Aging Cell最新文献

{"title":"Profiling Epigenetic Aging at Cell-Type Resolution Through Long-Read Sequencing","authors":"Alec Eames,&nbsp;Mahdi Moqri,&nbsp;Jesse R. Poganik,&nbsp;Vadim N. Gladyshev","doi":"10.1111/acel.70084","DOIUrl":"10.1111/acel.70084","url":null,"abstract":"<p>DNA methylation can give rise to robust biomarkers of aging, yet most studies profile it at the bulk tissue level, which masks cell type-specific alterations that may follow distinct aging trajectories. Long-read sequencing technology enables methylation profiling of extended DNA fragments, enabling mapping to their cell type of origin. In this study, we introduce a framework for evaluating cell type-specific aging using long-read sequencing data, without the need for cell sorting. Leveraging cell type-specific methylation patterns, we map long-read fragments to individual cell types and generate cell type-specific methylation profiles, which are used as input to a newly developed probabilistic aging model, LongReadAge, capable of predicting epigenetic age at the cell type level. We use LongReadAge to track aging of myeloid cells and lymphocytes from bulk leukocyte data as well as circulating cell-free DNA, demonstrating robust performance in predicting age despite limited shared features across samples. This approach provides a novel method for profiling the dynamics of epigenetic aging at cell type resolution.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 8","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537538","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":"Identification of Functional Cellular Markers Related to Human Health, Frailty and Chronological Age","authors":"Chloé Brodeau,&nbsp;Camille Joly,&nbsp;Anaïs Chekroun,&nbsp;Jean Nakhle,&nbsp;Vincent Blase,&nbsp;Nicolas Espagnolle,&nbsp;Cédric Dray,&nbsp;Armelle Yart,&nbsp;Valérie Planat,&nbsp;Margot Tertrais,&nbsp;Julien Fassy,&nbsp;Sophie Guyonnet,&nbsp;Wan-Hsuan Lu,&nbsp;Philipe de Souto Barreto,&nbsp;Olivier Teste,&nbsp;Marie Tremblay-Franco,&nbsp;Kamaryn T. Tanner,&nbsp;Alan A. Cohen,&nbsp;Audrey Carriere,&nbsp;Louis Casteilla,&nbsp;Isabelle Ader,&nbsp;IHU HealthAge/Open Science group","doi":"10.1111/acel.70153","DOIUrl":"10.1111/acel.70153","url":null,"abstract":"<p>Aging leads to a decline in physiological reserves, an increase in age-related diseases, reduced functional ability and a shortened healthspan. While molecular markers of chronological aging exist, their link to general health and intrinsic capacity (IC), a composite measure of physical and mental capacities, remains unclear. This study integrates the WHO's Healthy Aging framework with geroscience to explore fibroblasts as indicators of health. We assessed primary skin fibroblasts from 133 individuals aged 20–96, evaluating their ability to maintain tissue structure, modulate immune responses and regulate metabolism (SIM functions). By combining functional and molecular analyses, we investigated the relationship between fibroblast performance, chronological age and IC. Our results demonstrate that fibroblast SIM functions are modified with stressors and age, correlating with IC rather than just chronological age. Notably, fibroblasts from pre-frail and frail individuals exhibited reduced mitochondrial respiration and lower extracellular periostin levels, with periostin being able to capture IC status, irrespective of age and sex, reflecting a cellular ‘health memory’. The SIM paradigm provides a complementary framework to the established hallmarks of aging, advancing our understanding of how cellular aging impacts functional decline. These findings suggest that fibroblast-derived markers could serve as indicators of frailty and reduced IC, enabling early detection of individuals at risk for health deterioration and laying the foundation for early identification of functional decline.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 9","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537537","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":"Altered Relaxation and Mitochondria-Endoplasmic Reticulum Contacts Precede Major (Mal)Adaptations in Aging Skeletal Muscle and Are Prevented by Exercise","authors":"Ryan J. Allen,&nbsp;Ana Kronemberger,&nbsp;Qian Shi,&nbsp;R. Marshall Pope,&nbsp;Elizabeth Cuadra-Muñoz,&nbsp;Wangkuk Son,&nbsp;Long-Sheng Song,&nbsp;Ethan J. Anderson,&nbsp;Renata O. Pereira,&nbsp;Vitor A. Lira","doi":"10.1111/acel.70137","DOIUrl":"10.1111/acel.70137","url":null,"abstract":"<p>Sarcopenia, or age-related muscle dysfunction, contributes to morbidity and mortality. Besides decreases in muscle force, sarcopenia is associated with atrophy and fast-to-slow fiber type switching, which is typically secondary to denervation in humans