Редактирование: CXCL10 (раздел)

==Publications==

{{medline-entry
|title=Age-related decline of interferon-gamma responses in macrophage impairs satellite cell proliferation and regeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32725722
|abstract=Impaired muscle regeneration and increased muscle fibrosis are observed in aged muscle accompanied by progressive loss of muscle mass (sarcopenia). However, the underlying mechanism is still unclear. The differentiated expressed genes in young and aged muscles after acute injury by cardiotoxin were identified by RNA-sequence analysis. Single-cell RNA-sequence analysis was used to identify cell clusters and functions in young muscle after acute injury, and flow cytometry analysis and sorting were used to validate the function. The proliferation and differentiation functions of satellite cells were accessed by immunostaining with 5-ethynyl-2'-deoxyuridine and embryonic myosin heavy chain (eMyHC), respectively. Muscle regeneration ability was accessed by histopathological and molecular biological methods. Gene expression patterns associated with responses to interferon-gamma (IFN-γ) (15 genes; false discovery rate < 0.001) were significantly down-regulated during muscle regeneration in aged mice (P = 2.25e-7). CD8  T cells were the main source of increased IFN-γ after injury, adoptive transfer of wild-type CD8  T cells to IFN-γ-deficient young mice resulted in 78% increase in cross-sectional areas (CSAs) of regenerated myofibres (P < 0.05) and 63% decrease in muscle fibrosis (P < 0.05) after injury. Single-cell RNA-sequence analysis identified a novel subset of macrophages [named as IFN-responsive macrophages (IFNRMs)] that specifically expressed IFN-responsive genes (Ifit3, Isg15, Irf7, etc.) in young mice at 3 days after injury, and the number of this macrophage subset was ~20% lower in aged mice at the same time (P < 0.05). IFNRMs secreted cytokine C-X-C motif chemokine 10 ([[CXCL10]]) that promoted the proliferation and differentiation of satellite cells via its receptor, [[CXCR3]]. Intramuscular recombinant [[CXCL10]] treatment in aged mice rejuvenated the proliferation of satellite cells (80% increase in Ki-67  Pax7  cells, P < 0.01) and resulted in 27% increase in CSA of regenerated myofibres (P < 0.01) and 29% decrease in muscle fibrosis (P < 0.05). Our study indicates that decline in IFN-γ response in a novel subset of macrophage contributes to satellite cells dysfunctions in aged skeletal muscles and demonstrates that this mechanism can be targeted to restore age-associated myogenesis.

|keywords=* Aging
* CXCL10
* IFN-γ
* Macrophage
* Muscle regeneration
* Single-cell RNA sequence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567146
}}
{{medline-entry
|title=[[CXCL9]] and [[CXCL10]] display an age-dependent profile in Chagas patients: a cohort study of aging in Bambui, Brazil.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32393333
|abstract=Chagas disease is endemic in Latin America and still represents an important public health problem in the region. Chronic cardiomyopathy is the most significant chronic form due to its association with morbidity and mortality. The last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage, with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune response. Although studies have evaluated the role of chemokines in experimental T. cruzi infection, few have addressed their systemic profile, especially for human infection and in aging populations. The present work aimed to use the data from a large population based study of older adults, conducted in an endemic area for Chagas disease, to examine the association between serum levels of cytokines and chemokines, T. cruzi infection and electrocardiogram (ECG) abnormality. The present work evaluated serum levels of [[CCL2]], [[CXCL9]], [[CXCL10]], [[CCL5]], [[CXCL8]], IL-1β, IL-6, [[TNF]], IL-12 and IL-10 by Flow Cytometric Bead Array assay (CBA) and the results expressed in pg/ml. The baseline survey started in January 1st 1997, with 1284 participants of an aged population-based cohort. Participants signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records verification. Our results demonstrated that Chagas disease patients had higher serum levels of [[CXCL9]], [[CXCL10]] and IL-1β and lower serum levels of [[CCL5]] than non-infected subjects. Moreover, our data demonstrated that [[CXCL9]] and [[CXCL10]] increased in an age-dependent profile in Chagas disease patients. Together, this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Biomarkers
* Brazil
* Chagas Disease
* Chemokine CXCL10
* Chemokine CXCL9
* Cohort Studies
* Electrocardiography
* Female
* Humans
* Male
* Middle Aged
* Trypanosoma cruzi
|keywords=* Chagas disease
* Chemokines
* Cohort
* Cytokines
* Immune biomarkers
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216412
}}
{{medline-entry
|title=p53 and p53-related mediators PAI-1 and IGFBP-3 are downregulated in peripheral blood mononuclear cells of HIV-patients exposed to non-nucleoside reverse transcriptase inhibitors.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32272174
|abstract=The improved effectiveness and safety of the combined antiretroviral therapy (cART) has largely diminished mortality and AIDS-defining morbidity of HIV-patients. Nevertheless, chronic age-related diseases in these individuals are more common and their underlying pathogenic mechanisms of these actions seem to involve accelerated aging and enhanced inflammation. The present study explores markers of these processes in a heterogenous Spanish HIV cohort using peripheral blood samples of HIV-patients and matched uninfected controls. We isolated periheral blood mononuclear cells (PBMCs) and i) compared the expression of a panel of 14 genes related to inflammation and senescence in PBMCs of HIV-patients vs matched uninfected controls, ii) analyzed the expression in HIV-patients in association with a number of demographic, biochemical and immunological parameters and iii) in relation with the current cART they received. PBMCs of HIV-patients displayed significantly increased expression of general inflammatory genes ([[IL6]], [[IL18]] and [[CXCL10]]) and this occurs irrespectively of the antiviral therapy they have been receiving. Conversely, levels of senescence-associated genes [[TP53]], [[SERPINE1]]andIGFBP3 were slightly but significantly reduced in patients compared to uninfected matched individuals and this effect is related to NNRTI-containing treatments. The expression of the inflammatory markers [[IL6]], [[IL18]], [[IL1B]], TNFA, [[RELA]], [[CCL2]], [[[[CCL2]]0]] and [[CXCL10]] displayed correlation with certain demographic, morbidity- and HIV infection-related parameters. The levels of [[TP53]] mRNA were positively associated only with plasma LDL. Correlation analysis between the expressions of pairs of genes revealed a different pattern between HIV-patients and controls. The diminished expression of [[TP53]] and [[SERPINE1]] in HIV-patients was also observed at a protein level, and the correlation between the two proteins (p53 and PAI1) in patients and controls showed the opposite trend. In conclusion, HIV-patients show dysregulation of p53 and p53-related mediators, a phenomenon which may be of pathophysiological relevance and could be related to the shorter health- and/or life-span observed in these individuals.

