Aging Cell最新文献

{"title":"Cardiomyocyte Pdk4 response is associated with metabolic maladaptation in aging","authors":"Mohammad Kasim Fatmi,&nbsp;Di Ren,&nbsp;Julia Fedorova,&nbsp;Linda Ines Zoungrana,&nbsp;Hao Wang,&nbsp;Kayla Davitt,&nbsp;Zehui Li,&nbsp;Migdalia Iglesias,&nbsp;Edward J. Lesnefsky,&nbsp;Meredith Krause-Hauch,&nbsp;Ji Li","doi":"10.1111/acel.13800","DOIUrl":"https://doi.org/10.1111/acel.13800","url":null,"abstract":"<p>Ischemic heart disease (IHD) is the leading cause of death, with age range being the primary factor for development. The mechanisms by which aging increases vulnerability to ischemic insult are not well understood. We aim to use single-cell RNA sequencing to discover transcriptional differences in various cell types between aged and young mice, which may contribute to aged-related vulnerability to ischemic insult. Utilizing 10× Genomics Single-Cell RNA sequencing, we were able to complete bioinformatic analysis to identity novel differential gene expression. During the analysis of our collected samples, we detected Pyruvate Dehydrogenase Kinase 4 (Pdk4) expression to be remarkably differentially expressed. Particularly in cardiomyocyte cell populations, Pdk4 was found to be significantly upregulated in the young mouse population compared to the aged mice under ischemic/reperfusion conditions. Pdk4 is responsible for inhibiting the enzyme pyruvate dehydrogenase, resulting in the regulation of glucose metabolism. Due to decreased Pdk4 expression in aged cardiomyocytes, there may be an increased reliance on glucose oxidization for energy. Through biochemical metabolomics analysis, it was observed that there is a greater abundance of pyruvate in young hearts in contrast to their aged counterparts, indicating less glycolytic activity. We believe that Pdk4 response provides valuable insight towards mechanisms that allow for the young heart to handle ischemic insult stress more effectively than the aged heart.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13800","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5683141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of pulmonary epithelial arginase-II in activation of fibroblasts and lung inflammaging","authors":"Cui Zhu,&nbsp;Duilio M. Potenza,&nbsp;Yang Yang,&nbsp;Guillaume Ajalbert,&nbsp;Kirsten D. Mertz,&nbsp;Stephan von Gunten,&nbsp;Xiu-Fen Ming,&nbsp;Zhihong Yang","doi":"10.1111/acel.13790","DOIUrl":"https://doi.org/10.1111/acel.13790","url":null,"abstract":"<p>Elevated arginases including type-I (Arg-I) and type-II isoenzyme (Arg-II) are reported to play a role in aging, age-associated organ inflammaging, and fibrosis. A role of arginase in pulmonary aging and underlying mechanisms are not explored. Our present study shows increased Arg-II levels in aging lung of female mice, which is detected in bronchial ciliated epithelium, club cells, alveolar type 2 (AT2) pneumocytes, and fibroblasts (but not vascular endothelial and smooth muscle cells). Similar cellular localization of Arg-II is also observed in human lung biopsies. The age-associated increase in lung fibrosis and inflammatory cytokines, including IL-1β and TGF-β1 that are highly expressed in bronchial epithelium, AT2 cells, and fibroblasts, are ameliorated in <i>arg-ii</i> deficient (<i>arg-ii</i>^{<i>−/−</i>}) mice. The effects of <i>arg-ii</i>^{<i>−</i>/−} on lung inflammaging are weaker in male as compared to female animals. Conditioned medium (CM) from human Arg-II-positive bronchial and alveolar epithelial cells, but not that from <i>arg-ii</i>^{<i>−/−</i>} cells, activates fibroblasts to produce various cytokines including TGF-β1 and collagen, which is abolished by IL-1β receptor antagonist or TGF-β type I receptor blocker. Conversely, TGF-β1 or IL-1β also increases Arg-II expression. In the mouse models, we confirmed the age-associated increase in IL-1β and TGF-β1 in epithelial cells and activation of fibroblasts, which is inhibited in <i>arg-ii</i>^{<i>−</i>/−} mice. Taken together, our study demonstrates a critical role of epithelial Arg-II in activation of pulmonary fibroblasts via paracrine release of IL-1β and TGF-β1, contributing to pulmonary inflammaging and fibrosis. The results provide a novel mechanistic insight in the role of Arg-II in pulmonary aging.