Nature aging最新文献_第6页

Understanding and improving vaccine efficacy in older adults 了解和提高疫苗在老年人中的效力。

IF 19.4

Nature aging Pub Date : 2025-08-14 DOI: 10.1038/s43587-025-00939-6

Sebastian J. Hofer, Simon Rapp, Paul Klenerman, Anna Katharina Simon

{"title":"Understanding and improving vaccine efficacy in older adults","authors":"Sebastian J. Hofer, Simon Rapp, Paul Klenerman, Anna Katharina Simon","doi":"10.1038/s43587-025-00939-6","DOIUrl":"10.1038/s43587-025-00939-6","url":null,"abstract":"Cellular aging of the immune system, commonly referred to as ‘immunosenescence’, drives a substantial decline in vaccine efficacy among older adults, who are already typically at a higher risk of reduced infection control. Therefore, preventive medicine requires novel strategies to improve vaccination in older adults, particularly by finding ways to mitigate immunosenescence and chronic inflammation. Here, we review how technical innovations, such as increased antigen amounts, improved adjuvants and mRNA-based and universal vaccines, can complement traditional methods of improving vaccination success in older adults. Furthermore, we discuss emerging clinical evidence suggesting that geroscience interventions, such as mTOR inhibition and caloric restriction, can enhance vaccine outcomes in older adults, potentially by targeting molecular aspects of immunosenescence and systemic characteristics of aging, including metabolic changes in the blood and chronic inflammation. Ultimately, we propose that integrating geroscience with tailored immunization could attenuate the effects of immune aging on vaccination efficacy in older populations. Hofer and colleagues explore how immunosenescence impairs vaccine efficacy in older adults, then review emerging vaccine technologies and gerotherapeutic interventions as strategies to enhance protective responses.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1455-1470"},"PeriodicalIF":19.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857303","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 immune system offers a window into aging 免疫系统为衰老提供了一个窗口。

IF 19.4

Nature aging Pub Date : 2025-08-14 DOI: 10.1038/s43587-025-00948-5

引用次数: 0

Restoring resident tissue macrophages to combat aging and cancer 恢复常驻组织巨噬细胞对抗衰老和癌症。

IF 19.4

Nature aging Pub Date : 2025-08-14 DOI: 10.1038/s43587-025-00898-y

Matthew D. Park, Nader Yatim, Jing Zhang, Byuri Angela Cho, Seong-Keun Yoo, Maximilian M. Schaefer, Diego Chowell, Daniel J. Puleston, Miriam Merad

{"title":"Restoring resident tissue macrophages to combat aging and cancer","authors":"Matthew D. Park, Nader Yatim, Jing Zhang, Byuri Angela Cho, Seong-Keun Yoo, Maximilian M. Schaefer, Diego Chowell, Daniel J. Puleston, Miriam Merad","doi":"10.1038/s43587-025-00898-y","DOIUrl":"10.1038/s43587-025-00898-y","url":null,"abstract":"Perturbations to the immune system influence organismal aging, yet identifying effective therapeutic targets that mitigate aging-related tissue decline or the pathogenesis of aging-related diseases, such as cancer, remains challenging. In this Perspective, we focus on the dysfunction and loss of resident tissue macrophages (RTMs) with aging of certain tissues, which promote local inflammation, compromise tissue health and contribute to tumorigenesis. The abnormal genesis of RTMs from the bone marrow is a defining hallmark of both healthy and unhealthy aging. So, we propose that restoring RTMs—either by reshaping their niche and rescuing local self-renewal or by rejuvenating aging-associated myelopoiesis in the bone marrow—should be a major objective of interventions to promote healthy aging. We summarize the body of work supporting this conceptual framework and outline key future directions for the development of versatile myeloid-targeting therapies. Park and colleagues propose a conceptual framework in which dysregulation of resident tissue macrophages is both a central contributor to how an aging immune system causes diseases, including cancer, and a potential therapeutic target.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1383-1392"},"PeriodicalIF":19.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857299","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

