Aging Cell最新文献

{"title":"Extracellular Vesicles From Senescent Cancer Cells Are Necessary and Sufficient to Drive Paracrine Senescence","authors":"Valentin Estevez-Souto,&nbsp;Alex Miralles-Dominguez,&nbsp;Pablo Pedrosa,&nbsp;Patricia Lado-Fernandez,&nbsp;Miguel A. Prados,&nbsp;Alejandro Failde-Fiestras,&nbsp;Raquel Paredes-Paredes,&nbsp;Jorge Ruz-Ortega,&nbsp;Maria J. Alonso,&nbsp;Martina Migliavacca,&nbsp;Ester Polo,&nbsp;Rebeca Alvarez-Velez,&nbsp;Enrique Vazquez de Luis,&nbsp;Ana Dopazo,&nbsp;Gabriela N. Condezo,&nbsp;Carmen San Martin,&nbsp;Miguel Gonzalez-Barcia,&nbsp;Ramón Lobato-Busto,&nbsp;Pilar Ximénez-Embún,&nbsp;Javier Muñoz,&nbsp;Manuel Collado,&nbsp;Sabela Da Silva-Alvarez","doi":"10.1111/acel.70722","DOIUrl":"https://doi.org/10.1111/acel.70722","url":null,"abstract":"<p>Cellular senescence exerts powerful non-cell autonomous effects through the senescence-associated secretory phenotype (SASP). This SASP comprises soluble factors and extracellular vesicles (EVs). Although soluble SASP components can induce senescence in neighboring cells, the specific contribution of EVs to paracrine senescence is poorly defined. Here, we show that EVs released by senescent tumor cells are necessary and sufficient to propagate senescence. Conditioned media from bleomycin-induced senescent A549 cells triggered a growth arrest with morphological changes and upregulation of senescence markers in recipient tumor cells. Pharmacological inhibition of EV biogenesis using GW4869 or genetic downregulation of the EV secretion mediator RAB27A markedly attenuates paracrine senescence without affecting soluble SASP factor secretion or the senescent state of producer cells. Proteomic characterization reveals that senescent EVs exhibit a distinct molecular signature enriched for extracellular components and processes related to wound healing and hemostasis. Importantly, purified senescent EVs, devoid of soluble SASP factors, fully recapitulated paracrine senescence induction. These findings identify senescent EVs as key autonomous SASP effectors and highlight vesicular pathways as potential therapeutic targets in cancer and therapy-induced senescence.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 10","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014700","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":"Mitochondrial Fusion and Fission in Age-Related Cardio-Cerebral Diseases: Mechanisms and Interventions","authors":"Yuyao Yin,&nbsp;Zijian Li","doi":"10.1111/acel.70729","DOIUrl":"https://doi.org/10.1111/acel.70729","url":null,"abstract":"<p>Mitochondria play a crucial role in cellular energy metabolism. The heart and brain require a continuous and stable energy supply. Energy production strongly depends on proper mitochondrial function. Mitochondrial fusion and fission, known as “plasticity”, are vital for maintaining the normal physiological function of cells. Recent studies have shown that impaired mitochondrial dynamics are present in many aging-related diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and atherosclerotic cardio-cerebrovascular disease. The role of impaired mitochondrial dynamics in the pathophysiological process of aging-related diseases is being actively researched. We discovered that targeting proteins related to mitochondrial dynamics, especially those involved in fission and fusion, may offer new treatment strategies for these diseases. Various approaches, including aerobic interval and treadmill training and the use of drugs such as the antidiabetic agents metformin and dapagliflozin, the antihypertensive agent irbesartan, and certain traditional Chinese medicine components, have shown potential in alleviating imbalances in mitochondrial dynamics in aging-related cardio-cerebrovascular diseases. In this review, we systematically summarize recent research on alterations in mitochondrial dynamics in age-related cardio-cerebral diseases and explore therapeutic strategies targeting these alterations, which may offer new directions for improving cardiac and brain health and guiding clinical practice.