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5651727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Featured Cover","authors":"Anna Konstorum,&nbsp;Subhasis Mohanty,&nbsp;Yujiao Zhao,&nbsp;Anthony Melillo,&nbsp;Brent Vander Wyk,&nbsp;Allison Nelson,&nbsp;Sui Tsang,&nbsp;Tamara P. Blevins,&nbsp;Robert?B. Belshe,&nbsp;Daniel G. Chawla,&nbsp;Matthew T. Rondina,&nbsp;Thomas M. Gill,&nbsp;Ruth R. Montgomery,&nbsp;Heather G. Allore,&nbsp;Steven H. Kleinstein,&nbsp;Albert C. Shaw","doi":"10.1111/acel.13801","DOIUrl":"https://doi.org/10.1111/acel.13801","url":null,"abstract":"<p>Cover legend: The cover image is based on the Research Article <i>Platelet response to infl uenza vaccination refl ects effects of aging</i> by Anna Konstorum et al., https://doi.org/10.1111/acel.13749. Image Credit: Hannah Wang\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6236138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA repair in cardiomyocytes is critical for maintaining cardiac function in mice","authors":"Martine de Boer,&nbsp;Maaike te Lintel?Hekkert,&nbsp;Jiang Chang,&nbsp;Bibi S. van Thiel,&nbsp;Leonie Martens,&nbsp;Maxime M. Bos,&nbsp;Marion G. J. de Kleijnen,&nbsp;Yanto Ridwan,&nbsp;Yanti Octavia,&nbsp;Elza D. van Deel,&nbsp;Lau A. Blonden,&nbsp;Renata M. C. Brandt,&nbsp;Sander Barnhoorn,&nbsp;Paula K. Bautista-Ni?o,&nbsp;Ilona Krabbendam-Peters,&nbsp;Rianne Wolswinkel,&nbsp;Banafsheh Arshi,&nbsp;Mohsen Ghanbari,&nbsp;Christian Kupatt,&nbsp;Leon J. de Windt,&nbsp;A. H. Jan Danser,&nbsp;Ingrid van der Pluijm,&nbsp;Carol?Ann Remme,&nbsp;Monika Stoll,&nbsp;Joris Pothof,&nbsp;Anton J. M. Roks,&nbsp;Maryam Kavousi,&nbsp;Jeroen Essers,&nbsp;Jolanda van der Velden,&nbsp;Jan H. J. Hoeijmakers,&nbsp;Dirk J. Duncker","doi":"10.1111/acel.13768","DOIUrl":"https://doi.org/10.1111/acel.13768","url":null,"abstract":"<p>Heart failure has reached epidemic proportions in a progressively ageing population. The molecular mechanisms underlying heart failure remain elusive, but evidence indicates that DNA damage is enhanced in failing hearts. Here, we tested the hypothesis that endogenous DNA repair in cardiomyocytes is critical for maintaining normal cardiac function, so that perturbed repair of spontaneous DNA damage drives early onset of heart failure. To increase the burden of spontaneous DNA damage, we knocked out the DNA repair endonucleases xeroderma pigmentosum complementation group G (XPG) and excision repair cross-complementation group 1 (ERCC1), either systemically or cardiomyocyte-restricted, and studied the effects on cardiac function and structure. Loss of DNA repair permitted normal heart development but subsequently caused progressive deterioration of cardiac function, resulting in overt congestive heart failure and premature death within 6 months. Cardiac biopsies revealed increased oxidative stress associated with increased fibrosis and apoptosis. Moreover, gene set enrichment analysis showed enrichment of pathways associated with impaired DNA repair and apoptosis, and identified TP53 as one of the top active upstream transcription regulators. In support of the observed cardiac phenotype in mutant mice, several genetic variants in the <i>ERCC1</i> and <i>XPG</i> gene in human GWAS data were found to be associated with cardiac remodelling and dysfunction. In conclusion, unrepaired spontaneous DNA damage in differentiated cardiomyocytes drives early onset of cardiac failure. These observations implicate DNA damage as a potential novel therapeutic target and highlight systemic and cardiomyocyte-restricted DNA repair-deficient mouse mutants as <i>bona fide</i> models of heart failure.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13768","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6150024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bifidobacterium longum supplementation improves age-related delays in fracture repair","authors":"Joseph L. Roberts,&nbsp;Mateo Golloshi,&nbsp;Derek B. Harding,&nbsp;Madison Conduah,&nbsp;Guanglu Liu,&nbsp;Hicham Drissi","doi":"10.1111/acel.13786","DOIUrl":"https://doi.org/10.1111/acel.13786","url":null,"abstract":"<p>Age-related delays in bone repair remains an important clinical issue that can prolong pain and suffering. It is now well established that inflammation increases with aging and that this exacerbated inflammatory response can influence skeletal regeneration. Recently, simple dietary supplementation with beneficial probiotic bacteria has been shown to influence fracture repair in young mice. However, the contribution of the gut microbiota to age-related impairments in fracture healing remains unknown. Here, we sought to determine whether supplementation with a single beneficial probiotic species, <i>Bifidobacterium longum</i> (<i>B. longum</i>), would promote fracture repair in aged (18-month-old) female mice. We found that <i>B. longum</i> supplementation accelerated bony callus formation which improved mechanical properties of the fractured limb. We attribute these pro-regenerative effects of <i>B. longum</i> to preservation of intestinal barrier, dampened systemic inflammation, and maintenance of the microbiota community structure. Moreover, <i>B. longum</i> attenuated many of the fracture-induced systemic pathologies. Our study provides evidence that targeting the gut microbiota using simple dietary approaches can improve fracture healing outcomes and minimize systemic pathologies in the context of aging.