Nature aging最新文献_第5页

Activation of AMPK by GLP-1R agonists mitigates Alzheimer-related phenotypes in transgenic mice. GLP-1R激动剂激活AMPK可减轻转基因小鼠的阿尔茨海默病相关表型。

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Nature aging Pub Date : 2025-06-01 Epub Date: 2025-05-20 DOI: 10.1038/s43587-025-00869-3

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

{"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":"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.","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}

引用次数: 0

Epigenetic editing at individual age-associated CpGs affects the genome-wide epigenetic aging landscape. 个体年龄相关CpGs的表观遗传编辑影响全基因组表观遗传衰老景观。

IF 17

Nature aging Pub Date : 2025-06-01 Epub Date: 2025-03-24 DOI: 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":"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.","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}

引用次数: 0

X inactivation shows frail ends when mice age. 当小鼠衰老时，X染色体失活显示出脆弱的末端。

IF 17

Nature aging Pub Date : 2025-06-01 DOI: 10.1038/s43587-025-00874-6

Anton Wutz

引用次数: 0

Aging promotes reactivation of the Barr body at distal chromosome regions. 衰老促进远端染色体区域Barr体的再激活。

IF 17

Nature aging Pub Date : 2025-06-01 Epub Date: 2025-05-01 DOI: 10.1038/s43587-025-00856-8

Sarah Hoelzl, Tim P Hasenbein, Stefan Engelhardt, Daniel Andergassen

引用次数: 0

A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions. 基于转录组的人类普遍衰老指数（hUSI）在各种条件下可靠地预测细胞衰老。

IF 17

Nature aging Pub Date : 2025-06-01 Epub Date: 2025-05-29 DOI: 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":"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.","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}

引用次数: 0

Editing epigenetic age. 编辑表观遗传年龄。

IF 17

Nature aging Pub Date : 2025-06-01 DOI: 10.1038/s43587-025-00893-3

Bastiaan T Heijmans

引用次数: 0

Pace of Aging analysis of healthspan and lifespan in older adults in the US and UK. 美国和英国老年人健康跨度和寿命的老龄化速度分析。

IF 17

Nature aging Pub Date : 2025-06-01 Epub Date: 2025-05-26 DOI: 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":"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.","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}

引用次数: 0

GLP-1R agonists protect against Alzheimer's disease by rewiring energy regulation. GLP-1R激动剂通过重新布线能量调节来预防阿尔茨海默病。

IF 17

Nature aging Pub Date : 2025-06-01 DOI: 10.1038/s43587-025-00881-7

Daxiang Na, Marc Schneeberger Pané

引用次数: 0

Harnessing a noncanonical vestibular input in the head-direction network to rectify age-related navigational deficits. 利用头部方向网络中的非规范前庭输入来纠正与年龄相关的导航缺陷。

IF 17

Nature aging Pub Date : 2025-06-01 Epub Date: 2025-05-28 DOI: 10.1038/s43587-025-00884-4

Xiao-Qian Hu, Kenneth Lap-Kei Wu, Kang-Lin Rong, Ya Ke, Wing-Ho Yung, Daisy Kwok-Yan Shum, Ying-Shing Chan

{"title":"Harnessing a noncanonical vestibular input in the head-direction network to rectify age-related navigational deficits.","authors":"Xiao-Qian Hu, Kenneth Lap-Kei Wu, Kang-Lin Rong, Ya Ke, Wing-Ho Yung, Daisy Kwok-Yan Shum, Ying-Shing Chan","doi":"10.1038/s43587-025-00884-4","DOIUrl":"10.1038/s43587-025-00884-4","url":null,"abstract":"Navigational decline is a metric distinct from aging-related cognitive degradation, yet the affected circuits and synaptic changes remain elusive. This study identified a long-range excitatory projection from parvalbumin (PV) neurons in the brainstem medial vestibular nucleus (MVN) of mice that monosynaptically innervates the midbrain dorsal tegmental nucleus (DTN). This PVMVN→DTN projection exhibits high neuronal excitability and synaptic plasticity as electrophysiological traits. In vivo chemogenetic inhibition of the PVMVN→DTN projection impaired the navigational performance of adult mice. Navigational deficits in aged mice linked to both diminished innervation and synaptic drive of the PVMVN→DTN pathway were pinpointed as hallmarks of the aging process. Strikingly, targeted activation of this pathway mitigated navigational impairments in older mice. In sum, our results revealed an excitatory PVMVN→DTN pathway that impacts navigation. Rescue from aging-related navigational decline by activation of a spared projection pathway further highlights the potential for targeted therapies.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"1079-1096"},"PeriodicalIF":17.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176371","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

Life-course approaches are needed to foster equitable healthy aging. 需要采取生命过程方法来促进公平健康的老龄化。

IF 17

Nature aging Pub Date : 2025-06-01 DOI: 10.1038/s43587-025-00875-5

Anita van Zwieten, Suraj Samtani, Mouna Sawan, Jo-An Occhipinti, J Jaime Miranda, Saman Khalatbari-Soltani

引用次数: 0