how molecular mechanisms through which reprogrammed cells alter aging-related cellular activities still remain largely unclear. In this study, we reprogrammed human synovial fluid-derived mesenchymal stem cells (MSCs) into induced pluripotent stem cells (iPSCs) using six reprogramming factors and reverted the iPSCs back to MSCs, as an approach to cell rejuvenation. Using the parental and reprogrammed MSCs as control nonrejuvenated and rejuvenated cells, respectively, for comparative analysis, we found that aging-related activities were greatly reduced in reprogrammed MSCs compared with those in their parental lines, indicating reversal of cell aging. Global transcriptome analysis revealed differences in activities of regulatory networks associated with inflammation and proliferation. Mechanistically, we demonstrated that, compared with control cells, the expression of GATA binding protein 6 (GATA6) in reprogrammed cells was attenuated, resulting in an increase in the activity of sonic hedgehog signaling and the expression level of downstream forkhead box P1 ([[FOXP1]]), in turn ameliorating cellular hallmarks of aging. Lower levels of GATA6 expression were also found in cells harvested from younger mice or lower passage cultures. Our findings suggest that GATA6 is a critical regulator increased in aged MSCs that controls the downstream sonic hedgehog signaling and [[FOXP1]] pathway to modulate cellular senescence and aging-related activities.

|keywords=* aging

* cell signaling

* mesenchymal stem cells

* reprogramming

* transcription factors

|full-text-url=https://sci-hub.do/10.1002/stem.3297

==ACE2==

|title=How Does SARS-CoV-2 Affect the Central Nervous System? A Working Hypothesis.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33304284

|abstract=Interstitial pneumonia was the first manifestation to be recognized as caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, in just a few weeks, it became clear that the coronavirus disease-2019 (COVID-19) overrun tissues and more body organs than just the lungs, so much so that it could be considered a systemic pathology. Several studies reported the involvement of the conjunctiva, the gut, the heart and its pace, and vascular injuries such as thromboembolic complications and Kawasaki disease in children and toddlers were also described. More recently, it was reported that in a sample of 214 SARS-CoV-2 positive patients, 36.4% complained of neurological symptoms ranging from non-specific manifestations (dizziness, headache, and seizures), to more specific symptoms such hyposmia or hypogeusia, and stroke. Older individuals, especially males with comorbidities, appear to be at the highest risk of developing such severe complications related to the Central Nervous System (CNS) involvement. Neuropsychiatric manifestations in COVID-19 appear to develop in patients with and without pre-existing neurological disorders. Growing evidence suggests that SARS-CoV-2 binds to the human Angiotensin-Converting Enzyme 2 ([[ACE2]]) for the attachment and entrance inside host cells. By describing [[ACE2]] and the whole Renin Angiotensin Aldosterone System (RAAS) we may better understand whether specific cell types may be affected by SARS-CoV-2 and whether their functioning can be disrupted in case of an infection. Since clear evidences of neurological interest have already been shown, by clarifying the topographical distribution and density of [[ACE2]], we will be able to speculate how SARS-CoV-2 may affect the CNS and what is the pathogenetic mechanism by which it contributes to the specific clinical manifestations of the disease. Based on such evidences, we finally hypothesize the process of SARS-CoV-2 invasion of the CNS and provide a possible explanation for the onset or the exacerbation of some common neuropsychiatric disorders in the elderly including cognitive impairment and Alzheimer disease.

* Alzheimer disease

* Ang(1-7)/Mas

* COVID-19

* neurodegenerative and psychiatric disorders abstract

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701095

|title=Effects of Age on Inflammatory Profiles and Nutrition/Energy Metabolism in Domestic Cats.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33262938

