Aging Cell最新文献

{"title":"Circadian Gene BMAL1 Regulation of Cellular Senescence in Thyroid Aging.","authors":"Dandan Zong, Baihui Sun, Qiting Ye, Hongxin Cao, Haixia Guan","doi":"10.1111/acel.70119","DOIUrl":"https://doi.org/10.1111/acel.70119","url":null,"abstract":"<p><p>As global aging accelerates, the incidence of thyroid diseases, particularly hypothyroidism, is rising in the elderly. The thyroid-stimulating hormone (TSH) levels increase in healthy elderly populations. However, whether the thyroid undergoes cellular senescence and how this relates to thyroid hormone (TH) synthesis remain unclear. To investigate the molecular and functional characteristics of thyroid aging, we performed scRNA-seq on human thyroids from young, middle-aged, and old groups, identifying thousands of aging-related differentially expressed genes and revealing the early onset of aging in the middle-aged group. As aging progresses, the expression levels of genes related to TH synthesis increase, suggesting that epithelial cells (EPI) adjust their gene expression in response to elevated TSH levels. Additionally, the senescence-associated secretory phenotype (SASP) in EPI cells is progressively enhanced with aging. We identified a subgroup of epithelial cells (CDKN1A_EPI) characterized by reduced functionality and significantly elevated levels of cellular senescence. We found that the core circadian rhythm gene BMAL1 (ARNTL) is downregulated during aging. We further validated this finding using the thyroid-specific Bmal1 knockout mouse model, showing that the downregulation of Bmal1 inhibits the expression of Nfkbia (NF-κB inhibitor alpha), thereby accelerating cellular senescence and impairing hormone synthesis. Finally, through cell line experiments and transcriptome sequencing, we confirmed that BMAL1 knockout leads to decreased NFKBIA expression, promoting thyroid cellular senescence. Our study demonstrates that circadian rhythm disruption accelerates cellular senescence in the thyroid and exacerbates the decline of thyroid function, providing a novel theoretical foundation for understanding thyroid aging mechanisms and maintaining thyroid function stability.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70119"},"PeriodicalIF":8.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin and Dietary Restriction Counteract Aging via Reducing m6A-Dependent Stabilization of Methionine Synthase mRNA in Brachionus asplanchnoidis (Rotifera).","authors":"Yu Zhang, Xiaojie Liu, Hairong Lian, Yanchao Chai, Yang Zhou, Dongqi Kan, Jilong Ren, Cui Han, Jiaxin Yang","doi":"10.1111/acel.70113","DOIUrl":"https://doi.org/10.1111/acel.70113","url":null,"abstract":"<p><p>Metformin, a medication primarily used to treat diabetes, has gained attentions for its potential antiaging properties. Although the metabolic and cellular pathways behind its longevity effects have been widely studied, few studies have explored the epigenetic regulatory effects of metformin, which are a crucial factor in aging processes. In this study, we examined the antiaging effects of metformin using the Brachionus rotifer as a model, focusing on the regulation of mRNA N6-methyladenosine (m6A), a key RNA modification involved in mRNA stability, translation, and splicing. We found metformin significantly extended the rotifers' lifespan, mimicking the effects of dietary restriction (DR), a well-established antiaging intervention. Both metformin and DR modulate m6A dynamics, with a notable reduction in the m6A modification of MTR (5-methyltetrahydrofolate-homocysteine methyltransferase). This reduction led to decreased MTR expression and lowered levels of S-adenosylmethionine (SAM), a critical metabolite in the one-carbon cycle. We propose that the downregulation of MTR through m6A modification limits methionine synthesis and imposes methionine restriction, a key factor in promoting longevity. Our findings reveal a novel epitranscriptional regulatory model by which metformin and DR modulate m6A to extend lifespan, highlighting MTR as a central regulator of aging and suggesting potential therapeutic strategies for healthy aging through m6A and methionine metabolism.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70113"},"PeriodicalIF":8.