Toward precision interventions and metrics of inflammaging 对炎症的精确干预和度量。

IF 19.4

Nature aging Pub Date : 2025-08-14 DOI: 10.1038/s43587-025-00938-7

Claudio Franceschi, Fabiola Olivieri, Alexey Moskalev, Mikhail Ivanchenko, Aurelia Santoro

{"title":"Toward precision interventions and metrics of inflammaging","authors":"Claudio Franceschi, Fabiola Olivieri, Alexey Moskalev, Mikhail Ivanchenko, Aurelia Santoro","doi":"10.1038/s43587-025-00938-7","DOIUrl":"10.1038/s43587-025-00938-7","url":null,"abstract":"Inflammaging describes a chronic, systemic, low-grade inflammatory state that is recognized as a major risk factor for age-related diseases (ARDs) and a pivotal convergence point of multiple biological mechanisms involved in aging. Here, we discuss the heterogeneity of inflammaging, proposing that it emerges as a consequence of each individual’s lifelong exposures to inflammatory stimuli, shaped by a unique combination of genetics, lifestyle, socioeconomic conditions and environmental factors such as infections and pollution. Through this lens, we then discuss measuring inflammaging, describing the development of inflammatory clocks that quantify inflammatory age and show strong associations with ARD incidence as well as how other aging clocks intersect with inflammaging. Finally, we consider interventions that may counteract inflammaging, including nutritional interventions, physical activity and gerotherapies such as senolytics. We propose that deepening our knowledge of the individual nature of inflammaging stands to enhance our understanding of personalized aging trajectories and inform precision interventions. Inflammaging is a chronic, low-grade inflammatory state that is closely linked to aging; yet it is highly heterogeneous. Within the framework of personalized medicine, Franceschi and colleagues discuss measuring and treating inflammaging, highlighting the need for precision interventions.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1441-1454"},"PeriodicalIF":19.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857302","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

Sarcosine shows promise in preventing sarcopenia 肌氨酸在预防肌肉减少症方面显示出希望。

IF 19.4

Nature aging Pub Date : 2025-08-08 DOI: 10.1038/s43587-025-00954-7

引用次数: 0

Author Correction: ImAge quantitates aging and rejuvenation 作者更正：图像量化衰老和年轻化。

IF 19.4

Nature aging Pub Date : 2025-08-05 DOI: 10.1038/s43587-025-00949-4

Martin Alvarez-Kuglen, Kenta Ninomiya, Haodong Qin, Delany Rodriguez, Lorenzo Fiengo, Chen Farhy, Wei-Mien Hsu, Brian Kirk, Aaron Havas, Collin Kaufman, Gen-Sheng Feng, Amanda J. Roberts, Rozalyn M. Anderson, Manuel Serrano, Peter D. Adams, Tatyana O. Sharpee, Alexey V. Terskikh

引用次数: 0

Large-scale genome-wide analyses with proteomics integration reveal novel loci and biological insights into frailty 大规模全基因组分析与蛋白质组学整合揭示新的位点和生物学见解脆弱。

IF 19.4

Nature aging Pub Date : 2025-08-05 DOI: 10.1038/s43587-025-00925-y

Jonathan K. L. Mak, Chenxi Qin, Moritz Krüger, Anna Kuukka, FinnGen, Sara Hägg, Jake Lin, Juulia Jylhävä