|keywords=* Aging
* Antiretroviral drugs
* HIV
* Inflammation
* NNRTI
* Senescence
* p53
|full-text-url=https://sci-hub.do/10.1016/j.antiviral.2020.104784
}}
{{medline-entry
|title=Transcriptomic and functional studies reveal undermined chemotactic and angiostimulatory properties of aged microglia during stroke recovery.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32065074
|abstract=Age-dependent alterations in microglia behavior have been implicated in neurodegeneration and CNS injuries. Here, we compared the transcriptional profiles of young versus aged microglia during stroke recovery. CD45 CD11b  microglia were FACS-isolated from the brains of young (10-week-old) and aged (18-month-old) male mice with sham operation or 14 days after distal middle cerebral artery occlusion and subjected to RNA-sequencing analysis. Functional groups enriched in young microglia are indicative of upregulation in cell movement, cell interactions, inflammatory responses and angiogenesis, while aged microglia exhibited a reduction or no change in these features. We confirmed reduced chemoattractive capacities of aged microglia toward ischemic brain tissue in organotypic slide co-cultures, and delayed accumulation of aged microglia around dead neurons injected into the striatum [i]in vivo[/i]. In addition, aging is associated with an overall failure to increase the expression of microglial genes involved in cell-cell interactions, such as [[CXCL10]]. Finally, impaired upregulation of pro-angiogenic genes in aged microglia was associated with a decline in neovascularization in aged mice compared to young mice after distal middle cerebral artery occlusion. This study provides a new resource to understand the mechanisms underlying microglial alterations in the aged brain milieu and sheds light on new strategies to improve microglial functions in aged stroke victims.

|keywords=* Microglia
* aging
* angiogenesis
* cell movement
* transcriptome
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687033
}}
{{medline-entry
|title=Neuroprotective effects of targeting BET proteins for degradation with dBET1 in aged mice subjected to ischemic stroke.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30872008
|abstract=Neuroinflammation after stroke significantly contributes to neuronal cell death. Bromodomain and Extra Terminal Domain (BET) proteins are essential to inflammatory gene transcription. BET proteins (BRD2, [[BRD3]], [[BRD4]], and BRDT) have varied effects including chromatin remodeling, histone acetyltransferase activity, and as scaffolds to recruit transcription factors; they couple chromatin remodeling with transcription. BRD2/4 are of particularly interest to stroke-induced neuroinflammation that contributes to delayed cell death as they are required for NF-κB-dependent gene transcription. We hypothesized that targeting BET proteins for degradation with dBET1, a proteolysis targeting chimera (PROTAC) that combines the highly selective BET inhibitor JQ1 and a ligand for cereblon E3 ubiquitin ligase, will reduce brain injury in ischemic stroke. Male aged mice (18-20 months old) were subjected to permanent occlusion of the middle cerebral artery and received either vehicle or dBET1 (10 mg/kg; i.p.) at various times after stroke. Neurobehavioral tests were performed before (baseline) and at 24 and 48 h after stroke induction. Infarct volume was quantified at 48 h. Data showed that BET degradation significantly reduced infarct volume in permanent focal cerebral ischemia in aged mice, and this was associated with reduced brain levels of pro-inflammatory mediators including [[TNF]]-α, [[CXCL1]], [[[[CXCL1]]0]], [[CCL2]], and matrix metalloproteinase-9. Treatment with dBET1 significantly reduced blood-brain barrier damage and infiltration of neutrophils into the ischemic brain. Importantly, treatment with the BET degrader dBET1 resulted in a significant improvement in stroke-induced neurological deficits. Collectively, these data indicate that BET proteins are a novel target for neuroprotection in ischemic stroke.
|mesh-terms=* Aging
* Animals
* Brain Injuries
* Brain Ischemia
* Disease Models, Animal
* Male
* Mice, Inbred C57BL
* Nerve Tissue Proteins
* Neuroprotective Agents
* Protein Transport
* Receptors, Cell Surface
* Stroke
* Transcription Factors
|keywords=* Aged mice
* BET proteins
* BRD4
* Ischemic stroke
* Neuroinflammation
* dBET1
|full-text-url=https://sci-hub.do/10.1016/j.neuint.2019.03.004
}}
{{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=Age-related pro-inflammatory and pro-angiogenic changes in human aqueous humor.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29487806
|abstract=To reveal age-related aqueous cytokine changes in human aqueous humor. Aqueous humor was collected from 12 young children (3-6.5 years old) and 71 healthy adults (22-106 years old) with cataract but without other systemic or ocular disorders. Levels of 22 cytokines, chemokines and vascular endothelial growth factor (VEGF) were measured and analyzed. The following proteins showed significant increase from childhood to adult: interferon-gamma (IFN-γ), interleukin (IL)-13, IL-6, IL-12(p70), IL-10, [[CCL2]], [[CCL3]], [[CCL4]], [[CXCL8]], [[CXCL9]], [[CXCL10]], IFN-α2 and VEGF (all [i]P[/i]<0.05). IFN-γ, IL-13, IL-12(p70), IL-10, [[CCL3]], [[CXCL9]] and VEGF also showed moderate strength age-related increase in the adult group ([i]r[/i]>0.5). The strength of correlation between aging and [[CCL4]] were fair ([i]r[/i]=0.398). The concentrations of IL-2, IL-4, IL-5, IL-1β and [[TNF]]-α were low in both groups. From childhood to adult, the immunological milieu of the anterior chamber become more pro-inflammatory and pro-angiogenic. Such changes may represent the parainflammation state of the human eye.

