Nature agingPub Date : 2025-06-01DOI: 10.1038/s43587-025-00905-2
George Andrew S Inglis
{"title":"Mid-life adipogenesis.","authors":"George Andrew S Inglis","doi":"10.1038/s43587-025-00905-2","DOIUrl":"10.1038/s43587-025-00905-2","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"956"},"PeriodicalIF":17.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183115","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}
Nature agingPub Date : 2025-06-01DOI: 10.1038/s43587-025-00903-4
{"title":"Pace of aging matters for healthspan and lifespan in older adults.","authors":"","doi":"10.1038/s43587-025-00903-4","DOIUrl":"10.1038/s43587-025-00903-4","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"964-965"},"PeriodicalIF":17.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188741","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}
{"title":"Activation of AMPK by GLP-1R agonists mitigates Alzheimer-related phenotypes in transgenic mice.","authors":"Yun Zhang, Huaqiu Chen, Yijia Feng, Mingjing Liu, Zhi Lu, Bolang Hu, Lifen Chen, Yang Zhang, Jiawen Liu, Fang Cai, Yifan Zhao, Wenhao Pan, Xinxin Liao, Sipei Pan, Isabel Bestard-Lorigados, Yili Wu, Weihong Song","doi":"10.1038/s43587-025-00869-3","DOIUrl":"10.1038/s43587-025-00869-3","url":null,"abstract":"<p><p>Individuals with type 2 diabetes mellitus have an increased risk of developing Alzheimer's disease (AD). GLP-1 receptor agonists (GLP-1RAs) are used for glycemic control in diabetes and show potential neuroprotective properties, but their effects on AD and the underlying mechanisms are not well understood. Here we demonstrate that GLP-1RAs can alleviate AD-related phenotypes by activating 5' AMP-activated protein kinase (AMPK) signaling. We found that plasma GLP-1 levels were decreased in AD model mice and negatively correlated with amyloid-beta (Aβ) load in patients with AD. Enhancing GLP-1 signaling through GLP-1RAs increased CaMKK2-AMPK signaling, which subsequently reduced BACE1-mediated cleavage of amyloid precursor protein (APP) and Aβ generation. GLP-1RAs also increased AMPK activity in microglia, inhibiting neuroinflammation and promoting Aβ phagocytosis. Consequently, GLP-1RAs inhibited plaque formation and improved memory deficits in AD model mice. Our findings indicate that AMPK activation mediates the effects of GLP-1RAs on AD, highlighting the therapeutic potential of GLP-1RAs for the treatment of AD.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"1097-1113"},"PeriodicalIF":17.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112916","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}
Nature agingPub Date : 2025-06-01Epub Date: 2025-03-24DOI: 10.1038/s43587-025-00841-1
Sven Liesenfelder, Mohamed H Elsafi Mabrouk, Jessica Iliescu, Monica Varona Baranda, Athanasia Mizi, Juan-Felipe Perez-Correa, Martina Wessiepe, Argyris Papantonis, Wolfgang Wagner
{"title":"Epigenetic editing at individual age-associated CpGs affects the genome-wide epigenetic aging landscape.","authors":"Sven Liesenfelder, Mohamed H Elsafi Mabrouk, Jessica Iliescu, Monica Varona Baranda, Athanasia Mizi, Juan-Felipe Perez-Correa, Martina Wessiepe, Argyris Papantonis, Wolfgang Wagner","doi":"10.1038/s43587-025-00841-1","DOIUrl":"10.1038/s43587-025-00841-1","url":null,"abstract":"<p><p>Aging is reflected by genome-wide DNA methylation changes, which form the basis of epigenetic clocks, but it is largely unclear how these epigenetic modifications are regulated and whether they directly affect the aging process. In this study, we performed epigenetic editing at age-associated CpG sites to explore the consequences of interfering with epigenetic clocks. CRISPR-guided editing targeted at individual age-related CpGs evoked genome-wide bystander effects, which were highly reproducible and enriched at other age-associated regions. 4C-sequencing at age-associated sites revealed increased interactions with bystander modifications and other age-related CpGs. Subsequently, we multiplexed epigenetic editing in human T cells and mesenchymal stromal cells at five genomic regions that become either hypermethylated or hypomethylated upon aging. While targeted methylation seemed more stable at age-hypermethylated sites, both approaches induced bystander modifications at CpGs with the highest correlations with chronological age. Notably, these effects were simultaneously observed at CpGs that gain and lose methylation with age. Our results demonstrate that epigenetic editing can extensively modulate the epigenetic aging network and interfere with epigenetic clocks.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"997-1009"},"PeriodicalIF":17.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702207","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}
Nature agingPub Date : 2025-06-01Epub Date: 2025-05-01DOI: 10.1038/s43587-025-00856-8
Sarah Hoelzl, Tim P Hasenbein, Stefan Engelhardt, Daniel Andergassen