{"title":"Large-scale genome-wide analyses with proteomics integration reveal novel loci and biological insights into frailty","authors":"Jonathan K. L. Mak, Chenxi Qin, Moritz Krüger, Anna Kuukka, FinnGen, Sara Hägg, Jake Lin, Juulia Jylhävä","doi":"10.1038/s43587-025-00925-y","DOIUrl":"10.1038/s43587-025-00925-y","url":null,"abstract":"Frailty is a clinically relevant phenotype with notable gaps in our understanding of its etiology. Using the Hospital Frailty Risk Score (HFRS) to define frailty, we performed a genome-wide association study in FinnGen (N = 500,737), replicated the results in the UK Biobank (N = 407,463) and performed a meta-analysis. We prioritized genes through colocalization with expression, splicing and protein quantitative trait loci and proteomics integration. We identified 53 independent lead variants associated with frailty (P < 5 × 10−8), of which 45 were novel and not previously reported in the GWAS Catalog. Replication at the individual variant and polygenic risk score of the HFRS (P = 1.86 × 10−522) levels and meta-analysis largely confirmed the findings. Colocalization analysis supported a causal role for several genes, including CHST9, C6orf106 (ILRUN), KHK, MET, APOE, CGREF1 and PPP6C. Additionally, plasma levels of MET, CGREF1 and APOE were associated with HFRS. Our results reveal new genetic contributions to frailty and shed light on its biological basis. To better understand the etiology of frailty, the authors perform a large genetic study. They identified 45 additional variants and implicated MET, CHST9, ILRUN, APOE, CGREF1 and PPP6C as potential causal genes, linking frailty to immune regulation, metabolism and cellular signaling.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1589-1600"},"PeriodicalIF":19.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791062","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

Refining the generation, interpretation and application of multi-organ, multi-omics biological aging clocks 完善多器官、多组学生物衰老时钟的生成、解释和应用。

IF 19.4

Nature aging Pub Date : 2025-08-05 DOI: 10.1038/s43587-025-00928-9

Junhao Wen

{"title":"Refining the generation, interpretation and application of multi-organ, multi-omics biological aging clocks","authors":"Junhao Wen","doi":"10.1038/s43587-025-00928-9","DOIUrl":"10.1038/s43587-025-00928-9","url":null,"abstract":"Multi-organ biological aging clocks derived from clinical phenotypes and neuroimaging data have emerged as valuable tools for studying human aging and disease. Plasma proteomics provides an additional molecular dimension to enrich these clocks. In this study, I developed 11 multi-organ proteome-based biological age gaps (ProtBAGs) using 2,448 plasma proteins from 43,498 participants in the UK Biobank. Here I highlight methodological and clinical considerations for developing and using these clocks, including correction for age bias, organ specificity of proteins, sample size and underlying pathologies in the training data, which can affect model generalizability and clinical interpretability. In addition, I integrated 11 ProtBAGs with previously developed nine multi-organ phenotype-based biological age gaps to investigate genetic overlap and causal associations with disease endpoints. Finally, I show that incorporating features across organs improves predictions for systemic disease categories and all-cause mortality. These analyses provide methodological and clinical insights for developing and interpreting these clocks and highlight future avenues toward a multi-organ, multi-omics biological aging clock framework. In developing multi-organ-based and multi-omics-based biological aging clocks and linking them to underlying genetics and clinical phenotypes, Wen demonstrates the value of methodological and clinical considerations for enhancing model generalizability and clinical interpretability.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 9","pages":"1897-1913"},"PeriodicalIF":19.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791063","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

Stress granule clearance mediated by V-ATPase-interacting protein NCOA7 mitigates ovarian aging v - atp酶相互作用蛋白NCOA7介导的应激颗粒清除可减轻卵巢衰老。

IF 19.4

Nature aging Pub Date : 2025-07-31 DOI: 10.1038/s43587-025-00927-w

Ting Dong, Nianyu Li, Huirui Wang, Hanbing Zhu, Yinghui Gao, Yue Liu, Fang Fang, Xiaojie Fu, Pinxin Si, Cheng Li, Mei Li, Fei Wang, Shidou Zhao, Ting Guo, Linlin Cui, Xinyi Jiang, Xiaohui Liu, Han Zhao, Yingying Qin, Zi-Jiang Chen, Hongxiang Lou, Xue Jiao