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Omics Analysis Reveals Biomarkers That Contribute to Biological Age Rejuvenation in Response to Single-Blinded Randomized Placebo-Controlled Therapeutic Plasma Exchange.","authors":"Matias Fuentealba, Dobri Kiprov, Kevin Schneider, Wei-Chieh Mu, Prasanna Ashok Kumaar, Herbert Kasler, Jordan B Burton, Mark Watson, Heather Halaweh, Christina D King, Zehra Stara Yüksel, Chelo Roska-Pamaong, Birgit Schilling, Eric Verdin, David Furman","doi":"10.1111/acel.70103","DOIUrl":"https://doi.org/10.1111/acel.70103","url":null,"abstract":"<p><p>We conducted a randomized, placebo-controlled trial to assess the safety and biological age (BA) effects of various therapeutic plasma exchange (TPE) regimens in healthy adults over 50. Participants received bi-weekly TPE with or without intravenous immunoglobulin (IVIG), monthly TPE, or placebo. Randomization was based on entry date, and treatments were blinded to maintain objectivity. Primary objectives were to assess long-term TPE safety and changes in biological clocks. Secondary goals included identifying optimal regimens. Exploratory analyses profiled baseline clinical features and longitudinal changes across the epigenome, proteome, metabolome, glycome, immune cytokines, iAge, and immune cell composition. We demonstrate in 42 individuals randomized to various treatment arms or placebo that long-term TPE was found to be safe, with only two adverse events requiring discontinuation and one related to IVIG. TPE significantly improved biological age markers, with 15 epigenetic clocks showing rejuvenation compared to placebo (FDR < 0.05). Biweekly TPE combined with intravenous immunoglobulin (TPE-IVIG) proved most effective, inducing coordinated cellular and molecular responses, reversing age-related immune decline, and modulating proteins linked to chronic inflammation. Integrative analysis identified baseline biomarkers predictive of positive outcomes, suggesting TPE-IVIG is particularly beneficial for individuals with poorer initial health status. This is the first multi-omics study to examine various TPE modalities to slow epigenetic biologic clocks, which demonstrate biological age rejuvenation and the molecular features associated with this rejuvenation. Trial Registration: Registered trial NCT06534450 on clinicaltrials.gov under the purview of the Diagnostic Investigational Review Board.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70103"},"PeriodicalIF":8.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ElixirSeeker: A Machine Learning Framework Utilizing Fusion Molecular Fingerprints for the Discovery of Lifespan-Extending Compounds.","authors":"Yan Pan, Hongxia Cai, Fang Ye, Wentao Xu, Zhihang Huang, Jingyuan Zhu, Yiwen Gong, Yutong Li, Anastasia Ngozi Ezemaduka, Shan Gao, Shunqi Liu, Guojun Li, Hao Li, Jing Yang, Junyu Ning, Bo Xian","doi":"10.1111/acel.70116","DOIUrl":"https://doi.org/10.1111/acel.70116","url":null,"abstract":"<p><p>Despite the growing interest in developing anti-aging drugs, high costs and low success rates of traditional drug discovery methods pose significant challenges. Aging is a complex biological process associated with numerous diseases, making the identification of compounds that can modulate aging mechanisms critically important. Accelerating the discovery of potential anti-aging compounds is essential to overcome these barriers and enhance lifespan and healthspan. Here, we present ElixirSeeker, a machine learning framework designed to maximize feature capture of lifespan-extending compounds through multi-fingerprint fusion mechanisms. Utilizing this approach, we identified several promising candidate drugs from external compound databases. We tested the top six hits in Caenorhabditis elegans and found that four of these compounds-including Praeruptorin C, Polyphyllin VI, Thymoquinone, and Medrysone-extended the organism's lifespan. This study demonstrates that ElixirSeeker effectively accelerates the identification of viable anti-aging compounds, potentially reducing costs and increasing the success rate of drug development in this field.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70116"},"PeriodicalIF":8.