|abstract=Animals tend to increase in body weight and body condition score (BCS) with aging. Serum diagnostic markers related to energy metabolism may show changes even in healthy cats with aging. Seventy domestic cats were recruited for this study. Based upon the modified AAFP-AAHA Feline Life Stage Guidelines, animals were divided into six groups: Junior (7 months-2 years), Prime (3 -6 years), Mature (7-10 years), Senior (11-14 years), Geriatric-obese (15 years ≤) and Geriatric-thin (15 years ≤). Their body condition scores (BCS) ranged from 3/9 to 9/9. Changes in metabolites, inflammatory markers, hormone concentrations and enzyme activities related to energy metabolism were investigated in serum of 70 domestic cats of various ages. Serum glucose (GLU) concentrations in the Mature, Senior, and Geriatric-obese groups were significantly higher than those in the Junior group. Serum amyloid A (SAA) concentrations in the Geriatric-thin group were significantly increased compared with the Junior group. SAA concentrations in the Geriatric-obese group tended to increase although there were no statistically significant differences. In the Mature, Senior, Geriatric-obese and Geriatric-thin groups, malate dehydrogenase/lactate dehydrogenase (M/L) ratio, an energy metabolic indicator, tended to decrease compared with the Junior group. In the Senior group, triglyceride (TG) concentrations were significantly increased compared with the Junior group. In the Geriatric-obese and Geriatric-thin groups, blood urea nitrogen (BUN) concentrations were significantly increased compared with the Junior group. In the Geriatric-obese group, albumin ([[ALB]]) concentrations were decreased compared with the Junior group. Aged domestic cats tend to increase in body weight and BCS. In addition, serum GLU, TG, SAA, and BUN concentrations increased and serum [[ALB]] concentrations and M/L ratio decreased. These diagnostic markers may be useful to detect small changes related to energy metabolism with aging that may cause obesity with light inflammation in healthy cats.

|keywords=* M/L ratio

* SAA

* aging

* domestic cats

* obesity

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695597

==TRIM27==

|title=[[TRIM27]] Functions as a Novel Oncogene in Non-Triple-Negative Breast Cancer by Blocking Cellular Senescence through p21 Ubiquitination.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33251042

|abstract=In the current study, we aimed to explore the correlation between [[TRIM27]] and breast cancer prognosis, as well as the functions of [[TRIM27]] in breast cancer and their underlying mechanisms. Bioinformatics analyses were used to examine the correlation between [[TRIM27]] and breast cancer prognosis. Moreover, [[TRIM27]] knockdown and overexpression in breast cancer cells were performed to investigate its functions in breast cancer. Tamoxifen (TAM) was applied to evaluate the influence of [[TRIM27]] on chemoresistance of breast cancer cells, while co-immunoprecipitation (coIP) was performed to identify the E3 ubiquitin ligase capability of [[TRIM27]]. High expression of [[TRIM27]] was found in non-triple-negative breast cancer (non-TNBC) tumor tissues and was positively correlated with the mortality of non-TNBC patients. Moreover, [[TRIM27]] could suppress non-TNBC cell apoptosis and senescence, promote cell viability and tumor growth, counteract the anti-cancer effects of TAM, and mediate ubiquitination of p21. In addition, EP300 could enhance the expression of [[TRIM27]] and its transcription promoter H3K27ac. [[TRIM27]], through ubiquitination of p21, might serve as a prognostic biomarker for non-TNBC prognosis. [[TRIM27]] functions as a novel oncogene in non-TNBC cellular processes, especially suppressing cell senescence and interfering with non-TNBC chemoresistance.

|keywords=* EP300

* TRIM27

* breast cancer

* cell apoptosis

* cell senescence

* chemoresistance

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666371

 