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 10","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70729","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014697","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":"Associations Between Gut Microbiota and Immune Profiles in Community-Dwelling Older Adults and the Regulatory Role of Polygonatum odoratum","authors":"Tingting Xia,&nbsp;Hongmei Wu,&nbsp;Tianyi Cui,&nbsp;Wenzhi Yang,&nbsp;Min Zhang,&nbsp;Yuhong Huang,&nbsp;Shengyuan Zhou,&nbsp;Yongsheng Wu,&nbsp;Donglan Yan,&nbsp;Fan Jia,&nbsp;Lin Zhang,&nbsp;Zhi Cui,&nbsp;Jiayao An,&nbsp;Xinqin Zhong,&nbsp;Bin Lv,&nbsp;Xin Zhao,&nbsp;Kaijun Niu,&nbsp;Xiumei Gao","doi":"10.1111/acel.70724","DOIUrl":"https://doi.org/10.1111/acel.70724","url":null,"abstract":"<p>Aging is often associated with intestinal microbiota imbalance and immune system degeneration. The dysregulation and crosstalk of these two factors markedly elevate the elderly's susceptibility to infections and age-related diseases. <i>Polygonatum odoratum</i>, a traditional Chinese medicinal herb, is widely used in geriatric care for its lung-moistening and nourishing effects. However, its potential regulatory roles on the microbiota and immunity in the aging context remain unreported. A total of 140 independently living elderly individuals aged 60 and above were recruited for this study. The randomized, double-blinded study including YZG (<i>P. odoratum</i>) and placebo groups was performed for 90 days' intervention. Peripheral blood immune cell subsets were analyzed by flow cytometry, and microbial diversity in fecal samples was assessed by 16S rRNA sequencing. Baseline correlation analysis revealed that alterations in gut microbiota were predominantly associated with T cell subsets. Specifically, <i>Akkermansia</i> showed a significant negative correlation with age-related memory T cells, including CD4⁺ and CD8⁺ TEMRA. Additionally, <i>Klebsiella</i> exhibited a significant positive correlation with partial subsets of CD4⁺ TEMRA. After 90-day YZG intervention, the percentage of TEMRA and CD28⁻ CD57⁺ TEMRA cells were reduced in elderly subjects. The relative abundance of <i>Prevotella 9</i> and <i>Akkermansia</i> were increased, and the abundance of <i>Klebsiella</i> in the gut microbiota were significantly decreased. Correlation analysis linked YZG-induced gut microbiota changes to improved immunity and fewer respiratory infections. This study demonstrates significant correlations that exist between immunosenescence in T-cell compartments and gut microbial composition, suggesting a potential interplay between microbial health and immune aging.</p><p><b>Trial Registration:</b> UMIN Clinical Trials Registry identifier: UMIN000052572</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 10","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014802","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":"Transplantation of Elderly Human Gut Microbiota Into Pigs Reprograms Intestinal Barrier Function, Plasma Metabolome, and Gut Mucosal Transcriptomic Landscape","authors":"Jiaxin Wang,&nbsp;Lingyu Li,&nbsp;Lihua Mei,&nbsp;Zhining Tang,&nbsp;Baorui Liao,&nbsp;Qianye Zhao,&nbsp;Yuzeng Wang,&nbsp;Qingyao Fu,&nbsp;Liu Ren,&nbsp;Zhian Zhai,&nbsp;Yifei Xu,&nbsp;Aoyu Yang,&nbsp;Shuai Duan,&nbsp;Zhengyuan Zhai,&nbsp;Yanling Hao,&nbsp;Yalin Zhou,&nbsp;Yajun Xu,&nbsp;Ying Yang,&nbsp;Zhenlong Wu,&nbsp;Yun Ji","doi":"10.1111/acel.70725","DOIUrl":"https://doi.org/10.1111/acel.70725","url":null,"abstract":"<p>The gut microbiota plays a pivotal role in maintaining intestinal homeostasis and regulating host metabolism, yet its composition and function undergo substantial alterations with aging. However, the relationship between age-associated microbial changes and host intestinal physiology remains not fully elucidated. Here, we employed Bama miniature pigs, a model with close gastrointestinal similarity to humans, to investigate the impact of fecal microbiota transplantation (FMT) from young or elderly human donors on gut structure, barrier integrity, plasma metabolites, and intestinal mucosal transcriptomics. FMT resulted in distinct gut microbial profiles, with elderly-donor FMT reducing ileal villus height and tight junction proteins (ZO-1, claudin-1, and occludin) across multiple intestinal segments. At the species level, <i>Phocea massiliensis</i> predominated in young-donor pigs, while <i>Blautia obeum</i> was enriched in elderly-donor pigs. Plasma metabolomic analysis revealed increased 3-methyloxindole, prostaglandin E3, and 2-hydroxybutanoic acid but reduced Tyr-Phe and 2-hydroxyoctadecanoic acid in the elderly group. Among <i>B. obeum</i>-associated metabolites, Tyr-Phe and 2-hydroxyoctadecanoic acid exhibited a positive correlation with certain intestinal tight junction protein levels, whereas