|keywords=* aging
* aqueous humor
* cytokines
* macrophage
* parainflammation
* vascular endothelial growth factor
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824071
}}
{{medline-entry
|title=Aged Chinese-origin rhesus macaques infected with SIV develop marked viremia in absence of clinical disease, inflammation or cognitive impairment.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29391069
|abstract=Damage to the central nervous system during HIV infection can lead to variable neurobehavioral dysfunction termed HIV-associated neurocognitive disorders (HAND). There is no clear consensus regarding the neuropathological or cellular basis of HAND. We sought to study the potential contribution of aging to the pathogenesis of HAND. Aged (range = 14.7-24.8 year) rhesus macaques of Chinese origin (RM-Ch) (n = 23) were trained to perform cognitive tasks. Macaques were then divided into four groups to assess the impact of SIVmac251 infection (n = 12) and combined antiretroviral therapy (CART) (5 infected; 5 mock-infected) on the execution of these tasks. Aged SIV-infected RM-Ch demonstrated significant plasma viremia and modest CSF viral loads but showed few clinical signs, no elevations of systemic temperature, and no changes in activity levels, platelet counts or weight. Concentrations of biomarkers of acute and chronic inflammation such as soluble [[CD14]], [[CXCL10]], IL-6 and [[TNF]]-α are known to be elevated following SIV infection of young adult macaques of several species, but concentrations of these biomarkers did not shift after SIV infection in aged RM-Ch and remained similar to mock-infected macaques. Neither acute nor chronic SIV infection or CART had a significant impact on accuracy, speed or percent completion in a sensorimotor test. Viremia in the absence of a chronic elevated inflammatory response seen in some aged RM-Ch is reminiscent of SIV infection in natural disease resistant hosts. The absence of cognitive impairment during SIV infection in aged RM-Ch might be in part attributed to diminishment of some facets of the immunological response. Additional study encompassing species and age differences is necessary to substantiate this hypothesis.
|mesh-terms=* Age Factors
* Aging
* Animals
* Antibodies, Viral
* Antiretroviral Therapy, Highly Active
* Asymptomatic Diseases
* Brain
* CD4-Positive T-Lymphocytes
* CD8-Positive T-Lymphocytes
* Cognitive Dysfunction
* Disease Models, Animal
* Female
* HIV Infections
* Humans
* Macaca mulatta
* RNA, Viral
* Simian Immunodeficiency Virus
* Viral Load
* Viremia
|keywords=* Aging
* Cognition
* HIV
* HIV-associated neurocognitive disorder
* Rhesus macaque
* Simian immunodeficiency virus
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796498
}}
{{medline-entry
|title=Immune senescence and biomarkers profile of Bambuí aged population-based cohort.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29247791
|abstract=During immunosenescence many proinflammatory markers such as cytokines and chemokines are increased. This process called by Franceschi and colleagues as inflammaging is associated with chronic inflammation and the ethiology and pathophysiolgy of many ageing diseases as Alzheimer's and atherosclerosis. The knowledge of immune profile during ageing may provide some interventions that would improve the immune function in elderly and quality of life for old people. However, the identification of a group of potential biomarkers to monitor the ageing process is very difficult. In addition, most of the evidence evaluating immune biomarkers profile is based on data from older Caucasian adults. To our knowledge, no previous Latin American old population-based cohort has evaluated immunological parameters along the ageing process. The present work evaluated [[CXCL8]], [[CXCL9]], [[CXCL10]], [[CCL2]], [[CCL5]], IL-1, IL-6, IL-12, [[TNF]] and IL-10 serum levels in 1494 older adults aged 60 to 95 from a population based ageing cohort in Brazil. Our data suggest that there is an increased positive predicted probability of participants to be a high producer of IL-6, [[CXCL8]] and [[CXCL9]]. Moreover, results did not differ between men and women, except for [[CXCL10]] that increased only in men. Results were not different in the adjusted model by many potential confounders, including African genomic ancestry. Together, these findings add novel insights about the immunologic aspects of ageing supported by a large population-based cohort study that provides evidences that corroborate with the inflammaging proposal and subsidize the establishment of biomarkers for monitoring the health status of aged population.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Biomarkers
* Brazil
* Chemokine CXCL10
* Chemokine CXCL9
* Cohort Studies
* Female
* Humans
* Immunosenescence
* Interleukin-6
* Interleukin-8
* Logistic Models
* Male
* Middle Aged
* Sex Factors
|keywords=* Ageing
* Biomarkers
* CXCL8
* CXCL9
* Gender
* IL-6
* Population-based cohort
|full-text-url=https://sci-hub.do/10.1016/j.exger.2017.12.006
}}
{{medline-entry
|title=Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29223680
|abstract=Chronic low-grade inflammation during aging (inflammaging) is associated with cognitive decline and neurodegeneration; however, the mechanisms underlying inflammaging are unclear. We studied a population (n = 361) of healthy young and old adults from the MyoAge cohort. Peripheral levels of C-X-C motif chemokine ligand 10 ([[CXCL10]]) was found to be higher in older adults, compared with young, and negatively associated with working memory performance. This coincided with an age-related reduction in blood DNA methylation at specific CpGs within the [[CXCL10]] gene promoter. In vitro analysis supported the role of DNA methylation in regulating [[CXCL10]] transcription. A polymorphism (rs56061981) that altered methylation at one of these CpG sites further associated with working memory performance in 2 independent aging cohorts. Studying prefrontal cortex samples, we found higher [[CXCL10]] protein levels in those with Alzheimer's disease, compared with aged controls. These findings support the association of peripheral inflammation, as demonstrated by [[CXCL10]], in aging and cognitive decline. We reveal age-related epigenetic and genetic factors which contribute to the dysregulation of [[CXCL10]].
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Alzheimer Disease
* Cerebral Cortex
* Chemokine CXCL10
* Cognition
* Cohort Studies
* DNA Methylation
* Epigenesis, Genetic
* Female
* HeLa Cells
* Humans
* Inflammation
* Male
* Memory
* Nerve Degeneration
* U937 Cells
* Young Adult
|keywords=* Alzheimer's disease
* Cognitive aging
* DNA methylation
* Epigenetics
* Inflammaging
* Neurodegeneration
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805841
}}
{{medline-entry
|title=Selected life-extending interventions reduce arterial [[CXCL10]] and macrophage colony-stimulating factor in aged mouse arteries.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28390264
|abstract=Cardiovascular disease (CVD) is the leading cause of death in the industrialized world. Aging is the most predictive risk factor for CVD and is associated with arterial inflammation which contributes to increased CVD risk. Although age-related arterial inflammation has been described in both humans and animals, only a limited number of inflammatory mediators, cytokines and chemokines have been identified. In this investigation we sought to determine whether lifespan extending interventions, including crowded litter early life nutrient deprivation (CL), traditional lifelong caloric restriction (CR) and lifelong Rapamycin treatment (Rap) would attenuate age-related arterial inflammation using multi analyte profiling. Aortas from Young (4-6months), Old (22months), Old CL, Old CR and Old Rap mice were homogenized and cytokine concentrations were assessed using Luminex Multi Analyte Profiling. Chemokines involved in immune cell recruitment, such as [[CCL2]], [[CXCL9]], [[CXCL10]], GMCSF and MCSF, were increased in Old vs. Young (p<0.05). The age-related increase of [[CXCL10]] was prevented by CR (p<0.05 vs. Old). MSCF concentrations were lower in aortas of Rap treated mice (p<0.05 vs. Old). Interleukins (IL), IL-1α, IL-1β and IL-10, were also greater in Old vs. Young mice (p<0.05). These data demonstrate selected lifespan extending interventions can prevent or limit age-related increases in selected aortic chemokines.
|mesh-terms=* Aging
* Animals
* Arteries
* Caloric Restriction
* Cardiovascular Diseases
* Chemokine CCL2
* Chemokine CCL4
* Chemokine CXCL10
* Chemokines
* Cytokines
* Early Medical Intervention
* Interleukin-10
* Interleukin-1beta
* Interleukins
* Macrophage Colony-Stimulating Factor
* Male
* Mice
* Sirolimus
|keywords=* Aorta