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33266358

|abstract=Frailty is a geriatric syndrome represented by susceptibility to precipitating health events and reduced functional reserve. Frailty can be difficult to measure in clinical practice and research. One approach to approximate frailty is based on a deficit accumulation approach, which assesses a larger number of less specific measures such as the presence of comorbidities, physical or cognitive assessments, and lab tests, and summarizes these as a frailty index. The objective of this study was to develop such an index using the Lifestyle Interventions and Independence for Elders (LIFE) Study and evaluate the validity of the frailty measure derived based on baseline information via its association with the primary outcomes of the trial, namely major mobility disability ([[MMD]]) and persistent [[MMD]] (p[[MMD]]). Further, this study aimed to evaluate the effectiveness of the physical activity intervention among participants based on their baseline frailty score. Subjects in the LIFE Study were evaluated at baseline for demographics, clinical history, and a battery of physical and cognitive functioning assessments. In total, 75 possible deficits were scored either as present (yes/no) or based on each score's quintiles for score-based assessments. The frailty index was measured as the total sum of deficits divided by the total number of possible deficits on a continuous scale between 0 and 100 (i.e., percent of deficits present). The frailty index was further divided into quintiles for comparison. A proportional hazards model was estimated for the [[MMD]] outcome controlling for other baseline information. A data driven approach was also used to determine relevant cut-offs in the frailty index where the trial intervention appeared to be modified. Among 1635 trial participants, the mean frailty index was 30.4 ± 6.6 and normally distributed. Over 2.5 years of average follow-up, 14.6%, 16.5%, 18.6%, 22.6%, and 27.6% of participants experienced [[MMD]] in quintiles 1-5, respectively. Each 1-unit increase in the frailty index increased the hazard of [[MMD]] by 4% (2-5%), and there was a nearly 2-fold increase in [[MMD]] between the highest and lowest frailty quintiles. Using log-rank criteria, a cut-point at the median was identified. Further, iterations tested for a frailty cut-off and indicated a subgroup beyond the 85th percentile wherein the physical activity intervention appeared to be no longer be effective. This internally derived deficit accumulation frailty index was uniquely able to identify individuals at higher risk of [[MMD]] and p[[MMD]] and showed that along the spectrum of frailty, the physical activity intervention remained effective for the majority of participants.

 

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700674

==TPH1==

|title=[i]Lactobacillus plantarum[/i] DR7 improved brain health in aging rats via the serotonin, inflammatory and apoptosis pathways.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33245015

|abstract=Aging processes affect the brain in many ways, ranging from cellular to functional levels which lead to cognitive decline and increased oxidative stress. The aim of this study was to investigate the potentials of [i]Lactobacillus plantarum[/i] DR7 on brain health including cognitive and memory functions during aging and the impacts of high fat diet during a 12-week period. Male Sprague-Dawley rats were separated into six groups: (1) young animals on normal diet (ND, (2) young animals on a high fat diet (HFD), (3) aged animals on ND, (4) aged animals on HFD, (5) aged animals on HFD and [i]L. plantarum[/i] DR7 (10  cfu/day) and (6) aged animals receiving HFD and lovastatin. To induce ageing, all rats in group 3 to 6 were injected sub-cutaneously at 600 mg/kg/day of D-galactose daily. The administration of DR7 has reduced anxiety accompanied by enhanced memory during behavioural assessments in aged-HFD rats ([i]P[/i]<0.05). Hippocampal concentration of all three pro-inflammatory cytokines were increased during aging but reduced upon administration of both statin and DR7. Expressions of hippocampal neurotransmitters and apoptosis genes showed reduced expressions of indoleamine dioxygenase and P53 accompanied by increased expression of [[TPH1]] in aged- HFD rats administered with DR7, indicating potential effects of DR7 along the pathways of serotonin and oxidative senescence. This study provided an insight into potentials of [i]L. plantarum[/i] DR7 as a prospective dietary strategy to improve cognitive functions during aging. This study provided an insight into potentials of [i]L. plantarum[/i] DR7 as a prospective dietary strategy to improve cognitive functions during aging.

|keywords=* Lactobacillus spp.

* aging

* brain

|full-text-url=https://sci-hub.do/10.3920/BM2019.0200

==LMNB1==

|title=Cellular senescence as a response to multiwalled carbon nanotube (MWCNT) exposure in human mesothelial cells.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33279583