prostaglandin E3 showed an inverse correlation. Further validation performed in IPEC-1 cells demonstrated that Tyr-Phe elevated transepithelial electrical resistance (TEER), while prostaglandin E3 lowered this parameter. Transcriptomic profiling identified seven hub genes (<i>MX2</i>, <i>ISG15</i>, <i>IFI6</i>, <i>IFIT1</i>, <i>OAS1</i>, <i>DHX58</i>, <i>ISG12(A)</i>) that were consistently downregulated in the ileal mucosa of pigs receiving elderly-donor microbiota. These findings link age-associated microbiota alterations to coordinated changes in intestinal architecture, barrier integrity, and host metabolic and transcriptional profiles, providing insights into microbial and metabolic features associated with age-related intestinal decline.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 10","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014695","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":"Integrative Analysis Uncover the Effects and Multi-Omics Features of Thigh Muscle Fat Infiltration","authors":"Yiwei Zhang,&nbsp;Qin Dang,&nbsp;Xizeng Zong,&nbsp;Haowei Chen,&nbsp;Simin Wen,&nbsp;Siqi Xu,&nbsp;Kunyan Wang,&nbsp;Xiaoshuai Wang,&nbsp;Jianwei Zhu,&nbsp;Zhaohua Zhu,&nbsp;Changhai Ding,&nbsp;Guangfeng Ruan,&nbsp;Yan Zhang","doi":"10.1111/acel.70690","DOIUrl":"10.1111/acel.70690","url":null,"abstract":"<p>The health impacts and underlying biological pathways of thigh muscle fat infiltration (TMFI) remain incompletely understood. In this study, we analyzed TMFI measured by magnetic resonance imaging in 55,120 UK Biobank participants and found that higher TMFI was significantly associated with all-cause mortality as well as with all major system-specific diseases examined (<i>p</i> values ranged from 2.50 × 10⁻⁸⁸ to 9.97 × 10⁻⁰⁴). TMFI also mediated the effects of lifestyle factors on health-related outcomes, with mediation proportions ranging from 6.7% to 71.7%. A genome-wide association study (GWAS) identified 79 lead single nucleotide polymorphisms (SNPs) linked to TMFI, and the polygenic risk score for TMFI was significantly associated with mortality and all incident diseases across examined organ systems in an independent subset of UK Biobank participants of European ancestry who were not included in the TMFI GWAS (<i>n</i> = 362,286, all <i>p</i> &lt; 0.05). Gene–drug interactions identified multiple drugs that could potentially modulate TMFI. Analysis of single-cell transcriptomic data indicated that myogenic cells were strongly linked to TMFI (<i>p</i> = 7.08 × 10⁻⁰⁸). Summary-data-based Mendelian randomization and Transcriptome-Wide Association Study analyses revealed numerous genes whose expression in specific tissues was associated with TMFI. Proteomic and metabolomic profiling uncovered a broad array of circulating biomarkers associated with TMFI, many of which mediated the effects of modifiable factors and genetic risk on TMFI. Overall, our results highlight the biological relevance of TMFI to human health and provide insights into the multi-omics mechanisms underlying TMFI, identifying potential targets for interventions.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 9","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862695","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":"Oxygenaging: A Physiological Framework for Geroscience","authors":"Stefano Donega,&nbsp;Kenneth W. Fishbein,&nbsp;Paolo Dominelli,&nbsp;Allison B. Herman,&nbsp;Rafael de Cabo,&nbsp;Myriam Gorospe,&nbsp;Luigi Ferrucci","doi":"10.1111/acel.70664","DOIUrl":"10.1111/acel.70664","url":null,"abstract":"<p>The stepwise movement of oxygen from the atmosphere to the mitochondria, the “oxygen cascade”, is one of the most tightly regulated systems in physiology. Despite decades of mechanistic study, it has remained quite unexplored in Geroscience. This oversight should be reconsidered. In young organisms, hypoxic stress (whether environmental or tissue-specific) activates a complex adaptive response to preserve energetic stability via restraining anabolic pathways, optimizing mitochondrial performance, and reinforcing cellular quality control systems. With advancing age, angiostatic signaling increases, endothelial metabolism becomes dysregulated, and overall alveolar ventilation and pulmonary gas exchange (ventilation–perfusion matching and diffusion capacity) become less efficient. These changes promote microvascular rarefaction and low-grade but persistent mismatches between oxygen