* Caloric restriction
* Chemokine
* Cytokine
* Interleukin
* Rapamycin
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544385
}}
{{medline-entry
|title=Interferon-gamma deficiency protects against aging-related goblet cell loss.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27623073
|abstract=Aging is a well-recognized risk factor for dry eye. Interferon-gamma (IFN-γ) has been implicated in conjunctival keratinization and goblet cell loss in dry eye. We investigated the role of IFN-γ in age-related dry eye by evaluating young (8 weeks) and aged (15 months; 15M) C57BL/6 (B6) and IFN-γKO mice. Age effects on the conjunctiva and cornea epithelium were assessed with PAS staining and corneal staining, respectively. Expression of T cell-related cytokines (IL-17A, IFN-γ), chemokines ([[CXCL10]] and [[CCL20]]), in the ocular surface epithelium was evaluated by real time PCR. A significant decrease in filled goblet cells was noted in 15M B6 mice and this was significantly lower than age and sex-matched IFN-γKO mice. Aged male B6 had significantly higher IFN-γ, and [[CXCL10]] mRNA in their conjunctiva than female B6 mice. Aged IFN-γKO females had significantly higher IL-17A mRNA in conjunctiva than IFN-γKO males and B6 mice. Corneal barrier dysfunction was observed in 15M female B6 and aged IFN-γKO mice of both sexes; however it was significantly higher in IFN-γKO compared to B6 mice. While there was a significant increase in IL 17A, and [[CCL20]] in corneas of aged female B6 and IFN-γKO mice compared to males, these changes were more evident in aged female IFN-γKO group.Partial resistance of IFN-γKO mice to aging-induced goblet cell loss indicates IFN-γ is involved in the age-related decline in conjunctival goblet cells. Increased corneal IL-17A expression paralleled corneal barrier disruption in aging female of both strains. IFN-γ appears to suppress IL-17A on the ocular surface.
|mesh-terms=* Aging
* Animals
* Cells, Cultured
* Chemokine CCL20
* Chemokine CXCL10
* Conjunctiva
* Cornea
* Disease Models, Animal
* Dry Eye Syndromes
* Female
* Goblet Cells
* Interferon-gamma
* Interleukin-17
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* T-Lymphocytes
|keywords=* Gerotarget
* IL-17
* aging
* dry eye
* goblet cells
* interferon-gamma
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323102
}}
{{medline-entry
|title=Behaviour and cognitive changes correlated with hippocampal neuroinflammaging and neuronal markers in female SAMP8, a model of accelerated senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27094468
|abstract=Senescence accelerated mice P8 (SAMP8) is a phenotypic model of age, characterized by deficits in memory and altered behaviour. Here, we determined the effect of age in SAMP8, and compared with the resistant strain, SAMR1, in behaviour and learning parameters linking these disturbances with oxidative stress environment. We found impairment in emotional behaviour with regard to fear and anxiety in young SAMP8 vs. age-mated SAMR1. Differences were attenuated with age. In contrast, learning capabilities are worse in SAMP8, both in young and aged animals, with regard to SAMR1. These waves in behaviour and cognition were correlated with an excess of oxidative stress (OS) in SAMP8 at younger ages that diminished with age. In this manner, we found changes in the hippocampal expression of [[ALDH2]], IL-6, [[HMOX1]], COX2, [[CXCL10]], iNOS, and MCP-1 with an altered amyloidogenic pathway by increasing the Amyloid beta precursor protein (APP) and [[BACE1]], and reduced [[ADAM10]] expression; in addition, astrogliosis and neuronal markers decreased. Moreover, Superoxide dismutase 1 (SOD1) and Nuclear factor-kappa beta (NF-kβ) expression and protein levels were higher in younger SAMP8 than in SAMR1. In conclusion, the accelerated senescence process present in SAMP8 can be linked with an initial deregulation in redox homeostasis, named neuroinflammaging, by inducing molecular changes that lead to neuroinflammation and the neurodegenerative process. These changes are reflected in the emotional and cognitive behaviour of SAMP8 that differs from that of SAMR1 and that highlighted the importance of earlier oxidative processes in the onset of neurodegeneration.
|mesh-terms=* Aging
* Animals
* Behavior, Animal
* Biomarkers
* Cognition
* Female
* Gene Expression
* Hippocampus
* Inflammation
* Male
* Memory
* Mice
* Models, Animal
* Oxidative Stress
|keywords=* Ageing
* Behaviour
* Cognition
* Inflammation
* Learning
* Neurodegeneration
* Oxidative stress
|full-text-url=https://sci-hub.do/10.1016/j.exger.2016.03.014
}}
{{medline-entry
|title=In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27081760
|abstract=Most infections occur in early life, prompting development of novel adjuvanted vaccines to protect newborns and infants. Several Toll-like receptor (TLR) agonists (TLRAs) are components of licensed vaccine formulations or are in development as candidate adjuvants. However, the type and magnitude of immune responses to TLRAs may vary with the TLR activated as well as age and geographic location. Most notably, in newborns, as compared to adults, the immune response to TLRAs is polarized with lower Th1 cytokine production and robust Th2 and anti-inflammatory cytokine production. The ontogeny of TLR-mediated cytokine responses in international cohorts has been reported, but no study has compared cytokine responses to TLRAs between U.S. neonates and infants at the age of 6months. Both are critical age groups for the currently pediatric vaccine schedule. In this study, we report quantitative differences in the production of a panel of 14 cytokines and chemokines after in vitro stimulation of newborn cord blood and infant and adult peripheral blood with agonists of [[TLR4]], including monophosphoryl lipid A (MPLA) and glucopyranosyl lipid Adjuvant aqueous formulation ([[GLA]]-AF), as well as agonists of TLR7/8 (R848) and [[TLR9]] (CpG). Both [[TLR4]] agonists, MPLA and [[GLA]]-AF, induced greater concentrations of Th1 cytokines [[CXCL10]], [[TNF]] and Interleukin (IL)-12p70 in infant and adult blood compared to newborn blood. All the tested TLRAs induced greater infant IFN-α2 production compared to newborn and adult blood. In contrast, CpG induced greater IFN-γ, IL-1β, IL-4, IL-12p40, IL-10 and [[CXCL8]] in newborn than in infant and adult blood. Overall, to the extent that these in vitro studies mirror responses in vivo, our study demonstrates distinct age-specific effects of TLRAs that may inform their development as candidate adjuvants for early life vaccines.
|mesh-terms=* Adjuvants, Immunologic
* Adult
* Aging
* Cytokines
* Female
* Humans
* Infant
* Infant, Newborn
* Male
* Oligodeoxyribonucleotides
* Th1 Cells
* Th2 Cells
* Toll-Like Receptors
|keywords=* Adjuvant
* Immune ontogeny
* Infant
* Neonate
* Newborn
* Toll-like receptor (TLR)
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906944
}}
{{medline-entry
|title=Thinning of the [[RPE]] and choroid associated with T lymphocyte recruitment in aged and light-challenged mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26392743
|abstract=Thinning of the [[RPE]] and the underlying vascular layer, the choroid, is observed with age in many human eye disorders. The reasons for this thinning are ill-defined. Here, we highlight the possible role of T lymphocyte recruitment in choroidoretinal thinning in aged and light-challenged mice. In age and light challenge models, we measured chemokine concentrations using enzyme-linked immunosorbent assay and used flow cytometry to characterize lymphocyte populations. We quantified thinning in eye immunosections and [[[[RPE]]65]] expression using quantitative PCR. Age and light challenge led to increased levels of the lymphotactic protein [[CXCL10]] alone (aging) or in conjunction with [[CXCL9]] (light challenge). Increased numbers of CD3  T lymphocytes, most of them CD8  cytotoxic T lymphocytes, were also observed in the choroid and retina of old mice and following light challenge. Influx of T lymphocytes was associated with [[RPE]] and choroidal thinning and diminished expression of [[[[RPE]]65]] mRNA, an essential enzyme of the visual cycle. The observations from this study suggest that cytotoxic CD8( ) T lymphocytes might participate in choroidal and [[RPE]] degeneration and that modulation of T lymphocyte recruitment might be a novel strategy to reduce choroidoretinal dysfunctions observed with age and following photo-oxidative stress.
|mesh-terms=* Aging
* Animals
* Cell Movement
* Chemokine CXCL10
* Chemokine CXCL9
* Choroid
* Gene Expression Regulation
* Humans
* Light
* Mice
* Mice, Inbred C57BL
* Oxidative Stress
* Photochemical Processes
* RNA, Messenger
* Retinal Pigment Epithelium
* T-Lymphocytes, Cytotoxic
* cis-trans-Isomerases