|abstract=Cellular senescence is a stable cell cycle arrest induced by diverse triggers, including replicative exhaustion, DNA damaging agents, oncogene activation, oxidative stress, and chromatin disruption. With important roles in aging and tumor suppression, cellular senescence has been implicated also in tumor promotion. Here we show that certain multiwalled carbon nanotubes (MWCNTs), as fiber-like nanomaterials, can trigger cellular senescence in primary human mesothelial cells. Using in vitro approaches, we found manifestation of several markers of cellular senescence, especially after exposure to a long and straight MWCNT. These included inhibition of cell division, senescence-associated heterochromatin foci, senescence-associated distension of satellites, [[LMNB1]] depletion, γH2A.X nuclear panstaining, and enlarged cells exhibiting senescence-associated β-galactosidase activity. Furthermore, genome-wide transcriptome analysis revealed many differentially expressed genes, among which were genes encoding for a senescence-associated secretory phenotype. Our results clearly demonstrate the potential of long and straight MWCNTs to induce premature cellular senescence. This finding may find relevance in risk assessment of workplace safety, and in evaluating MWCNT's use in medicine such as drug carrier, due to exposure effects that might prompt onset of age-related diseases, or even carcinogenesis.

|keywords=* alpha tubulin

* cellular senescence

* mesothelial cells

* microarray analysis

* multiwalled carbon nanotubes

|full-text-url=https://sci-hub.do/10.1016/j.mad.2020.111412

|title=SIRT1 - a new mammalian substrate of nuclear autophagy.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33292048

|abstract=Macroautophagic/autophagic degradation of nuclear components (or nuclear autophagy) is a poorly understood area in autophagy research. We previously reported the nuclear lamina protein [[LMNB1]] (lamin B1) as a nuclear autophagy substrate in primary human cells, stimulating the investigation of nuclear autophagy in the mammalian system. We recently reported the sirtuin protein SIRT1 as a new selective substrate of nuclear autophagy in senescence and aging. Upon senescence of primary human cells, SIRT1 degradation is mediated by a direct nuclear SIRT1-LC3 interaction, followed by nucleus-to-cytoplasm shuttling of SIRT1 and autophagosome-lysosome degradation. In vivo, SIRT1 is downregulated by lysosomes in hematopoietic and immune organs upon natural aging in mice and in aged human T cells. Our study identified another substrate of nuclear autophagy and suggests a new strategy to promote SIRT1-mediated health benefits by suppressing its autophagic degradation.

|keywords=* Aging

* SIRT1

* nuclear autophagy

* senescence

* sirtuin

|full-text-url=https://sci-hub.do/10.1080/15548627.2020.1860541

==TNF==

|title=Naringenin alleviates nonalcoholic steatohepatitis in middle-aged Apoe mice: role of SIRT1.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33234364

|abstract=Naringenin is naturally isolated from citrus fruits possessing many pharmacological activities. However, little is known about the effect of naringenin on nonalcoholic steatohepatitis (NASH) in the model of metabolic syndrome. The present study is aimed to investigate the effect of naringenin on NASH in 12-mo-old male ApoE  mice and its possible underlying mechanism. In vivo, 12-mo-old male ApoE  mice were administrated with naringenin by intragastric gavage for 12 weeks. At the end of experiment, the blood samples and liver tissues were collected. Metabolic parameters in serum, levels of triglyceride, cholesterol and hydroxyproline, activities of antioxidant enzymes, and content of inflammatory cytokines ([[TNF]]-α and IL-6) in liver were examined by corresponding assay kits. Pathological changes in liver were observed by hematoxylin-eosin, oil red O, masson's trichrome, picro-sirius red and senescence β-galactosidase staining. Dihydroethidium was used for detection of reactive oxygen species (ROS). In vitro, AML-12 cells were treated with oleic acid in the presence or absence of naringenin for 24 h. Transfection of SIRT1 siRNA was also conducted in vitro. Lipid accumulation, cellular ROS generation, malondialdehyde content, antioxidant enzyme activities and secretion levels of [[TNF]]-α and IL-6 were examined. Both in vivo and in vitro, gene expressions were detected by real-time PCR or western blot. Naringenin administration improved metabolic parameters, suppressed hepatic steatosis, regulated expression of genes involved in lipid metabolism (FASN, SCD1, PPARα and CPT1α), reduced hepatic fibrosis and cell senescence, inhibited hepatic inflammation as evidenced by the decreased macrophage recruitment and content of [[TNF]]-α and IL-6, and reduced hepatic oxidative stress by suppressing ROS generation and normalizing activities of antioxidant enzymes. Notably, naringenin administration increased hepatic SIRT1 protein expression and activity along with the increased deacetylation of liver kinase B1 (LKB1), PGC1α and NF-κB. In vitro study, the benefits of naringenin on lipid accumulation, oxidative stress and inflammation were diminished by SIRT1 siRNA transfection. These results indicate that naringenin administration may be a potential curative therapy for NASH treatment and the activation of hepatic SIRT1-mediated signaling cascades is involved in its beneficial effects.