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accumulation of GSK-3β in Interneurons Impairs Adult Hippocampal Neurogenesis by Inhibiting GABAergic Transmission.","authors":"Fei Liu, Jiu-Jing Cui, Xiao-Lin Li, Zeng-Min Zhang, Shao-Hua Liang, Yi Sun, Jing-Min Li, Hong-Lin Qu, Jing Ye, Qi-Peng Guo, Quan Zheng, Yong-Feng Liu","doi":"10.1111/acel.70115","DOIUrl":"https://doi.org/10.1111/acel.70115","url":null,"abstract":"<p><p>The activation of glycogen synthase kinase 3β (GSK-3β) and the deterioration of spatial memory represent prominent pathological and clinical manifestations of Alzheimer's disease (AD). Nevertheless, the precise intrinsic mechanisms linking these pathological features remain poorly elucidated. In this study, we identified significant upregulation of GSK-3β activity in inhibitory interneurons within the hippocampal dentate gyrus (DG) of 3×Tg-AD mice. Subsequent investigations demonstrated that targeted overexpression of GSK-3β in these interneurons triggered aberrant activation of neural stem cells (NSCs), culminating in apoptotic cell death and consequent deficits in adult hippocampal neurogenesis (AHN). Utilizing in vivo fiber-optic recording techniques, we further established that GSK-3β overexpression in DG inhibitory interneurons elicited hyperactivation of excitatory neurons, thereby disrupting the excitation-inhibition (E/I) balance within the DG circuitry. Notably, these pathological alterations were ameliorated through chemogenetic suppression of excitatory neuronal activity. Mechanistically, we determined that impaired GABAergic transmission, characterized by reduced GABA release in the DG region, underlies these observed effects. Pharmacological intervention with GABA receptor agonists effectively rescued AHN impairment and attenuated spatial cognitive deficits. Collectively, these findings demonstrate that GSK-3β overexpression in GABAergic interneurons compromises AHN and promotes NSC apoptosis via disruption of GABAergic signaling, while pharmacological potentiation of GABAergic transmission exerts neuroprotective effects. This study elucidates a previously unrecognized mechanism contributing to AHN impairment in AD and identifies a promising therapeutic target for pro-neurogenic strategies.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70115"},"PeriodicalIF":8.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Effects of Mechanical Loading and Piezo1 Chemical Activation on 22-Months-Old Female Mouse Bone Adaptation.","authors":"Quentin A Meslier, Robert Oehrlein, Sandra J Shefelbine","doi":"10.1111/acel.70087","DOIUrl":"https://doi.org/10.1111/acel.70087","url":null,"abstract":"<p><p>With age, bones mechanosensitivity is reduced, which limits their ability to adapt to loading. The exact mechanism leading to this loss of mechanosensitvity is still unclear, making developing effective treatment challenging. Current treatments mostly focus on preventing bone mass loss (such as bisphosphonates) or promoting bone formation (such as Sclerostin inhibitors) to limit the decline of bones mass. However, treatments do not target the cause of bone mass loss which may be, in part, due to the bone's inability to initiate a normal bone mechanoadaptation response. In this work, we investigated the effects of 2 weeks of tibia loading, and Piezo1 agonist injection in vivo on 22-month-old mouse bone adaptation response. We used an optimized loading profile, which induced high fluid flow velocity and low strain magnitude in adult mouse tibia. We found that tibia loading and Yoda2 injection have an additive effect on increasing cortical bone parameters in 22-month-old mice. In vivo osteocytes calcium signaling imaging suggests that Yoda2 is able to reach osteocytes and activate Piezo1. This combination of mechanical and chemical stimulation could be a promising treatment strategy to help promote bone formation in patients who have low bone mass due to aging.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70087"},"PeriodicalIF":8.