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558476
}}
{{medline-entry
|title=[[CCL2]], [[CXCL8]], [[CXCL9]] and [[CXCL10]] serum levels increase with age but are not altered by treatment with hydroxychloroquine in patients with osteoarthritis of the knees.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25955863
|abstract=Osteoarthritis (OA) is a major cause of morbidity and incapacity in the elderly. This study evaluates serum levels of the chemokines [[CCL2]], [[CXCL8]], [[CXCL9]], and [[CXCL10]] in 16 patients with primary OA of the knees, and investigates how treatment with hydroxychloroquine (HCQ) for 4 months affects these chemokine levels. Thirteen elderly patients received a placebo. Healthy control groups consisted of 10 elderly individuals (age > 60 years) with no clinical or radiological evidence of OA (CT-O), and 10 young adult individuals, (CT-Y group, age < 40 years). The CT-Y group presented lower levels of all chemokines studied, in comparison to the other groups. HCQ treatment did not alter the serum levels of [[CCL2]] (P = 0.80), [[CXCL8]] (P = 0.76), [[CXCL9]] (P = 0.95) and [[CXCL10]] (P = 0.74) in OA patients. Hydroxychloroquine treatment did not alter the serum levels of [[CCL2]], [[CXCL8]], [[CXCL9]] or [[CXCL10]] in patients with OA of the knees, although increased serum levels correlated with aging for all subjects, including controls.
|mesh-terms=* Age Factors
* Aged
* Aging
* Antirheumatic Agents
* Biomarkers
* Case-Control Studies
* Chemokine CCL2
* Chemokine CXCL10
* Chemokine CXCL9
* Female
* Humans
* Hydroxychloroquine
* Interleukin-8
* Male
* Middle Aged
* Osteoarthritis, Knee
* Time Factors
* Treatment Outcome
* Up-Regulation
|keywords=* aging
* arthritis
* chemokines
* hydroxychloroquine
* pain
|full-text-url=https://sci-hub.do/10.1111/1756-185X.12589
}}
{{medline-entry
|title=Cathelicidin related antimicrobial peptide, laminin, Toll-like receptors and chemokines levels in experimental hypersensitivity pneumonitis in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25834936
|abstract=Hypersensitivity pneumonitis ([[HP]]) is an interstitial lung disease caused by unresolved inflammation and tissue repair pathologies triggered by repeated organic dust exposure. The aim of the study was to investigate changes in levels of the cathelicidin related antimicrobial peptide (CRAMP), laminin (LAM-A1), selected Toll-like receptors (TLR) and chemokines in experimental [[HP]] in mice. Three and 18-month-old female C57BL/6J mice underwent inhalations of the saline extract of Pantoea agglomerans cells, Gram-negative bacterium common in organic dust and known for its pathogenic impact. The inhalations were repeated daily (28 days). ELISA was used for measuring in lung tissue homogenates concentration of CRAMP, LAM-A1, [[TLR2]], [[TLR4]], [[TLR8]], [[CXCL9]] (chemokine [C-X-C motif] ligand) and [[CXCL10]]. Levels of [[TLR2]], [[TLR4]] and [[CXCL9]] were significantly higher in both young and old mice lungs already after 7 days of inhalations, while significant increase of LAM-A1 and [[CXCL10]] was noted after 28 days, compared to untreated samples. [[TLR8]] level was significantly augmented only in young mice. Only CRAMP level significantly declined. Significantly higher [[TLR8]] and [[CXCL9]] concentration in untreated samples were noted in old animals compared to young ones. Significant alterations of the examined factors levels indicate their role in [[HP]] pathogenesis.
|mesh-terms=* Administration, Inhalation
* Aerosols
* Aging
* Alveolitis, Extrinsic Allergic
* Animals
* Antimicrobial Cationic Peptides
* Cathelicidins
* Cell Extracts
* Chemokine CXCL10
* Chemokine CXCL9
* Disease Models, Animal
* Female
* Laminin
* Mice
* Mice, Inbred C57BL
* Pantoea
* Protein Precursors
* Toll-Like Receptors
|keywords=* Antimicrobial peptide
* Hypersensitivity pneumonitis
* Mice model
* Modèle murin
* Pantoea agglomerans
* Peptides antimicrobiens
* Pneumopathie d’hypersensibilité
* Récepteurs de type Toll
* Toll-like receptors
|full-text-url=https://sci-hub.do/10.1016/j.patbio.2015.03.002
}}
{{medline-entry
|title=Viremic and Virologically Suppressed HIV Infection Increases Age-Related Changes to Monocyte Activation Equivalent to 12 and 4 Years of Aging, Respectively.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25647525
|abstract=Chronic inflammation and immune activation occur in both HIV infection and normal aging and are associated with inflammatory disease. However, the degree to which HIV influences age-related innate immune changes, and the biomarkers which best reflect them, remains unclear. We measured established innate immune aging biomarkers in 309 individuals including 88 virologically suppressed (VS) and 52 viremic (viral load ≤ and >50 copies per milliliter, respectively) HIV-positive individuals. Levels of soluble (ie, [[CXCL10]], soluble CD163, neopterin) and cellular (ie, proportions of inflammatory CD16 monocytes) biomarkers of monocyte activation were increased in HIV-positive individuals and were only partially ameliorated by viral suppression. Viremic and VS HIV-positive individuals show levels of age-related monocyte activation biomarkers that are similar to uninfected controls aged 12 and 4 years older, respectively. Viremic HIV infection was associated with an accelerated rate of change of some monocyte activation markers (eg, neopterin) with age, whereas in VS individuals, subsequent age-related changes occurred at a similar rate as in controls, albeit at a higher absolute level. We further identified [[CXCL10]] as a robust soluble biomarker of monocyte activation, highlighting the potential utility of this chemokine as a prognostic marker. These findings may partially explain the increased prevalence of inflammatory age-related diseases in HIV-positive individuals and potentially indicate the pathological mechanisms underlying these diseases, which persist despite viral suppression.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Antigens, CD
* Antigens, Differentiation, Myelomonocytic
* Biomarkers
* Chemokine CXCL10
* Cohort Studies
* Female
* GPI-Linked Proteins
* HIV Infections
* Humans
* Immunologic Factors
* Male
* Middle Aged
* Monocytes
* Neopterin
* Receptors, Cell Surface
* Receptors, IgG
* Young Adult