|keywords=* AML-12 cells

* Aging

* ApoE(−/−) mice

* Naringenin

* Nonalcoholic steatohepatitis

* SIRT1

|full-text-url=https://sci-hub.do/10.1016/j.phymed.2020.153412

==NPR1==

|title=The [[NPR1]]-WRKY46-WRKY6 signaling cascade mediates probenazole/salicylic acid-elicited leaf senescence in Arabidopsis thaliana.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33270345

|abstract=Endogenous salicylic acid (SA) regulates leaf senescence, but the underlying mechanism remains largely unexplored. The exogenous application of SA to living plants is not efficient for inducing leaf senescence. By taking advantage of probenazole (PBZ)-induced biosynthesis of endogenous SA, we previously established a chemical inducible leaf senescence system that depends on SA biosynthesis and its core signaling receptor [[NPR1]] in Arabidopsis thaliana. Here, using this system, we identified WRKY46 and WRKY6 as key components of the transcriptional machinery downstream of [[NPR1]] signaling. Upon PBZ treatment, the wrky46 mutant exhibited significantly delayed leaf senescence. We demonstrate that [[NPR1]] is essential for PBZ/SA-induced WRKY46 activation, whereas WRKY46 in turn enhances [[NPR1]] expression. WRKY46 interacts with [[NPR1]] in the nucleus, binding to the W-box of the WRKY6 promoter to induce its expression in response to SA signaling. Dysfunction of WRKY6 abolished PBZ-induced leaf senescence, while overexpression of WRKY6 was sufficient to accelerate leaf senescence even under normal growth conditions, suggesting that WRKY6 may serve as an integration node of multiple leaf senescence signaling pathways. Taken together, these findings reveal that the [[NPR1]]-WRKY46-WRKY6 signaling cascade plays a critical role in PBZ/SA-mediated leaf senescence in Arabidopsis. This article is protected by copyright. All rights reserved.

|keywords=* Leaf senescence

* NPR1

* Probenazole

* Salicylic acid

* WRKY46

* WRKY6

|full-text-url=https://sci-hub.do/10.1111/jipb.13044

==NLRP3==

|title=Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33269094

|abstract=The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, myeloid cells and [[NLRP3]] inflammasome, declined levels of NK cells in innate immunity, thymus involution and decreased amount of naive T-cells in adaptive immunity, are biomarkers of aging and predisposition factors for cellular senescence and aging-related pathologies. Long-living species, human centenarians, and women are characterized by less inflamm-aging and decelerated immunosenescence. Despite recent progress in understanding, the harmonious theory of immunosenescence is still developing. Geroprotectors targeting these mechanisms are just emerging and are comprehensively discussed in this article.

|keywords=* adaptive immunity

* innate immunity

* longevity

* resilience

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673842

==CCK==

|title=Senolytic agent Quercetin ameliorates intervertebral disc degeneration via the Nrf2/NF-κB axis.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33242601

