Nature aging最新文献_第5页

Oxidative stress response protein delays ovarian aging by promoting stress granule clearance 氧化应激反应蛋白通过促进应激颗粒清除延缓卵巢衰老。

IF 19.4

Nature aging Pub Date : 2025-08-27 DOI: 10.1038/s43587-025-00960-9

引用次数: 0

Mevalonate metabolites boost aged oocyte quality through prenylation of small GTPases. 甲羟戊酸代谢物通过小gtp酶的戊烯酰化提高衰老的卵母细胞质量。

IF 19.4

Nature aging Pub Date : 2025-08-26 DOI: 10.1038/s43587-025-00946-7

Chuanming Liu, Huidan Zhang, Jialian Mao, Sainan Zhang, Xiao Tian, Yibing Zhu, Changjiang Wang, Junshun Fang, Huijie Pan, Nannan Kang, Yang Zhang, Jidong Zhou, Xin Zhen, Guijun Yan, Chaojun Li, Yali Hu, Cunqi Ye, Ran Xie, Chun So, Haixiang Sun, Lijun Ding

{"title":"Mevalonate metabolites boost aged oocyte quality through prenylation of small GTPases.","authors":"Chuanming Liu, Huidan Zhang, Jialian Mao, Sainan Zhang, Xiao Tian, Yibing Zhu, Changjiang Wang, Junshun Fang, Huijie Pan, Nannan Kang, Yang Zhang, Jidong Zhou, Xin Zhen, Guijun Yan, Chaojun Li, Yali Hu, Cunqi Ye, Ran Xie, Chun So, Haixiang Sun, Lijun Ding","doi":"10.1038/s43587-025-00946-7","DOIUrl":"https://doi.org/10.1038/s43587-025-00946-7","url":null,"abstract":"Declining oocyte quality is the major contributor to female subfertility in aged mammals. Currently, there are no effective interventions to ameliorate aged oocyte quality. Here we found that oocytes at metaphase I from the cumulus-oocyte complexes of aged mice showed reduced cortical F-actin and lower levels of mevalonate (MVA) pathway metabolites, including MVA, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate. We further showed that MVA supplementation improved FPP levels, cortical F-actin and the quality of aged oocytes. Mechanistically, we found that MVA supplementation induced granulosa cells to synthesize FPP, which was subsequently transferred to aged oocytes. Transported FPP increased the prenylation of small GTPases, including CDC42 and RAC1, and promoted membrane localization of CDC42-N-WASP-Arp2/3 and RAC1-WAVE2-Arp2/3 complexes, promoting cortical F-actin reassembly and reducing aneuploidy of aged oocytes. We also identified a natural chemical compound, 8-isopentenyl flavone, with an isopentenyl side chain from Epimedium brevicornu Maxim, which could increase CDC42 and RAC1 prenylation, improving the cortical F-actin and the competence of aged oocytes, and ameliorating reproductive outcomes in aged female mice. Collectively, increasing the prenylation of small GTPases via MVA metabolites or 8-isopentenyl flavone provides a therapeutic approach for boosting female fertility during reproductive aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasma tau biomarkers for biological staging of Alzheimer's disease. 血浆tau生物标志物用于阿尔茨海默病的生物学分期。

IF 19.4

Nature aging Pub Date : 2025-08-22 DOI: 10.1038/s43587-025-00951-w

Laia Montoliu-Gaya, Gemma Salvadó, Joseph Therriault, Johanna Nilsson, Shorena Janelidze, Sophia Weiner, Nicholas J Ashton, Andrea L Benedet, Nesrine Rahmouni, Juan Lantero-Rodriguez, Niklas Mattsson-Carlgren, Sebastian Palmqvist, Gunnar Brinkmalm, Erik Stomrud, Henrik Zetterberg, Johan Gobom, Pedro Rosa-Neto, Kaj Blennow, Oskar Hansson