|full-text-url=https://sci-hub.do/10.1097/QAI.0000000000000559
}}
{{medline-entry
|title=Increased recruitment of bone marrow-derived cells into the brain associated with altered brain cytokine profile in senescence-accelerated mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25577138
|abstract=Bone marrow-derived cells enter the brain in a non-inflammatory condition through the attachments of choroid plexus and differentiate into ramified myeloid cells. Neurodegenerative conditions may be associated with altered immune-brain interaction. The senescence-accelerated mouse prone 10 (SAMP10) undergoes earlier onset neurodegeneration than C57BL/6 (B6) strain. We hypothesized that the dynamics of immune cells migrating from the bone marrow to the brain is perturbed in SAMP10 mice. We created 4 groups of radiation chimeras by intra-bone marrow-bone marrow transplantation using 2-month-old (2 mo) and 10 mo SAMP10 and B6 mice as recipients with GFP transgenic B6 mice as donors, and analyzed histologically 4 months later. In the [B6 → 10 mo SAMP10] chimeras, more ramified marrow-derived cells populated a larger number of discrete brain regions than the other chimeras, especially in the diencephalon. Multiplex cytokine assays of the diencephalon prepared from non-treated 3 mo and 12 mo SAMP10 and B6 mice revealed that 12 mo SAMP10 mice exhibited higher tissue concentrations of CXCL1, CCL11, G-CSF, [[CXCL10]] and IL-6 than the other groups. Immunohistologically, choroid plexus epithelium and ependyma produced CXCL1, while astrocytic processes in the attachments of choroid plexus expressed CCL11 and G-CSF. The median eminence produced [[CXCL10]], hypothalamic neurons G-CSF and tanycytes CCL11 and G-CSF. These brain cytokine profile changes in 12 mo SAMP10 mice were likely to contribute to acceleration of the dynamics of marrow-derived cells to the diencephalon. Further studies on the functions of ramified marrow-derived myeloid cells would enhance our understanding of the brain-bone marrow interaction.
|mesh-terms=* Aging
* Animals
* Astrocytes
* Bone Marrow Cells
* Brain
* Cell Movement
* Choroid Plexus
* Cytokines
* Ependyma
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
|keywords=* Astrocyte
* Bone marrow
* Choroid plexus
* Cytokine
* Ependyma
* Median eminence
* Tanycyte
|full-text-url=https://sci-hub.do/10.1007/s00429-014-0987-2
}}
{{medline-entry
|title=Dendritic cells from aged subjects contribute to chronic airway inflammation by activating bronchial epithelial cells under steady state.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24759206
|abstract=The mechanisms underlying the increased susceptibility of the elderly to respiratory infections are not well understood. The crosstalk between the dendritic cells (DCs) and epithelial cells is essential in maintaining tolerance as well as in generating immunity in the respiratory mucosa. DCs from aged subjects display an enhanced basal level of activation, which can affect the function of epithelial cells. Our results suggest that this is indeed the scenario as exposure of primary bronchial epithelial cells (PBECs) to supernatants from unstimulated DCs of aged subjects resulted in activation of PBECs. The expression of [[CCL20]], [[CCL26]], [[CXCL10]], mucin, and CD54 was significantly increased in the PBECs exposed to aged DC supernatants, but not to young DC supernatants. Furthermore, aged DC supernatants also enhanced the permeability of the PBEC barrier. We also found that DCs from aged subjects spontaneously secreted increased levels of pro-inflammatory mediators, interleukin-6, tumor necrosis factor ([[TNF]])-α, and metalloproteinase A disintegrin family of metalloproteinase 10, which can affect the functions of PBECs. Finally, we demonstrated that [[TNF]]-α, present in the supernatant of DCs from aged subjects, was the primary pro-inflammatory mediator that affected PBEC functions. Thus, age-associated alterations in DC-epithelial interactions contribute to chronic airway inflammation in the elderly, increasing their susceptibility to respiratory diseases. 
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Bronchi
* Cell Communication
* Cells, Cultured
* Chronic Disease
* Dendritic Cells
* Epithelial Cells
* Female
* Humans
* Inflammation Mediators
* Male
* Middle Aged
* Respiratory Mucosa
* Respiratory Tract Diseases