|abstract=Intervertebral disc degeneration (IDD) represents major cause of low back pain. Quercetin (QUE) is one of the approved senolytic agents. In this study, we evaluated the protective effects of QUE on IDD development and its underlying mechanism. Effects of senolytic agent QUE on the viability of nucleus pulposus cells (NPCs) were measured by [[CCK]]-8 assays and EdU staining. The senescence associated secreted phenotype (SASP) factors expressions were measured by qPCR, western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and western blot. Molecular docking was applied to predict the interacting protein of QUE; while Nrf2 was knocked down by siRNAs to confirm its role in QUE regulated senescence phenotype. X-ray, MRI, Hematoxylin-Eosin and Safranin O-Fast green staining were performed to evaluate the therapeutic effects of QUE on IDD in the puncture-induced rat model. In in vitro experiments, QUE inhibited SASP factors expression and senescence phenotype in IL-1β-treated NPCs. Mechanistically, QUE suppressed IL-1β induced activation of the NF-κB pathway cascades; it was also demonstrated in molecular docking and knock down studies that QUE might bind to Keap1-Nrf2 complex to suppress NF-κB pathway. In vivo, QUE ameliorated the IDD process in the puncture-induced rat model. Together the present work suggests that QUE inhibits SASP factors expression and senescence phenotype in NPCs and ameliorates the progression of IDD via the Nrf2/NF-κB axis, which supports senolytic agent QUE as a potential therapeutic agent for the treatment of IDD.

|keywords=* Intervertebral disc degeneration

* NF-κB pathway

* Nrf2

* Quercetin

* Senescence

|full-text-url=https://sci-hub.do/10.1016/j.joca.2020.11.006

==RPE==

|title=Transcriptomic Profiling of Human Pluripotent Stem Cell-derived Retinal Pigment Epithelium over Time.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33307245

|abstract=Human pluripotent stem cell (hPSC)-derived progenies are immature versions of cells, presenting a potential limitation to the accurate modelling of diseases associated with maturity or age. Hence, it is important to characterise how closely cells used in culture resemble their native counterparts. In order to select appropriate time points of retinal pigment epithelium ([[RPE]]) cultures that reflect native counterparts, we characterised the transcriptomic profiles of the hPSC-derived [[RPE]] cells from 1- and 12-month cultures. We differentiated the human embryonic stem cell line H9 into [[RPE]] cells, performed single-cell RNA-sequencing of a total of 16,576 cells to assess the molecular changes of the [[RPE]] cells across these two culture time points. Our results indicate the stability of the [[RPE]] transcriptomic signature, with no evidence of an epithelial-mesenchymal transition, and with the maturing populations of the [[RPE]] observed with time in culture. Assessment of Gene Ontology pathways revealed that as the cultures age, [[RPE]] cells upregulate expression of genes involved in metal binding and antioxidant functions. This might reflect an increased ability to handle oxidative stress as cells mature. Comparison with native human [[RPE]] data confirms a maturing transcriptional profile of [[RPE]] cells in culture. These results suggest that long-term in vitro culture of [[RPE]] cells allows the modelling of specific phenotypes observed in native mature tissues. Our work highlights the transcriptional landscape of hPSC-derived [[RPE]] cells as they age in culture, which provides a reference for native and patient samples to be benchmarked against.

* Human embryonic stem cell

* Human pluripotent stem cell

* Retinal pigment epithelium

* Single-cell RNA sequencing

|full-text-url=https://sci-hub.do/10.1016/j.gpb.2020.08.002

==FES==

|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

==CPNE1==

|title=Prevalent intron retention fine-tunes gene expression and contributes to cellular senescence.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33274830

|abstract=Intron retention (IR) is the least well-understood alternative splicing type in animals, and its prevalence and function in physiological and pathological processes have long been underestimated. Cellular senescence contributes to individual aging and age-related diseases and can also serve as an important cancer prevention mechanism. Dynamic IR events have been observed in senescence models and aged tissues; however, whether and how IR impacts senescence remain unclear. Through analyzing polyA  RNA-seq data from human replicative senescence models, we found IR was prevalent and dynamically regulated during senescence and IR changes negatively correlated with expression alteration of corresponding genes. We discovered that knocking down (KD) splicing factor U2AF1, which showed higher binding density to retained introns and decreased expression during senescence, led to senescence-associated phenotypes and global IR changes. Intriguingly, U2AF1-KD-induced IR changes also negatively correlated with gene expression. Furthermore, we demonstrated that U2AF1-mediated IR of specific gene ([[CPNE1]] as an example) contributed to cellular senescence. Decreased expression of U2AF1, higher IR of [[CPNE1]], and reduced expression of [[CPNE1]] were also discovered in dermal fibroblasts with age. We discovered prevalent IR could fine-tune gene expression and contribute to senescence-associated phenotypes, largely extending the biological significance of IR.