and rodents. However, very little is known about cellular changes preceding these important (mal)adaptations. To this matter, mitochondria and the sarcoplasmic reticulum are critical for tension generation in myofibers. They physically interact at the boundaries of sarcomeres, forming subcellular hubs called mitochondria-endo/sarcoplasmic reticulum contacts (MERCs). Yet, whether changes at MERCs ultrastructure and proteome occur early in aging is unknown. Here, studying young adult and older mice, we reveal that aging slows muscle relaxation, leading to longer excitation-contraction-relaxation (ECR) cycles before maximal force decreases and fast-to-slow fiber switching takes place. We also demonstrate that muscle MERC ultrastructure and mitochondria-associated ER membrane (MAM) protein composition are affected early in aging and are closely associated with the rate of muscle relaxation. Additionally, we demonstrate that regular exercise preserves muscle relaxation rate and MERC ultrastructure in early aging. Finally, we profile a set of muscle MAM proteins involved in energy metabolism, protein quality control, Ca²⁺ homeostasis, cytoskeleton integrity, and redox balance that are inversely regulated early in aging and by exercise. These may represent new targets to preserve muscle function in aging individuals.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 9","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525664","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":"Patient-Derived Cortical Organoids Reveal Senescence of Neural Progenitor Cells in Hutchinson-Gilford Progeria Syndrome","authors":"Seeun Jeon,&nbsp;Chul-Sung Park,&nbsp;Juyoung Hong,&nbsp;Jieun Kim,&nbsp;Yun Jin Lee,&nbsp;Junho K. Hur,&nbsp;Ji Yeoun Lee","doi":"10.1111/acel.70143","DOIUrl":"10.1111/acel.70143","url":null,"abstract":"<p>Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by premature aging and primarily caused by the accumulation of progerin, a mutant form of lamin A. Although the effects of progerin on multiple tissues have been previously studied, its impact on brain development is not completely understood. We established cortical organoids derived from HGPS patient-induced pluripotent stem cells (iPSCs) from patients with HGPS to investigate the role of progerin in the brain. HGPS cortical organoids showed hallmarks of HGPS pathology, including elevated progerin expression and irregular nuclear morphology during early developmental stages. Additionally, we observed abnormal morphology and increased cellular senescence specifically in the rosette regions of HGPS organoids. This senescence appeared to interfere with normal neuronal differentiation, resulting in a significant reduction in mature neuron development and synapse formation in HGPS cortical organoids. Transcriptome profiling of HGPS cortical organoids revealed the downregulation of key genes related to neural development and synapse formation, with these changes persisting over time, potentially contributing to impaired neuronal differentiation and maturation. These findings suggest the role of progerin in early neural development and establish cortical organoids as a model for studying HGPS-related brain development.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 9","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525667","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":"Impaired Cytokine Secretion Contributes to Age-Dependent Immune Dysfunction in SARS Coronavirus Response and Is Restored by Young CD11b-Positive Cell Transfer","authors":"Yu-Xuan Wu,&nbsp;Chih-Wei Hu,&nbsp;Jui-Yu Chang,&nbsp;Shuoh-Wen Chen,&nbsp;Ting-An Lin,&nbsp;Eric Chang-Yi Lin,&nbsp;Min-Hui Chen,&nbsp;Chuen-Mi Yang,&nbsp;Hsuan-Ying Lu,&nbsp;Ching-Jung Teng,&nbsp;Yuan-I Chang","doi":"10.1111/acel.70154","DOIUrl":"10.1111/acel.70154","url":null,"abstract":"<p>COVID-19 mortality disproportionately affects the elderly, yet the cellular and molecular factors contributing to age-related immune system remodeling remain unclear. Using SARS-CoV-derived ssRNA sequences, we modeled age-dependent immune responses in mice. Aged mice exhibited higher mortality and severe lung inflammation upon viral ssRNA challenge, mirroring clinical observations. We uncovered a pre-existing inflammatory state in aged mice, characterized by elevated baseline levels of specific immune cells and cytokines correlating with poor outcomes. Age-related immune dysfunction stemmed from impaired IRF7 signaling and defective SNARE-mediated cytokine secretion in CD11b⁺ cells. Notably, the adoptive transfer of young CD11b⁺ cells to aged mice exposed to SARS-CoV2 ssRNA reduced mortality, alleviated lung inflammation, and normalized cytokine profiles. These findings provide insights into age-related immune dysregulation during viral challenges and suggest potential therapeutic strategies for severe COVID-19 in the elderly.