{"title":"Aging promotes reactivation of the Barr body at distal chromosome regions.","authors":"Sarah Hoelzl, Tim P Hasenbein, Stefan Engelhardt, Daniel Andergassen","doi":"10.1038/s43587-025-00856-8","DOIUrl":"10.1038/s43587-025-00856-8","url":null,"abstract":"<p><p>Decades ago, evidence of age-related reactivation of a single gene on the female inactive X chromosome was observed in mice. While stable silencing of the Barr body is crucial for balancing gene dosage between sexes, it remains unclear whether silencing is maintained during aging. Here we used allele-specific multi-omics approaches to capture a comprehensive catalog of genes escaping X chromosome inactivation throughout mouse development and aging. We found substantially elevated escape rates during aging across organs, occurring in multiple distinct cell types and concentrated at distal chromosome regions. Consistently, chromatin accessibility was increased across multiple megabases at chromosome ends, affecting regulatory elements of escapees. As several age-specific escapees are linked to human diseases, their elevated expression in females might contribute to sex-biased disease progression observed during aging.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"984-996"},"PeriodicalIF":17.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015519","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}
Nature agingPub Date : 2025-06-01Epub Date: 2025-05-29DOI: 10.1038/s43587-025-00886-2
Jing Wang, Xiaolan Zhou, Peng Yu, Jun Yao, Pengfei Guo, Qiushi Xu, Yuqi Zhao, Guanlong Wang, Qianru Li, Xiaofeng Zhu, Gang Wei, Weixu Wang, Ting Ni
{"title":"A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions.","authors":"Jing Wang, Xiaolan Zhou, Peng Yu, Jun Yao, Pengfei Guo, Qiushi Xu, Yuqi Zhao, Guanlong Wang, Qianru Li, Xiaofeng Zhu, Gang Wei, Weixu Wang, Ting Ni","doi":"10.1038/s43587-025-00886-2","DOIUrl":"10.1038/s43587-025-00886-2","url":null,"abstract":"<p><p>Despite the manifestation and contribution of cellular senescence to aging and various diseases, accurate identification of heterogeneous senescent cells remains challenging. Current senescence evaluation methods rely mainly on limited markers or homogeneous samples, which might fail to capture universal senescence features, limiting their generalizability. Here we developed the human universal senescence index (hUSI), an accurate and robust senescence evaluation method for diverse cells and samples. Based on features learned from the most comprehensive cellular senescence-associated transcriptome data so far, hUSI demonstrated its convincing connections with senescence phenotypes and superior robustness in predicting senescence state. Using hUSI, we discovered potential senescence regulators and mapped senescent cell accumulation across cell types in coronavirus disease 2019 (COVID-19). The method also facilitates decoding heterogeneous senescence states in melanoma tumors, identifying prognosis-associated signaling pathways. Overall, hUSI demonstrates its utility in characterizing cellular senescence across biological contexts, with broad applications in aging research and clinical practice.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"1159-1175"},"PeriodicalIF":17.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182703","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}
Nature agingPub Date : 2025-06-01Epub Date: 2025-05-26DOI: 10.1038/s43587-025-00866-6
Arun Balachandran, Heming Pei, Yifan Shi, John R Beard, Avshalom Caspi, Alan A Cohen, Benjamin W Domingue, Claire Eckstein Indik, Luigi Ferrucci, Alex Furuya, Meeraj Kothari, Terrie E Moffitt, Calen P Ryan, Vegard Skirbekk, Yuan S Zhang, Daniel W Belsky
{"title":"Pace of Aging analysis of healthspan and lifespan in older adults in the US and UK.","authors":"Arun Balachandran, Heming Pei, Yifan Shi, John R Beard, Avshalom Caspi, Alan A Cohen, Benjamin W Domingue, Claire Eckstein Indik, Luigi Ferrucci, Alex Furuya, Meeraj Kothari, Terrie E Moffitt, Calen P Ryan, Vegard Skirbekk, Yuan S Zhang, Daniel W Belsky","doi":"10.1038/s43587-025-00866-6","DOIUrl":"10.1038/s43587-025-00866-6","url":null,"abstract":"<p><p>As societies age, policy makers need tools to understand how demographic aging will affect population health and to develop programs to increase healthspan. The current metrics used for policy do not distinguish differences caused by early-life factors, like prenatal care and nutrition, from those caused by ongoing changes in people's bodies that are due to aging and that may be modifiable. Here we introduce an adapted Pace of Aging method designed to quantify differences between individuals and populations in the speed of aging-related health declines. The adapted Pace of Aging method, implemented in parallel in data from the US Health and Retirement Study and in the English Longitudinal Study of Aging (combined n = 19,045), integrates longitudinal data on blood biomarkers, physical measurements and functional tests. It reveals stark differences in rates of aging between population subgroups and demonstrates strong and consistent prospective associations with incident morbidity, disability and mortality. This adapted and generalizable method to measure Pace of Aging can advance the population science of healthy longevity.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"1132-1142"},"PeriodicalIF":17.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153149","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}
Nature agingPub Date : 2025-06-01DOI: 10.1038/s43587-025-00881-7
Daxiang Na, Marc Schneeberger Pané
{"title":"GLP-1R agonists protect against Alzheimer's disease by rewiring energy regulation.","authors":"Daxiang Na, Marc Schneeberger Pané","doi":"10.1038/s43587-025-00881-7","DOIUrl":"10.1038/s43587-025-00881-7","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"960-961"},"PeriodicalIF":17.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112977","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}