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205198
}}
{{medline-entry
|title=Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23365694
|abstract=Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8( ) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. HIV positive women exhibited elevated plasma levels of the innate immune activation markers [[CXCL10]] (p<0.001), soluble [[CD163]] (s[[CD163]], p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16( ) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers s[[CD163]] and the proportion of CD16( ) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. [[CXCL10]] increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers [[CXCL10]] and s[[CD163]] are independent of senescent changes in CD8( ) T lymphocytes. Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.
|mesh-terms=* Adult
* Age Factors
* Aging
* Antigens, CD
* Antigens, Differentiation, Myelomonocytic
* Biomarkers
* CD8-Positive T-Lymphocytes
* Case-Control Studies
* Chemokine CXCL10
* Cross-Sectional Studies
* Female
* GPI-Linked Proteins
* HIV
* HIV Infections
* Humans
* Immunity, Innate
* Immunophenotyping
* Lipopolysaccharide Receptors
* Middle Aged
* Monocytes
* Neopterin
* Receptors, Cell Surface
* Receptors, IgG

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554695
}}
{{medline-entry
|title=Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22708967
|abstract=Chronic inflammation in older individuals is thought to contribute to inflammatory, age-related diseases. Human monocytes are comprised of three subsets (classical, intermediate and nonclassical subsets), and despite being critical regulators of inflammation, the effect of age on the functionality of monocyte subsets remains to be fully defined. In a cross-sectional study involving 91 healthy male (aged 20-84 years, median 52.4) and 55 female (aged 20-82 years, median 48.3) individuals, we found age was associated with an increased proportion of intermediate and nonclassical monocytes (P = 0.002 and 0.04, respectively) and altered phenotype of specific monocyte subsets (e.g. increased expression of CD11b and decreased expression of [[CD38]], CD62L and CD115). Plasma levels of the innate immune activation markers [[CXCL10]], neopterin (P < 0.001 for both) and sCD163 (P = 0.003) were significantly increased with age. Whilst similar age-related changes were observed in both sexes, monocytes from women were phenotypically different to men [e.g. lower proportion of nonclassical monocytes (P = 0.002) and higher CD115 and CD62L but lower [[CD38]] expression] and women exhibited higher levels of [[CXCL10]] (P = 0.012) and sCD163 (P < 0.001) but lower sCD14 levels (P < 0.001). Monocytes from older individuals exhibit impaired phagocytosis (P < 0.05) but contain shortened telomeres (P < 0.001) and significantly higher intracellular levels of [[TNF]] both at baseline and following [[TLR4]] stimulation (P < 0.05 for both), suggesting a dysregulation of monocyte function in the aged. These data show that aging is associated with chronic innate immune activation and significant changes in monocyte function, which may have implications for the development of age-related diseases.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Chronic Disease
* Female
* Humans
* Immunity, Innate
* Inflammation
* Male
* Middle Aged
* Monocytes
* Phenotype
* Young Adult

|full-text-url=https://sci-hub.do/10.1111/j.1474-9726.2012.00851.x
}}
{{medline-entry
|title=HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22313961
|abstract=To compare the impact of HIV infection and healthy ageing on monocyte phenotype and function and determine whether age-related changes induced by HIV are reversed in antiretroviral treated individuals. A cross sectional study of monocyte ageing markers in viremic and virologically suppressed HIV-positive males aged 45 years or less and age-matched and elderly (≥65 years) HIV-uninfected individuals. Age-related changes to monocyte phenotype and function were measured in whole blood assays ex vivo on both CD14(  )CD16(-) (CD14( )) and CD14(variable)CD16( ) (CD16( )) subsets. Plasma markers relevant to innate immune activation were measured by ELISA. Monocytes from young viremic HIV-positive males resemble those from elderly controls, and show increased expression of CD11b (P < 0.0001 on CD14( ) and CD16( )subsets) and decreased expression of CD62L and CD115 (P = 0.04 and 0.001, respectively, on CD14( ) monocytes) when compared with young uninfected controls. These changes were also present in young virologically suppressed HIV-positive males. Innate immune activation markers neopterin, soluble [[CD163]] and [[CXCL10]] were elevated in both young viremic (P < 0.0001 for all) and virologically suppressed (P = 0.0005, 0.003 and 0.002, respectively) HIV-positive males with levels in suppressed individuals resembling those observed in elderly controls. Like the elderly, CD14( ) monocytes from young HIV-positive males exhibited impaired phagocytic function (P = 0.007) and telomere-shortening (P = 0.03) as compared with young uninfected controls. HIV infection induces changes to monocyte phenotype and function in young HIV-positive males that mimic those observed in elderly uninfected individuals, suggesting HIV may accelerate age-related changes to monocytes. Importantly, these defects persist in virologically suppressed HIV-positive individuals.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Anti-Retroviral Agents
* Biomarkers
* Cross-Sectional Studies
* Drug Therapy, Combination
* HIV Infections
* Humans
* Male
* Middle Aged
* Monocytes

|full-text-url=https://sci-hub.do/10.1097/QAD.0b013e328351f756
}}
{{medline-entry
|title=Defects in cytokine-mediated neuroprotective glial responses to excitotoxic hippocampal injury in senescence-accelerated mouse.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20804842
|abstract=Aging is a result of damage accumulation, and understanding of the mechanisms of aging requires exploration of the cellular and molecular systems functioning to control damage. Senescence-accelerated mouse prone 10 (SAMP10) has been established as an inbred strain exhibiting accelerated aging with an earlier onset of cognitive impairment due to neurodegeneration than the senescence-resistant control (SAMR1) strain. We hypothesized that tissue-protective responses of glial cells are impaired in SAMP10 mice. We injected kainic acid (KA) to induce hippocampal injury and studied how cytokines were upregulated on Day 3 using 3-month-old SAMP10 and SAMR1 mice. Following microarray-based screening for upregulated genes, we performed real-time RT-PCR and immunohistochemistry. Results indicated well-orchestrated cytokine-mediated glial interactions in the injured hippocampus of SAMR1 mice, in which microglia-derived interferon (IFN)-γ stimulated astrocytes via IFN-γ receptor and thereby induced expression of [[CXCL10]] and macrophage inflammatory protein (MIP)-1α, and activated microglia produced granulocyte-macrophage colony-stimulating factor (GM-CSF) and osteopontin (OPN). OPN was the most strongly upregulated cytokine. [[CD44]], an OPN receptor, was also strongly upregulated in the neuropil, especially on neurons and astrocytes. KA-induced hippocampal upregulation of these cytokines was strikingly reduced in SAMP10 mice compared to SAMR1 mice. On Day 30 after KA injection, SAMP10 but not SAMR1 mice exhibited hippocampal layer atrophy. Since the OPN-[[CD44]] system is essential for neuroprotection and remodeling, these findings highlight the defects of SAMP10 mice in cytokine-mediated neuroprotective glia-neuron interactions, which may be associated with the mechanism underlying the vulnerability of SAMP10 mice to age-related neurodegeneration.
|mesh-terms=* Aging
* Animals
* Astrocytes
* Cell Size
* Cytokines
* Gene Expression
* Hippocampus
* Hyaluronan Receptors
* Immunohistochemistry
* Kainic Acid
* Mice
* Mice, Neurologic Mutants
* Microglia
* Neuroglia
* Neurons
* Neurotoxins
* Oligonucleotide Array Sequence Analysis
* Reverse Transcriptase Polymerase Chain Reaction
* Signal Transduction
* Up-Regulation