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5847474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice","authors":"Andrés Pastor-Fernández,&nbsp;Antonio R. Bertos,&nbsp;Arantzazu Sierra-Ramírez,&nbsp;Javier del Moral-Salmoral,&nbsp;Javier Merino,&nbsp;Ana I. de ávila,&nbsp;Cristina Olagüe,&nbsp;Ricardo Villares,&nbsp;Gloria González-Aseguinolaza,&nbsp;María ángeles Rodríguez,&nbsp;Manuel Fresno,&nbsp;Nuria Gironés,&nbsp;Matilde Bustos,&nbsp;Cristian Smerdou,&nbsp;Pablo Jose Fernandez-Marcos,&nbsp;Cayetano von Kobbe","doi":"10.1111/acel.13771","DOIUrl":"https://doi.org/10.1111/acel.13771","url":null,"abstract":"<p>The enormous societal impact of the ongoing COVID-19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro-inflammatory immune response against SARS-CoV-2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID-19 in some cases. Using the established COVID-19 murine model K18-hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS-CoV-2-related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS-CoV-2 may be related to the post-COVID-19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID-19, and make D/Q a new and promising therapeutic tool.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5862819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic alcohol metabolism results in DNA repair infidelity and cell cycle-induced senescence in neurons","authors":"Jacquelyne Ka-Li Sun,&nbsp;Deng Wu,&nbsp;Genper Chi-Ngai Wong,&nbsp;Tsun-Ming Lau,&nbsp;Meigui Yang,&nbsp;Ronald P. Hart,&nbsp;Kin-Ming Kwan,&nbsp;Ho Yin Edwin Chan,&nbsp;Hei-Man Chow","doi":"10.1111/acel.13772","DOIUrl":"https://doi.org/10.1111/acel.13772","url":null,"abstract":"<p>Chronic binge-like drinking is a risk factor for age-related dementia, however, the lasting and irreversible effect of alcohol on the brain remains elusive. Transcriptomic changes in brain cortices revealed pro-ageing hallmarks upon chronic ethanol exposure and these changes predominantly occur in neurons. The changes are attributed to a prioritized ethyl alcohol oxidation in these cells via the NADPH-dependent cytochrome pathway. This hijacks the folate metabolism of the 1-carbon network which supports the pathway choice of DNA repair via the non-cell cycle-dependent mismatch repair networks. The lost-in-function of such results in the de-inactivation of the less preferred cell cycle-dependent homologous recombination (HR) repair, forcing these post-mitotic cells to re-engage in a cell cycle-like process. However, mature neurons are post-mitotic. Therefore, instead of successfully completing a full round of cell cycle which is necessary for the completion of HR-mediated repair; these cells are arrested at checkpoints. The resulting persistence of repair intermediates induces and promotes the nuclear accumulation of p21 and cyclin B—a trigger for permanent cell cycle exits and irreversible senescence response. Supplementation of bioactive 5-methyl tetrahydrofolate simultaneously at times with ethyl alcohol exposure supports the fidelity of the 1-carbon network and hence the activity of the mismatch repair. This prevents aberrant and irreversible cell cycle re-entry and senescence events of neurons. Together, our findings offer a direct connection between binge-drinking behaviour and its irreversible impact on the brain, which makes it a potential risk factor for dementia.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13772","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5763816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-associated adipose tissue inflammation promotes monocyte chemotaxis and enhances atherosclerosis","authors":"Jianrui Song,&nbsp;Diana Farris,&nbsp;Paola Ariza,&nbsp;Smriti Moorjani,&nbsp;Mita Varghese,&nbsp;Muriel Blin,&nbsp;Judy Chen,&nbsp;Daniel Tyrrell,&nbsp;Min Zhang,&nbsp;Kanakadurga Singer,&nbsp;Morgan Salmon,&nbsp;Daniel R. Goldstein","doi":"10.1111/acel.13783","DOIUrl":"https://doi.org/10.1111/acel.13783","url":null,"abstract":"<p>Although aging enhances atherosclerosis, we do not know if this occurs via alterations in circulating immune cells, lipid metabolism, vasculature, or adipose tissue. Here, we examined whether aging exerts a direct pro-atherogenic effect on adipose tissue in mice. After demonstrating that aging augmented the inflammatory profile of visceral but not subcutaneous adipose tissue, we transplanted visceral fat from young or aged mice onto the right carotid artery of <i>Ldlr</i>^−/− recipients. Aged fat transplants not only increased atherosclerotic plaque size with increased macrophage numbers in the adjacent carotid artery, but also in distal vascular territories, indicating that aging of the adipose tissue enhances atherosclerosis via secreted factors. By depleting macrophages from the visceral fat, we identified that adipose tissue macrophages are major contributors of the secreted factors. To identify these inflammatory factors, we found that aged fat transplants secreted increased levels of the inflammatory mediators TNFα, CXCL2, and CCL2, which synergized to promote monocyte chemotaxis. Importantly, the combined blockade of these inflammatory mediators impeded the ability of aged fat transplants to enhance atherosclerosis. In conclusion, our study reveals that aging enhances atherosclerosis via increased inflammation of visceral fat. Our study suggests that future therapies targeting the visceral fat may reduce atherosclerosis disease burden in the expanding older population.