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late Life Supplementation of 25-Hydroxycholesterol Reduces Aortic Stiffness and Cellular Senescence in Mice.","authors":"Sophia A Mahoney, Mary A Darrah, Ravinandan Venkatasubramanian, Serban Ciotlos, Matthew J Rossman, Judith Campisi, Douglas R Seals, Simon Melov, Zachary S Clayton","doi":"10.1111/acel.70118","DOIUrl":"https://doi.org/10.1111/acel.70118","url":null,"abstract":"<p><p>Stiffening of the aorta is a key antecedent to cardiovascular diseases (CVD) with aging. Age-related aortic stiffening is driven, in part, by cellular senescence-a hallmark of aging defined primarily by irreversible cell cycle arrest. In this study, we assessed the efficacy of 25-hydroxycholesterol (25HC), an endogenous cholesterol metabolite, as a naturally occurring senolytic to reverse vascular cell senescence and reduce aortic stiffness in old mice. Old (22-26 months) p16-3MR mice, a transgenic model allowing for genetic clearance of p16-positive senescent cells with ganciclovir (GCV), were administered vehicle, 25HC, or GCV to compare the efficacy of the experimental 25HC senolytic versus genetic clearance of senescent cells. We found that short-term (5d) treatment with 25HC reduced aortic stiffness in vivo, assessed via aortic pulse wave velocity (p = 0.002) to a similar extent as GCV. Ex vivo 25HC exposure of aorta rings from the old p16-3MR GCV-treated mice did not further reduce elastic modulus (measure of intrinsic mechanical stiffness), demonstrating that 25HC elicited its beneficial effects on aortic stiffness, in part, through the suppression of excess senescent cells. Improvements in aortic stiffness with 25HC were accompanied by favorable remodeling of structural components of the vascular wall (e.g., lower collagen-1 abundance and higher α-elastin content) to a similar extent as GCV. Moreover, 25HC suppressed its putative molecular target CRYAB, modulated CRYAB-regulated senescent cell anti-apoptotic pathways, and reduced markers of cellular senescence. The findings from this study identify 25HC as a potential therapy to target vascular cell senescence and reduce age-related aortic stiffness.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70118"},"PeriodicalIF":8.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Cognitive Frailty Index for Geriatric Mice.","authors":"Serena Marcozzi, Giorgia Bigossi, Maria Elisa Giuliani, Giovanni Lai, Beatrice Bartozzi, Marta Balietti, Tiziana Casoli, Fiorenza Orlando, Andrea Amoroso, Robertina Giacconi, Maurizio Cardelli, Francesco Piacenza, Fabrizia Lattanzio, Fabiola Olivieri, Peter L J de Keizer, Fabrizio d'Adda di Fagagna, Marco Malavolta","doi":"10.1111/acel.70056","DOIUrl":"https://doi.org/10.1111/acel.70056","url":null,"abstract":"<p><p>Loss of cognitive function is a significant challenge in aging, and developing models to understand and target cognitive decline is crucial for the development of Geroscience-based interventions. Aged mice offer a valuable model as they share features of cognitive decline with humans. Despite numerous studies, knowledge of longitudinal age-related cognitive changes and cognitive frailty in naturally aging mice is limited, particularly in cohorts exceeding 30 months of age, where cognitive decline is more pronounced. Moreover, the impaired physical function of aged mice is known to affect latency-based strategies to measure cognitive performances. Here, we show a comprehensive longitudinal assessment using the Barnes Maze test in a large cohort of 424 aged (≥ 21 months) C57BL/6J mice. We introduced a new metric, the Cognitive Frailty Index (CoFI), which summarizes different age-associated Barnes Maze parameters into a unique function. CoFI strongly associates with advancing age and mortality, offering a reliable ability to discriminate long- and short-lived mice. We also established a CoFI cut-off and a physically adjusted CoFI, both of which can distinguish between physical and cognitive frailty. This is further supported by the enhanced predictive power when physical and cognitive frailty are combined to assess short-term mortality. Moreover, the computation method for CoFI is adaptable to various cognitive assessment tests, leveraging procedures akin to those used for calculating other frailty indices. In conclusion, through robust longitudinal tracking, CoFI has the potential to become an important ally in assessing the effectiveness of Geroscience-based interventions to counteract age-related cognitive impairment.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70056"},"PeriodicalIF":8.