|full-text-url=https://sci-hub.do/10.1016/j.bbi.2010.08.006
}}
{{medline-entry
|title=Increase of CXC chemokine [[CXCL10]] and CC chemokine [[CCL2]] serum levels in normal ageing.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16697212
|abstract=No study has evaluated contemporaneously serum CXC and CC chemokines changes in normal ageing. Serum levels of [[CXCL10]] (s[[CXCL10]]) (CXC) and [[CCL2]] (s[[CCL2]]) (CC) prototype chemokines have been measured in 164 healthy subjects, from 10 to 79 years of age (82 males/82 females). By simple regression analysis, s[[CXCL10]] and s[[CCL2]] were significantly related with increasing age (r=0.32, p<0.001; r=0.31, p<0.0001, respectively), and with each other (r=0.30, p=0.0004). In a multiple linear regression model, only age and s[[CCL2]] were significantly related to s[[CXCL10]] levels (p<0.001); age and s[[CXCL10]] were significantly related to s[[CCL2]] levels (p<0.001). Subjects with high s[[CXCL10]] levels (>150 pg/ml) were not significantly associated with those with high s[[CCL2]] levels (>559 pg/ml). This study, performed in healthy subjects on an age gradient, demonstrates an increase of s[[CXCL10]] and s[[CCL2]] with advancing age; the differential increase of s[[CXCL10]] or s[[CCL2]] may reflect a general shift towards Th1 or Th2 cytokines pattern, respectively.
|mesh-terms=* Adolescent
* Adult
* Age Factors
* Aged
* Aging
* Chemokine CCL2
* Chemokine CXCL10
* Chemokines, CXC
* Child
* Cytokines
* Female
* Humans
* Male
* Middle Aged
* Regression Analysis
* Thyroid Gland
* Ultrasonography

|full-text-url=https://sci-hub.do/10.1016/j.cyto.2006.03.012
}}
{{medline-entry
|title=Age-dependent changes in CXC chemokine ligand 10 serum levels in euthyroid subjects.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16181055
|abstract=Circulating levels of cytokines are deeply influenced by aging, and few data about serum chemokines are available. The aim of this study was to evaluate the influence of aging on circulating [[CXCL10]]. One hundred forty healthy subjects (70 males and 70 females), 10-79 years of age, underwent fasting plasma glucose, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, and [[CXCL8]] serum assay. Thyroid hormone testing for thyroid-stimulating hormone (TSH), antithyroglobulin (AbTg), and antithyroperoxidase (AbTPO) autoantibodies and thyroid ultrasonography were performed in all subjects to exclude the presence of clinical or subclinical thyroid disease. Serum [[CXCL10]] levels were assayed in all subjects and found to be increased in 14 of 70 females (20%) and in 4 of 70 males (5.7%) (p = 0.01). In a multiple linear regression model including age, body mass index (BMI), systolic and diastolic blood pressure, glycemia, total cholesterol, HDL, LDL, triglycerides, TSH, AbTPO, AbTg, and [[CXCL8]], only age was significantly related to [[CXCL10]] [C.R. 1.30 (0.28-2.33), p = 0.001]. No relationship was present between [[CXCL8]] serum levels and age, suggesting a specificity of [[CXCL10]] elevation as a function of age. Results of this study, performed in healthy subjects on an age gradient, demonstrate an increase in serum [[CXCL10]] with advancing age overall in females, supporting the hypothesis of enhanced Th1 immune responses in aging.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aging
* Chemokine CXCL10
* Chemokines, CXC
* Child
* Female
* Humans
* Male
* Middle Aged
* Thyroid Diseases

|full-text-url=https://sci-hub.do/10.1089/jir.2005.25.547
}}
{{medline-entry
|title=Age-associated changes in functional response to [[CXCR3]] and [[CXCR5]] chemokine receptors in human osteoblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/14618028
|abstract=The expression and functional activity of CXC chemokine receptors were evaluated in human osteoblasts (OB) obtained post-trauma from old donors compared to very young donors. It was found that [[CXCR1]] and [[CXCR4]] were only expressed by old but not young donors' cells. In contrast, [[CXCR3]] and [[CXCR5]] were expressed by both young and old donors. We functionally evaluated [[CXCR3]]/[[CXCL10]] and [[CXCR5]]/[[CXCL13]] receptor/ligand pairs by analysing cell proliferation and the release of N-acetyl-beta-D-glucosaminidase (NAG), an enzyme that degrades glycosaminoglycans and hyaluronic acid. [[CXCL10]] and [[CXCL13]] induced a dose-dependent increase of cell proliferation in OB from young donors while cell proliferation of OB in old donors was not affected. By contrast, [[CXCL10]] and [[CXCL13]] induced a significantly higher NAG release in OB from old donors compared to young ones. These data demonstrate a significant age-dependent difference in the response of OB to [[CXCL10]] and [[CXCL13]] stimulation. These chemokines induce an inverse response of OB from old and young donors, which suggests a role of ageing in the modulation of cellular response of bone cells.
|mesh-terms=* Aged
* Aging
* Alkaline Phosphatase
* Cell Division
* Cells, Cultured
* Chemokine CXCL10
* Chemokine CXCL13
* Chemokines, CXC
* Child, Preschool
* Humans
* Infant
* Osteoblasts
* Receptors, CXCR3
* Receptors, CXCR5
* Receptors, Chemokine
* Receptors, Cytokine

|full-text-url=https://sci-hub.do/10.1023/a:1026203502385
}}