|keywords=* CPNE1

* U2AF1

* intron retention

* splicing factor

|full-text-url=https://sci-hub.do/10.1111/acel.13276

==SIRT6==

|title=Association between [[SIRT6]] Methylation and Human Longevity in a Chinese Population.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33238266

|abstract=Sirtuin 6 gene ([[SIRT6]]) is a longevity gene that is involved in a variety of metabolic pathways, but the relationship between [[SIRT6]] methylation and longevity has not been clarified. We conducted a case-control study on 129 residents with a family history of longevity (1 of parents, themselves, or siblings aged ≥90 years) and 86 individuals without a family history of exceptional longevity to identify the association. DNA pyrosequencing was performed to analyze the methylation status of [[SIRT6]] promoter CpG sites. qRT-PCR and ELISA were used to estimate the [[SIRT6]] messenger RNA (mRNA) levels and protein content. Six CpG sites (P1-P6) were identified as methylation variable positions in the [[SIRT6]] promoter region. At the P2 and P5 CpG sites, the methylation rates of the longevity group were lower than those of the control group (p < 0.001 and p = 0.009), which might be independent determinants of longevity. The mRNA and protein levels of [[SIRT6]] decreased in the control group (p < 0.0001 and p = 0.038). The mRNA level negatively correlated with the methylation rates at the P2 (rs = -0.173, p = 0.011) and P5 sites (rs = -0.207, p = 0.002). Furthermore, the protein content positively correlated with the methylation rate at the P5 site (rs = 0.136, p = 0.046) but showed no significant correlation with the methylation rate at the P2 site. The low level of [[SIRT6]] methylation may be a potential protective factor of Chinese longevity.

|keywords=* DNA Methylation

* Longevity

* Messenger RNA

* SIRT6

|full-text-url=https://sci-hub.do/10.1159/000508832

==P2RY12==

|title=Potential caveats of putative microglia-specific markers for assessment of age-related cerebrovascular neuroinflammation.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33261619

|abstract=The ability to distinguish resident microglia from infiltrating myeloid cells by flow cytometry-based surface phenotyping is an important technique for examining age-related neuroinflammation. The most commonly used surface markers for the identification of microglia include CD45 (low-intermediate expression), CD11b, Tmem119, and [[P2RY12]]. In this study, we examined changes in expression levels of these putative microglia markers in in vivo animal models of stroke, cerebral amyloid angiopathy (CAA), and aging as well as in an ex vivo LPS-induced inflammation model. We demonstrate that Tmem119 and [[P2RY12]] expression is evident within both CD45  and CD45  myeloid populations in models of stroke, CAA, and aging. Interestingly, LPS stimulation of FACS-sorted adult microglia suggested that these brain-resident myeloid cells can upregulate CD45 and downregulate Tmem119 and [[P2RY12]], making them indistinguishable from peripherally derived myeloid populations. Importantly, our findings show that these changes in the molecular signatures of microglia can occur without a contribution from the other brain-resident or peripherally sourced immune cells. We recommend future studies approach microglia identification by flow cytometry with caution, particularly in the absence of the use of a combination of markers validated for the specific neuroinflammation model of interest. The subpopulation of resident microglia residing within the "infiltrating myeloid" population, albeit small, may be functionally important in maintaining immune vigilance in the brain thus should not be overlooked in neuroimmunological studies.