delivery and demand at the tissue level, ultimately destabilizing cellular function. In this review, we propose that the gradual erosion of oxygen homeostasis is not simply a byproduct of aging, but also a driver of molecular damage and functional decline. We examine the aging oxygen cascade through the framework of resilience biology, focusing on mechanisms such as mitochondrial electron leaks, oxidative stress amplification, iron dyshomeostasis, ferroptosis, and epigenetic remodeling. We also discuss interventions that alter oxygen availability, such as intermittent hypoxia, hyperbaric oxygen therapy, and hypoxic–hyperoxic training. These approaches demonstrate adaptive potential, but they also highlight the narrow margin between beneficial stress and injury. We propose “Oxygenaging” as a unifying framework in which aging associates with the progressive loss of equilibrium across the oxygen cascade, linking systemic oxygen transport to mitochondrial function, genomic stability, and cellular resilience.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 9","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70664","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838570","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":"Shelterin TPP1 Promotes Hair Regeneration Through Activating Bulge Hair Follicle Stem Cells","authors":"Lihui Wang,&nbsp;Bihan Zhao,&nbsp;Jiahui Yang,&nbsp;Ying Liang,&nbsp;Yitian Yao,&nbsp;Xiao Xiao,&nbsp;Long Yang,&nbsp;Jinghao Xia,&nbsp;Haoze Li,&nbsp;Ling Gao,&nbsp;Jun Zhang,&nbsp;Tianci Su,&nbsp;Hao Xu,&nbsp;Jiacheng Zhang,&nbsp;Hongyan Wang,&nbsp;Jun Liu,&nbsp;Xiaojing Hong,&nbsp;Jun-Ping Liu","doi":"10.1111/acel.70692","DOIUrl":"10.1111/acel.70692","url":null,"abstract":"<p>Telomere shortening drives hair follicle senescence, yet successful reversal of this aging process has remained elusive. Here, we report that stem cell overexpression of <i>Acd</i>, the gene encoding TPP1 (telomere protection protein 1)—a shelterin component that recruits telomerase—accelerates hair regeneration in mice. Stabilization of TPP1 protein via topical application of TELODIN, a synthetic octapeptide that inhibits TPP1 degradation, similarly promotes hair regeneration. Mechanistically, increased TPP1 mobilizes bulge hair follicle stem cells (bHFSCs) by coordinating telomere capping and telomerase recruitment. By facilitating the synchronization and transition of hair follicles from the quiescent telogen phase to the proliferative anagen phase, TPP1 drives bHFSCs proliferation, differentiation, and migration. These findings identify TPP1 as a master regulator of hair regeneration through telomere capping and elongation, and suggest that topical TELODIN represents a novel therapeutic strategy for advancing hair growth. This work establishes a therapeutic framework for telomere-targeted interventions against alopecia.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 9","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70692","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838617","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":"A Mechanism-Based Framework for Anti-Aging Strategies: From Metabolic Regulation to Senotherapy and Stem Cell-Based Interventions","authors":"Feifei Li,&nbsp;Yankai Wang,&nbsp;Gelin Wang,&nbsp;Jiguo Chen,&nbsp;Song Huang","doi":"10.1111/acel.70658","DOIUrl":"10.1111/acel.70658","url":null,"abstract":"<p>The global prevalence of aging and age-related diseases has increased markedly in recent decades due to extended life expectancy and a growing aging population, posing substantial medical and social burdens. Multiple strategies, including metabolic modulation (e.g., physical exercise, calorie restriction, and calorie restriction mimetics), targeting inflammaging, senotherapy, parabiosis, stem cell-based therapies, and epigenetic rejuvenation, have shown promise in slowing aging and extending lifespan in preclinical models, with some demonstrating efficacy in clinical trials. This review summarizes the current status of leading anti-aging interventions, their clinical progress, and the underlying mechanisms, which include enhancing autophagy, clearing senescent cells and supporting mitochondrial function to reduce chronic inflammation. We propose that metabolic modulation, inflammaging control, and senotherapy constitute three interconnected pillars of contemporary anti-aging strategies.