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 9","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525666","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":"Avian Lifespan Network Reveals Shared Mechanisms and New Key Players in Animal Longevity","authors":"Mirko Martini,&nbsp;Giovanni Piccinini,&nbsp;Liliana Milani,&nbsp;Mariangela Iannello","doi":"10.1111/acel.70156","DOIUrl":"10.1111/acel.70156","url":null,"abstract":"<p>Lifespan is a highly variable life trait across the Tree of Life, governed by complex and multifactorial mechanisms. While some conserved pathways regulating longevity have been identified in various species, the molecular basis of this phenotype is far from being understood. In this context, the adoption of new model species and methods of investigation may offer opportunities to explore the molecular underpinnings of longevity in animals. In this study, we investigated the genomic resources of 141 birds to analyze the molecular evolution underlying extremely long- and short lifespans. We show that birds with similar lifespans exhibit convergent evolution in specific genes regardless of body mass and phylogenetic relationship, enabling the construction of a “lifespan network” of protein–protein interactions. This network highlights the interplay between metabolism and cell cycle control as key processes in avian lifespan regulation. This lifespan network not only provides evidence for shared mechanisms of lifespan regulation across different organisms but also enables the identification of new candidates for studying aging, particularly in humans. By integrating multiple evolutionary signals from both extremes of the lifespan distribution, our results show the power of evolutionary and comparative approaches in studying complex traits like longevity, providing new insights into aging research.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 9","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525665","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":"Microbiological Foundations to Optimise Intrinsic Capacity and Promote Healthy Ageing: An Integration Into the Life Course Approach","authors":"Christoph Benner,&nbsp;Matteo Cesari,&nbsp;Ritu Sadana","doi":"10.1111/acel.70146","DOIUrl":"10.1111/acel.70146","url":null,"abstract":"<p>The World Health Organization (WHO) defines healthy ageing as the process of developing and maintaining functional ability, comprising an individual's intrinsic capacity, the environment and the interaction of the two. The framework is based on a positive approach to ageing, giving value to the resources individuals can rely upon as they age and that they can build their physical, mental and social health, and overall well-being. To promote healthy ageing, it is important to understand better the biological mechanisms underlying this phenomenon from this positive perspective. Our knowledge about cellular processes that drive human ageing has increased dramatically, with current evidence identifying 12 hallmarks of ageing. Dysbiosis is one of these and is broadly defined as a ‘deranged microbiological composition in and on the human body’. It is often measured by quantitatively and qualitatively evaluating the bacterial species in the gut. A major feature of dysbiosis and other markers of ageing is that these focus on age-related impairments, contributing to the onset of adverse outcomes over time rather than highlighting features that promote healthy ageing. Scientific literature addressing the hallmarks of healthy ageing, including those potentially positively affecting intrinsic capacity, is lacking. To this end, we propose the concept of gut eubiosis, the homeostatic state of commensal gut bacteria and their metabolites, as proof of concept, serving as a hallmark of healthy ageing. Importantly, this work adopts a life course approach to explore how a person's intrinsic capacities evolve with gut microbiota modifications at different life stages.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 8","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504311","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":"Correction to “Multiple Outcomes of the Germline p16INK4a Mutation Affecting Senescence and Immunity in Human Skin”","authors":"","doi":"10.1111/acel.70157","DOIUrl":"10.1111/acel.70157","url":null,"abstract":"<p>Subramanian, P., Sayegh, S., Laphanuwat, P., Devine, O. P., Fantecelle, C. H., Sikora, J., Chambers, E. S., Karagiannis, S. N., Gomes, D. C. O., Kulkarni, A., Rustin, M. H. A., Lacy, K. E., &amp; Akbar, A. N. (2025). Multiple outcomes of the germline p16^INK4a mutation affecting senescence and immunity in human skin. <i>Aging Cell</i>, 24, e14373.