{"title":"Plasma tau biomarkers for biological staging of Alzheimer's disease.","authors":"Laia Montoliu-Gaya, Gemma Salvadó, Joseph Therriault, Johanna Nilsson, Shorena Janelidze, Sophia Weiner, Nicholas J Ashton, Andrea L Benedet, Nesrine Rahmouni, Juan Lantero-Rodriguez, Niklas Mattsson-Carlgren, Sebastian Palmqvist, Gunnar Brinkmalm, Erik Stomrud, Henrik Zetterberg, Johan Gobom, Pedro Rosa-Neto, Kaj Blennow, Oskar Hansson","doi":"10.1038/s43587-025-00951-w","DOIUrl":"https://doi.org/10.1038/s43587-025-00951-w","url":null,"abstract":"A blood biomarker-based staging system for Alzheimer's disease (AD) could improve the diagnosis, prognosis and identification of individuals most likely to benefit from specific therapies. Here, using targeted mass spectrometry, we measured six phosphorylated and six nonphosphorylated tau peptides in plasma from two independent cohorts: BioFINDER-2 and TRIAD (n = 689). We also analyzed the ratios of phosphorylated to nonphosphorylated peptides. Our results revealed that specific tau species became abnormal at different points along the disease continuum. Based on these findings, we developed a data-driven, blood-based staging model that demonstrated strong consistency across cohorts (>85% agreement in ≥90% initializations) and reflected changes in other AD biomarkers. These plasma-based stages were associated with clinical diagnoses, positron emission tomography-based stages and distinct patterns of longitudinal disease progression, including Aβ- and tau-positron emission tomography uptake, atrophy and cognitive decline. This study highlights the potential of tau blood-based biomarkers for biological staging in AD, offering a scalable tool for tracking disease progression and guiding clinical decisions.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The hidden cost of somatic mutations on skeletal muscle regeneration 体细胞突变对骨骼肌再生的隐性代价。

IF 19.4

Nature aging Pub Date : 2025-08-20 DOI: 10.1038/s43587-025-00944-9

Darren M. Blackburn, Vahab D. Soleimani

引用次数: 0

Induced somatic mutation accumulation during skeletal muscle regeneration reduces muscle strength 在骨骼肌再生过程中诱导的体细胞突变积累会降低肌肉力量。

IF 19.4

Nature aging Pub Date : 2025-08-20 DOI: 10.1038/s43587-025-00941-y

Peter Vrtačnik, Lara G. Merino, Santhilal Subhash, Hafdís T. Helgadóttir, Matthieu Bardin, Fabiana Stefani, Depin Wang, Ping Chen, Irene Franco, Gwladys Revêchon, Maria Eriksson

{"title":"Induced somatic mutation accumulation during skeletal muscle regeneration reduces muscle strength","authors":"Peter Vrtačnik, Lara G. Merino, Santhilal Subhash, Hafdís T. Helgadóttir, Matthieu Bardin, Fabiana Stefani, Depin Wang, Ping Chen, Irene Franco, Gwladys Revêchon, Maria Eriksson","doi":"10.1038/s43587-025-00941-y","DOIUrl":"10.1038/s43587-025-00941-y","url":null,"abstract":"Aging is associated with a progressive decline in tissue function and regenerative capacity, partly due to genomic instability, one of the hallmarks of aging1,2. Genomic instability encompasses DNA damage and the accumulation of somatic mutations in post-zygotic cells, yet the specific impact of these mutations on age-related tissue dysfunction remains poorly understood. To address this, we developed a mouse model in which genomic instability was induced specifically in muscle progenitor cells3 through targeted deletion of the Msh2 (ref. 4) and Blm5 genes. This allowed us to assess how elevated DNA damage and somatic mutations, from single-nucleotide variants (SNVs) to structural variants, affect muscle regeneration following injury. These mice exhibited impaired muscle regeneration, characterized by smaller muscle fibers, reduced muscle mass gain and decreased grip strength. Importantly, similar muscle deficits were observed in a second mouse model where somatic mutations were elevated with less substantial DNA damage. These findings provide evidence that the accumulation of somatic mutations can potentially compromise the function of somatic cells, contributing to the aging phenotype in skeletal muscle. With aging, somatic mutations accumulate in cellular DNA; however, whether they drive age-related functional decline is incompletely understood. Here the authors show that these mutations can weaken muscle repair and reduce strength after injury, suggesting they play a role in age-related physical decline in mouse muscle.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 9","pages":"1739-1749"},"PeriodicalIF":19.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment. 针对老年小鼠大脑中的铁相关蛋白ft1改善与年龄相关的认知障碍。

IF 19.4

Nature aging Pub Date : 2025-08-19 DOI: 10.1038/s43587-025-00940-z

Laura Remesal, Juliana Sucharov-Costa, Yuting Wu, Karishma J B Pratt, Gregor Bieri, Amber Philp, Mason Phan, Turan Aghayev, Charles W White, Elizabeth G Wheatley, Bende Zou, Brandon R Desousa, Julien Couthouis, Isha H Jian, Xinmin S Xie, Yi Lu, Jason C Maynard, Alma L Burlingame, Saul A Villeda