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 9","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70658","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838582","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":"Timing-Dependent Clearance of p16-Positive Cells Mitigates Radiation-Induced Accelerated Aging","authors":"Karla Valdivieso,&nbsp;Melanie Weigand,&nbsp;Daniela G. Costa,&nbsp;Gung Lee,&nbsp;Nick Pirius,&nbsp;Helene Martini,&nbsp;Shivangi Oberai,&nbsp;Christina Inman,&nbsp;Yi Zhu,&nbsp;Thomas von Zglinicki,&nbsp;Sundeep Khosla,&nbsp;Nathan LeBrasseur,&nbsp;João F. Passos,&nbsp;Tamara Tchkonia,&nbsp;James L. Kirkland,&nbsp;Diana Jurk","doi":"10.1111/acel.70693","DOIUrl":"10.1111/acel.70693","url":null,"abstract":"<p>Genotoxic stress induced by cancer therapies is increasingly recognized as a driver of accelerated aging in long-term cancer survivors, yet the mechanisms responsible for the emergence of age-related dysfunction months to years after treatment remain poorly understood. Here, we use sublethal whole-body irradiation as a model of systemic genotoxic stress to test whether senescent cells contribute to the progression of post-therapy age-related dysfunction and whether the benefits of senescent cell clearance depend on the timing of intervention. Using the <i>INK-ATTAC</i> mouse model, we selectively eliminated p16^Ink4a-positive cells either early (1 month) or later (4 months) after irradiation. Early clearance had no effect on lifespan or functional outcomes. In contrast, delayed clearance markedly reduced frailty, improved neuromuscular and cognitive function, restored blood–brain barrier integrity, improved hepatic metabolic dysfunction, and increased median survival, with the survival benefit being most evident in female mice. Mechanistically, irradiation induced an early p21^Cip1-associated stress response and later accumulation of p16^Ink4a-positive cells in the brain and liver, which was associated with inflammation and tissue dysfunction. Clearance of p16^Ink4a-positive cells at the later stage attenuated these changes. Together, these findings identify p16^Ink4a-positive cells as key drivers of the radiation-induced accelerated aging-like state that emerges progressively after genotoxic stress. They also show that the efficacy of senescence-targeted interventions depends on when treatment is initiated, with implications for improving long-term outcomes in cancer survivors.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 9","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70693","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823825","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":"Associations Between Accelerometer-Assessed Sleep Patterns, Proteomic Signatures, and Hallmarks of Aging in Adulthood","authors":"Ruiyi Liu,&nbsp;Jingsong Luo,&nbsp;Yangchang Zhang,&nbsp;Furong Wang,&nbsp;Jing Xu,&nbsp;Wangnan Cao,&nbsp;Shengzhi Sun","doi":"10.1111/acel.70685","DOIUrl":"10.1111/acel.70685","url":null,"abstract":"<p>The associations between objectively measured sleep patterns, the hallmarks of aging, and their shared proteomic signatures remain poorly understood. In this study, we utilized wrist-worn accelerometer data, plasma proteomic profiles, and health records from the UK Biobank to examine the associations between six defined sleep patterns and nine established hallmarks of aging. We further identified proteins jointly associated with both sleep patterns and aging hallmarks. Longer total sleep duration, greater deep sleep, and increased rapid eye movement (REM) sleep were associated with lower risk of most aging hallmarks. In contrast, higher wakefulness after sleep onset (WASO) and greater sleep irregularity were associated with higher risk, whereas light sleep showed no significant associations. The number of overlapping proteins varied substantially across sleep-hallmark associations, ranging from 1 to 558. These proteins were predominantly enriched in immune and inflammatory pathways. Several proteins, including IL1RN, FABP1, GDF15, and LEP, were consistently observed across multiple sleep patterns and aging hallmarks. These findings may help generate hypotheses about shared underlying biological processes between sleep and the aging process.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 9","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70685","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823800","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}