* Brain infiltrating myeloid cells

* CD45

* Cerebral amyloid angiopathy

* Microglia

* Neuroinflammation

* P2RY12

* Tmem119

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709276

==CXCL14==

|title=Identification of genes associated with endometrial cell aging.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33258951

|abstract=Aging of the uterine endometrium is a critical factor that affects reproductive success, but the mechanisms associated with uterine aging are unclear. In this study, we conducted a qualitative examination of age-related changes in endometrial tissues and identified candidate genes as markers for uterine aging. Gene expression patterns were assessed by two RNA sequencing experiments using uterine tissues from wild type (WT) C57BL/6 mice. Gene expression data obtained by RNA-sequencing were validated by real-time PCR. Genes expressing the pro-inflammatory cytokines Il17rb and chemokines Cxcl12 and Cxcl14 showed differential expression between aged WT mice and a group of mice composed of 5 and 8 week-old WT (young) animals. Protein expression levels of the above-mentioned genes and of IL8, which functions downstream of IL17RB, were analysed by quantitative immunohistochemistry of unaffected human endometrium tissue samples from patients in their 20 s and 40 s (10 cases each). In the secretory phase samples, 3,3'- diaminobenzidine (DAB) staining intensities of IL17RB, CXCL12 and [[CXCL14]] for patients in their 40 s were significantly higher than that for patients in their 20 s, as detected by a Mann Whitney U test. These results suggest that these genes are candidate markers for endometrial aging and for prediction of age-related infertility, although confirmation of these findings is needed in larger studies involving fertile and infertile women.

|keywords=* CXCL12

* CXCL14

* IL17RB

* endometrial cell aging

* infertility

* quantitative

|full-text-url=https://sci-hub.do/10.1093/molehr/gaaa078

==RNF10==

|title=Reduced RING finger protein 10 expression in macrophages is associated with aging-related inflammation.

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33249776

|abstract=Age-associated decline of the immune system is referred to as immunosenescence. The E3 ligase RING finger 10 ([[RNF10]]) has long been associated with the innate immune response, but a potential role in immunosenescence has not previously been reported. In the present study, we identified that [[RNF10]] expression is lower in aged mouse macrophages than in young cells. After lipopolysaccharide (LPS) stimulation, [[RNF10]] expression remained at a basal low level in aged mouse cells, but declined sharply in young mouse cells. Knockdown of [[RNF10]] enhanced both the nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) signaling pathways and thus enhanced proinflammatory cytokines and type I interferons (IFN-I) in macrophages, promoting clearance of L. monocytigenes. These findings indicate that dysregulated expression of [[RNF10]] is associated with age-associated immune dysfunction, and [[RNF10]] may thus be a potential target for the treatment of age-related inflammatory diseases.

|keywords=* E3 ubiquitin ligase

* RNF10

* immunosenescence

* inflammation

* macrophages

|full-text-url=https://sci-hub.do/10.1002/2211-5463.13049

==GC==

|title=Body Size and Cuticular Hydrocarbons as Larval Age Indicators in the Forensic Blow Fly, Chrysomya albiceps (Diptera: Calliphoridae).

|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33274739

|abstract=Chrysomya albiceps (Wiedemann 1819) is one of the most important insects in forensic entomology. Its larval developmental and survival rates are influenced by nutritional resources, temperature, humidity, and geographical regions. The present study investigated the possibility of relying on body size and cuticular hydrocarbon composition as indicators for age estimation of the different larval instars of C. albiceps. Larvae were maintained in standardized laboratory conditions at different experimental temperatures. All larval instars (first, second, and third) were randomly collected for measuring their body sizes and for estimating their cuticular hydrocarbons at different rearing temperatures (30, 35, 40, and 45°C) using gas chromatography-mass spectrometry ([[GC]]-MS). Results indicated that the duration of larval stage was temperature dependent as it gradually decreased on increasing the rearing temperature (30, 35, and 40°C) except 45°C at which larval development was ceased. In contrary, larval body size, in terms of length, width, and weight, was temperature dependent as it gradually increased with larval development on increasing rearing temperature except at 45°C at which larval development was ceased. The [[GC]]-MS showed a significant difference in the extracted components of cuticular hydrocarbons between different larval instars reared in the same temperature and between the same larval instar that reared at different temperatures. Furthermore, the highest and lowest amounts of cuticular hydrocarbons were detected at 35 and 40°C, respectively. Overall, larval body size and cuticular hydrocarbon components were temperature dependent within the range 30-40°C, which may suggest them as possible reliable age indicators for estimating the postmortem interval in the field of medicolegal entomology.