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13783","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5787743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The variant senescence-associated secretory phenotype induced by centrosome amplification constitutes a pathway that activates hypoxia-inducible factor-1α","authors":"Selwin K. Wu,&nbsp;Juliana Ariffin,&nbsp;Shu Chian Tay,&nbsp;Remigio Picone","doi":"10.1111/acel.13766","DOIUrl":"https://doi.org/10.1111/acel.13766","url":null,"abstract":"<p>The senescence-associated secretory phenotype (SASP) can promote paracrine invasion while suppressing tumour growth, thus generating complex phenotypic outcomes. Likewise, centrosome amplification can induce proliferation arrest yet also facilitate tumour invasion. However, the eventual fate of cells with centrosome amplification remains elusive. Here, we report that centrosome amplification induces a variant of SASP, which constitutes a pathway activating paracrine invasion. The centrosome amplification-induced SASP is non-canonical as it lacks the archetypal detectable DNA damage and prominent NF-κB activation, but involves Rac activation and production of reactive oxygen species. Consequently, it induces hypoxia-inducible factor 1α and associated genes, including pro-migratory factors such as ANGPTL4. Of note, cellular senescence can either induce tumourigenesis through paracrine signalling or conversely suppress tumourigenesis through p53 induction. By analogy, centrosome amplification-induced SASP may therefore be one reason why extra centrosomes promote malignancy in some experimental models but are neutral in others.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13766","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5718793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet response to influenza vaccination reflects effects of aging","authors":"Anna Konstorum,&nbsp;Subhasis Mohanty,&nbsp;Yujiao Zhao,&nbsp;Anthony Melillo,&nbsp;Brent Vander Wyk,&nbsp;Allison Nelson,&nbsp;Sui Tsang,&nbsp;Tamara P. Blevins,&nbsp;Robert?B. Belshe,&nbsp;Daniel G. Chawla,&nbsp;Matthew T. Rondina,&nbsp;Thomas M. Gill,&nbsp;Ruth R. Montgomery,&nbsp;Heather G. Allore,&nbsp;Steven H. Kleinstein,&nbsp;Albert C. Shaw","doi":"10.1111/acel.13749","DOIUrl":"https://doi.org/10.1111/acel.13749","url":null,"abstract":"<p>Platelets are uniquely positioned as mediators of not only hemostasis but also innate immunity. However, how age and geriatric conditions such as frailty influence platelet function during an immune response remains unclear. We assessed the platelet transcriptome at baseline and following influenza vaccination in Younger (age 21–35) and Older (age ≥65) adults (including community-dwelling individuals who were largely non-frail and skilled nursing facility (SNF)-resident adults who nearly all met criteria for frailty). Prior to vaccination, we observed an age-associated increase in the expression of platelet activation and mitochondrial RNAs and decrease in RNAs encoding proteins mediating translation. Age-associated differences were also identified in post-vaccination response trajectories over 28 days. Using tensor decomposition analysis, we found increasing RNA expression of genes in platelet activation pathways in young participants, but decreasing levels in (SNF)-resident adults. Translation RNA trajectories were inversely correlated with these activation pathways. Enhanced platelet activation was found in community-dwelling older adults at the protein level, compared to young individuals both prior to and post-vaccination; whereas SNF residents showed decreased platelet activation compared to community-dwelling older adults that could reflect the influence of decreased translation RNA expression. Our results reveal alterations in the platelet transcriptome and activation responses that may contribute to age-associated chronic inflammation and the increased incidence of thrombotic and pro-inflammatory diseases in older adults.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5928546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}