{"title":"Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment.","authors":"Laura Remesal, Juliana Sucharov-Costa, Yuting Wu, Karishma J B Pratt, Gregor Bieri, Amber Philp, Mason Phan, Turan Aghayev, Charles W White, Elizabeth G Wheatley, Bende Zou, Brandon R Desousa, Julien Couthouis, Isha H Jian, Xinmin S Xie, Yi Lu, Jason C Maynard, Alma L Burlingame, Saul A Villeda","doi":"10.1038/s43587-025-00940-z","DOIUrl":"10.1038/s43587-025-00940-z","url":null,"abstract":"Understanding cellular and molecular drivers of age-related cognitive decline is necessary to identify targets to restore cognition at old age. Here we identify ferritin light chain 1 (FTL1), an iron-associated protein, as a pro-aging neuronal factor that impairs cognition. Using transcriptomic and mass spectrometry approaches, we detect an increase in neuronal FTL1 in the hippocampus of aged mice, the levels of which correlate with cognitive decline. Mimicking an age-related increase in neuronal FTL1 in young mice alters labile iron oxidation states and promotes synaptic and cognitive features of hippocampal aging. Targeting neuronal FTL1 in the hippocampi of aged mice improves synaptic-related molecular changes and cognitive impairments. Using neuronal nuclei RNA sequencing, we detect changes in metabolic processes, such as ATP synthesis, and boosting these metabolic functions through NADH supplementation mitigated pro-aging effects of neuronal FTL1 on cognition. Our data identify neuronal FTL1 as a key molecular mediator of cognitive rejuvenation.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sustained immune youth risks autoimmune disease in the aging host 持续免疫的青年在衰老的宿主中有自身免疫性疾病的风险。

IF 19.4

Nature aging Pub Date : 2025-08-14 DOI: 10.1038/s43587-025-00919-w

Cornelia M. Weyand, Jörg J. Goronzy

{"title":"Sustained immune youth risks autoimmune disease in the aging host","authors":"Cornelia M. Weyand, Jörg J. Goronzy","doi":"10.1038/s43587-025-00919-w","DOIUrl":"10.1038/s43587-025-00919-w","url":null,"abstract":"Immune responses underlying autoimmune diseases follow the same principles that protect individuals from infection and malignancies. However, while protective immunity wanes with progressive age, the risk for autoimmune disease steadily increases; incidence rates for many autoimmune diseases peak in later life. Here, we discuss whether aging predisposes to autoimmunity, arguing that disease progression in the autoimmune vasculitis giant cell arteritis is driven by age-inappropriate sustenance of immune competence. Stem-like memory CD4+ T cells (TSCM) that reside near the vasculitic lesions provide a continuous supply of pathogenic effector T cells. Antigen-presenting cells lacking inhibitory ligands further impede peripheral tolerance mechanisms. In the context of aging-associated accumulation of neoantigens, this incessant immune competence sets the stage for unopposed autoimmunity. We propose that sustained immune youthfulness can be detrimental to the aging host, while immune aging may be a beneficial adaptation to balance reactivity to self-antigens and non-self-antigens and thus protect from autoimmunity in aging. Weyand and Goronzy discuss how aging increases the risk for autoimmune disease. They propose that the inappropriate endurance of immune stemness predisposes older individuals to autoimmunity, as exemplified in patients with giant cell arteritis.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1404-1414"},"PeriodicalIF":19.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immune surveillance of senescent cells in aging and disease 衰老细胞在衰老和疾病中的免疫监测。