</p><p>In the “Acknowledgements” section the text “We thank Hugh Trahair for his technical support with sectioning skin blocks. We also thank Dr. Rajni Sharma helping to set up the in vitro senescence assay” is incomplete. This should have read “We thank Hugh Trahair for his technical support with sectioning skin blocks, Dr Zena Willsmore for obtaining donor information, and Histopathology colleagues at Guy's and St Thomas' Hospital for their support with sectioning patient blocks. We also thank Dr. Rajni Sharma for helping to set up the in vitro senescence assay.”</p><p>We apologize for this error.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 8","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504310","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":"SIRT1 Prevents Lens Epithelial Cell Senescence During Age-Related Cataract via Regulating p66Shc","authors":"Huirui Liu,&nbsp;Liyao Sun,&nbsp;Yu Mi,&nbsp;Yi Gao,&nbsp;Jialin Luo,&nbsp;Fengchun Kang,&nbsp;Yujing Bai,&nbsp;Xiaohan Yu,&nbsp;Hongyan Ge","doi":"10.1111/acel.70155","DOIUrl":"10.1111/acel.70155","url":null,"abstract":"<p>Lens epithelial cell (LEC) senescence is one of the key pathological processes of age-related cataract (ARC) and is associated with oxidative stress, mitochondrial dysfunction, and protein aggregation. This study aimed to elucidate the pathogenesis of LEC senescence in ARC. The protein expression level of silencing regulatory protein 1 (SIRT1) and aptamer protein (p66Shc) was quantified. Reactive oxygen species (ROS) and mitochondrial superoxide levels were measured to evaluate cellular oxidative stress. Senescence-associated protein expression (p21 and p53) and SA-β-galactosidase staining were employed to assess the aging status of LEC. Targeted metabolic analysis was conducted to explore energy changes during LEC senescence, and mitochondrial morphology and function were assessed in the cell models. The aging and damage conditions of the lens in ARC rats were evaluated through histological staining, transmission electron microscopy, expression of senescence-related proteins, and oxidative stress markers. We comprehensively investigated the downregulation of SIRT1 expression and the upregulation of p66Shc expression in human cataract samples, UVB-induced rat cataract models, and UVB-treated LEC. SIRT1 could alleviate UVB-induced oxidative stress, as well as mitochondrial dysfunction, inhibiting p66Shc expression in LEC. Nicotinamide mononucleotide (NMN) effectively alleviated the abnormal expression of aging-related proteins and inhibited mitochondrial morphological and functional disorders by activating SIRT1. In conclusion, NMN activated SIRT1, inhibiting mitochondrial dysfunction, oxidative stress, and senescence in LEC, delaying lens opacity. This mechanism could be associated with the onset and progression of ARC, providing a new strategy for its prevention and treatment.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 9","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493254","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":"CD38-Targeting Peptide Vaccine Ameliorates Aging-Associated Phenotypes in Mice","authors":"Shangcheng Yu,&nbsp;Zhiqiang Li,&nbsp;Yuxiang Tang,&nbsp;Yuling Chen,&nbsp;Yingying Ma,&nbsp;Kunlin Du,&nbsp;Zhaoyun Zong,&nbsp;Kangze Feng,&nbsp;Yali Wei,&nbsp;Limeng Chen,&nbsp;Haiteng Deng","doi":"10.1111/acel.70147","DOIUrl":"10.1111/acel.70147","url":null,"abstract":"<p>Antiaging vaccines have recently been found to elicit long-term benefits in slowing the aging process. Meanwhile, high CD38 expression in organs is an aging characteristic contributing to a decreased NAD⁺/NADH ratio. Thus, in the current study, we systematically investigate the effects of a CD38-targeting peptide vaccine (CD38-vaccine) on aging-associated phenotypes in mice. The CD38-vaccine induces a robust T-cell immune response, selectively depletes CD38⁺ myeloid cells in the spleen, and ameliorates age-related physical and cognitive function decline. Metabolically, vaccination improves glucose tolerance, enhances oxygen consumption, and decreases the number of senescent cells and mRNA levels of senescence-related genes in liver tissues. Vaccination also increases the NAD⁺/NADH ratio in the liver tissues, enhances oxidative metabolism, and reduces glycolysis. These findings indicate that targeting CD38 via vaccination is a promising strategy for ameliorating aging-associated phenotypes.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 9","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482591","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}