{"title":"Stress granule clearance mediated by V-ATPase-interacting protein NCOA7 mitigates ovarian aging","authors":"Ting Dong, Nianyu Li, Huirui Wang, Hanbing Zhu, Yinghui Gao, Yue Liu, Fang Fang, Xiaojie Fu, Pinxin Si, Cheng Li, Mei Li, Fei Wang, Shidou Zhao, Ting Guo, Linlin Cui, Xinyi Jiang, Xiaohui Liu, Han Zhao, Yingying Qin, Zi-Jiang Chen, Hongxiang Lou, Xue Jiao","doi":"10.1038/s43587-025-00927-w","DOIUrl":"10.1038/s43587-025-00927-w","url":null,"abstract":"Reproductive longevity is essential for female fertility and healthy aging; however, the role of stress response, especially stress granule accumulation, in ovarian aging remains elusive and interventions are lacking. Here, we identified deleterious mutations and decreased expression of NCOA7, a stress-response protein related to granulosa cell senescence in women with physiological and pathological ovarian aging. NCOA7 deletion accelerates oxidative stress-related cellular senescence, ovarian aging and fecundity decline in mice. Mechanistically, NCOA7 partitions into the stress granule containing G3BP1–V-ATPase and facilitates autophagic degradation of stress granules to relieve stress. Boosting granulophagy with rapamycin or lipid nanoparticle-based mRNA delivery of NCOA7 accelerates stress granule clearance, alleviating cellular senescence in human granulosa cells and delaying ovarian aging in mice. This study depicts a mechanism for ovarian resilience to stress and provides potential targets for therapeutic strategies to alleviate ovarian aging. The role of cellular stress responses in ovarian aging remains incompletely understood. In this study, the authors identify NCOA7 as a facilitator of autophagic clearance of stress granules in granulosa cells, conveying protection against ovarian aging. Loss of NCOA7 promotes ovarian aging, whereas its expression via mRNA delivery delays aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1548-1567"},"PeriodicalIF":19.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762885","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

Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis 骨髓脂肪细胞分泌的血清淀粉样蛋白P驱动骨骼淀粉样变性。

IF 19.4

Nature aging Pub Date : 2025-07-29 DOI: 10.1038/s43587-025-00924-z

Surendra Kumar, Kangping Song, Jiekang Wang, Meghraj Singh Baghel, Yixiang Zeng, Ke Shen, Junying Zheng, Janet Crane, Shadpour Demehri, Peisong Gao, Amit Jain, Richard L. Skolasky, Philip Wong, Xu Cao, Mei Wan

{"title":"Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis","authors":"Surendra Kumar, Kangping Song, Jiekang Wang, Meghraj Singh Baghel, Yixiang Zeng, Ke Shen, Junying Zheng, Janet Crane, Shadpour Demehri, Peisong Gao, Amit Jain, Richard L. Skolasky, Philip Wong, Xu Cao, Mei Wan","doi":"10.1038/s43587-025-00924-z","DOIUrl":"10.1038/s43587-025-00924-z","url":null,"abstract":"The accumulation of amyloid fibrils has been identified in tissues outside the brain, yet little is understood about the formation of extracerebral amyloidosis and its impact on organ aging. Here, we demonstrate that both transgenic Alzheimer’s disease (AD) mice and naturally aging mice exhibit accumulated senescent bone marrow adipocytes (BMAds), accompanied by amyloid deposits. Senescent BMAds acquire a secretory phenotype, markedly increasing secretion of serum amyloid P component (SAP), also known as pentraxin 2 (PTX2). SAP/PTX2 colocalizes with amyloid deposits around senescent BMAds in vivo and promotes insoluble amyloid formation from soluble amyloid-β (Aβ) peptides in in vitro and ex vivo three-dimensional (3D) BMAd-based cultures. Combined SAP/PTX2 and Aβ treatment promotes osteoclastogenesis but inhibits osteoblastogenesis. Transplanting senescent BMAds into the bone marrow cavity of young mice induces bone loss, which is reversed by senolytic treatment. Finally, depleting SAP/PTX2 in aged mice abolishes marrow amyloid deposition and rescues low bone mass. Thus, senescent BMAds drive age-related skeletal amyloidosis and bone deficits via SAP/PTX2. Amyloid fibrils can accumulate in tissues outside the brain, yet the impact is incompletely understood. Here the researchers show that, with age, mouse bone marrow fat cells become senescent and secrete SAP/PTX2, driving amyloid buildup and bone loss. Clearing senescent fat cells or depleting SAP/PTX2 reduces marrow amyloid deposits and restores bone health.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 9","pages":"1771-1789"},"PeriodicalIF":19.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746667","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