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging Compromises Terminal Differentiation Program of Cytotoxic Effector Lineage and Promotes Exhaustion in CD8⁺ T Cells Responding to Coronavirus Infection.","authors":"Ziang Zhu, Guohua Lou, Ying Luo, Kiddist Yihunie, Jonathan Hoar, Juan A Daniel, Bret M Evers, Chen Yao, Tuoqi Wu","doi":"10.1111/acel.70109","DOIUrl":"https://doi.org/10.1111/acel.70109","url":null,"abstract":"<p><p>T cell aging increases the risk of viral infection-related morbidity and mortality and reduces vaccine efficacy in the elderly. A major hallmark of T cell aging is the loss of quiescence and shift toward terminal differentiation during homeostasis. However, how aging impacts the differentiation program of virus-specific T cells during infection is unclear. Here, in a murine coronavirus (MHV) infection model with age-associated increased mortality, we demonstrate that aging impairs, instead of promoting, the terminal differentiation program of virus-specific CD8⁺ T cells. Upon infection, CD8⁺ and CD4⁺ T cells in old mice showed marked reduction in clonal expansion and upregulation of immune checkpoints associated with T cell exhaustion. Bulk and single-cell transcriptomics showed that aging upregulated the T cell exhaustion transcriptional program associated with TOX in virus-specific CD8⁺ T cells and shifted the myeloid compartment from immunostimulatory to immunosuppressive phenotype. In addition, aging downregulated the transcriptional program of terminally differentiated effector CD8⁺ T cells and diminished the CX3CR1⁺ cytotoxic effector lineage. Mechanistically, virus-specific CD8⁺ T cells from infected aged mice displayed defects in inducing transcription factors ZEB2 and KLF2, which were required for terminal differentiation of effector CD8⁺ T cells. Together, our study shows that aging impairs terminal differentiation and promotes exhaustion of virus-specific CD8⁺ T cells responding to coronavirus infection through dysregulating expression of lineage-defining transcription factors.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70109"},"PeriodicalIF":8.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Activity Modifies the Metabolic Profile of CD4⁺ and CD8⁺ T-Cell Subtypes at Rest and Upon Activation in Older Adults.","authors":"Jon Hazeldine, Edward Withnall, Alba Llibre, Niharika A Duggal, Janet M Lord, Amanda V Sardeli","doi":"10.1111/acel.70104","DOIUrl":"https://doi.org/10.1111/acel.70104","url":null,"abstract":"<p><p>T-cell metabolism is a key regulator of immune function. Metabolic dysfunction in T cells from young mice results in an aged phenotype, accelerating immunosenescence. Physical activity (PA) maintains T-cell function and delays immunosenescence in older adults, but the underlying mechanisms are poorly understood. We investigated the effects of PA on the metabolic and functional profiles at a single-cell resolution of resting and stimulated T cells from young adults (N = 9, 23 ± 3 years) and physically active older adults clustered between higher PA (HPA, N = 9, 75.5 ± 4.7 years) or lower PA levels (LPA, N = 10, 76.4 ± 2.1 years). Compared to young donors, HPA older adults had higher mitochondrial dependence (MD) and lower glucose dependence (GD) in unstimulated naïve, central memory (CM) and effector memory (EM) CD4⁺ and EM CD8⁺ T cells, while LPA older adults had higher overall protein synthesis in naïve and EM CD4⁺ and CD8⁺. In response to PMA and Ionomycin stimulation, there was a similar increase in GD and a reduction in MD across groups for most T-cell subsets. Although LPA and HPA underwent a higher increase in protein synthesis upon activation compared to the young subjects, HPA did not exhibit the excessive increase in the percentage of IL-6⁺ T cells observed in the LPA group compared to young subjects. Taken together, our data provide evidence of a higher energy demand, impaired metabolic flexibility, and hyperinflammatory responses in aged T cells, and PA reduces metabolic demand in these cells, potentially through increased MD and improved metabolic flexibility.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70104"},"PeriodicalIF":8.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}