IF 19.4

Nature aging Pub Date : 2025-08-14 DOI: 10.1038/s43587-025-00910-5

Julia Majewska, Valery Krizhanovsky

{"title":"Immune surveillance of senescent cells in aging and disease","authors":"Julia Majewska, Valery Krizhanovsky","doi":"10.1038/s43587-025-00910-5","DOIUrl":"10.1038/s43587-025-00910-5","url":null,"abstract":"Senescent cells are intrinsically immunogenic and can be eliminated by the immune system to facilitate tissue repair and regeneration. However, immune-mediated elimination is compromised with age, causing senescent cell accumulation in tissues, thus limiting healthspan and lifespan and promoting age-related diseases such as cancer. Here, we review how different components of the innate and adaptive immune systems, including natural killer cells, macrophages, neutrophils, dendritic cells, T cells and B cells, target senescent cells and how the intrinsic properties of senescent cells can lead to their escape from surveillance. We also discuss the phenomenon of senescence in immune cells themselves and how this affects the surveillance of senescent and cancerous cells. Finally, we touch on emerging therapeutic strategies to enhance the immunosurveillance of senescent cells, as understanding the molecular basis of senescence immunosurveillance and why its potency fails during aging may offer opportunities to treat senescence-mediated age-associated diseases and tissue dysfunction. Majewska and Krizhanovsky discuss the interactions of innate and adaptive immune cells with senescent cells, including mechanisms of clearance, evasion and paracrine senescence, as well as therapeutic strategies to restore surveillance in aging and disease.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1415-1424"},"PeriodicalIF":19.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic regulation of immunological aging 免疫衰老的代谢调节。

IF 19.4

Nature aging Pub Date : 2025-08-14 DOI: 10.1038/s43587-025-00921-2

Hee-Hoon Kim, Vishwa Deep Dixit

{"title":"Metabolic regulation of immunological aging","authors":"Hee-Hoon Kim, Vishwa Deep Dixit","doi":"10.1038/s43587-025-00921-2","DOIUrl":"10.1038/s43587-025-00921-2","url":null,"abstract":"All biological activities require energy through the intake and generation of metabolites. After reproductive age, altered metabolism, together with cellular and molecular perturbations in the immune system, are linked to organismal functional decline. Unresolved chronic inflammation originating from innate immune cells and loss of naive T cells with restriction of T cell receptor repertoire diversity emanating from age-related thymic involution are some of the mechanisms that limit healthspan and even lifespan. Here, we provide an overview of the hallmarks of immunological aging and synthesize how the immune system, coupled to cellular and organismal metabolism, controls disease susceptibility. Furthermore, we highlight the potential unifying immunometabolic mechanisms of various genetic, pharmacological and dietary interventions that may underlie lifespan–healthspan extension. Given that immune and metabolic systems are modifiable and targetable, understanding the role of myriads of organ-resident immune cells and the underlying metabolic mechanisms that cause dysfunction can have transformational potential for the health of older adults. Kim and Dixit review the hallmarks of immune aging with a focus on the interplay between metabolism and immune aging. They highlight metabolic pathways as potential therapeutic targets to improve immune function and organismal health in aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1425-1440"},"PeriodicalIF":19.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aging reshapes the adaptive immune system from healer to saboteur 衰老将适应性免疫系统从治疗者重塑为破坏者。

IF 19.4

Nature aging Pub Date : 2025-08-14 DOI: 10.1038/s43587-025-00906-1

Sandra Delgado-Pulido, Matthew J. Yousefzadeh, Maria Mittelbrunn

{"title":"Aging reshapes the adaptive immune system from healer to saboteur","authors":"Sandra Delgado-Pulido, Matthew J. Yousefzadeh, Maria Mittelbrunn","doi":"10.1038/s43587-025-00906-1","DOIUrl":"10.1038/s43587-025-00906-1","url":null,"abstract":"The classical role of adaptive immunity as a protector against external threats has expanded to include its functions in cancer surveillance, tissue repair and regeneration, and, more recently, it has emerged as a regulator of the aging process. In this Perspective, we discuss the mechanisms by which the deterioration of adaptive immunity contributes to inflammaging, cellular senescence and age-associated pathologies. We propose that age-related changes in lymphocytes contribute to aging through two distinct mechanisms. First, adaptive immune function worsens with age, impairing immunosurveillance of damaged or senescent cells and diminishing tissue regenerative potential, thereby indirectly disrupting tissue homeostasis. This disruption is particularly important in the gut, where maintaining tissue and microbiota homeostasis is crucial for overall health during aging. Second, adaptive immune cells often acquire pro-inflammatory and autoaggressive phenotypes with age, directly driving tissue damage, promoting senescence and exacerbating inflammaging. Finally, we explore the therapeutic potential of strategies aimed at enhancing the protective functions of lymphocytes or modulating their pathogenic phenotypes to promote healthy aging. Delgado-Pulido, Yousefzadeh and Mittelbrunn explore the molecular mechanisms by which adaptive immunity regulates the processes of aging, discussing age-related declines in protective functions and age-related gains of autoaggressive features in turn.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1393-1403"},"PeriodicalIF":19.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0