Nature aging最新文献_第5页

The Women In Autophagy network empowers global equity in science. 自噬中的女性网络促进了科学领域的全球平等。

IF 17

Nature aging Pub Date : 2025-04-01 DOI: 10.1038/s43587-025-00839-9

Ghita Ghislat, Inmaculada Tasset

引用次数: 0

Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging. 性别特异性和细胞类型特异性变化的伴侣介导的自噬跨组织在衰老过程中。

IF 17

Nature aging Pub Date : 2025-04-01 Epub Date: 2025-02-05 DOI: 10.1038/s43587-024-00799-6

Rabia R Khawaja, Adrián Martín-Segura, Olaya Santiago-Fernández, Rebecca Sereda, Kristen Lindenau, Mericka McCabe, Adrián Macho-González, Maryam Jafari, Aurora Scrivo, Raquel Gomez-Sintes, Bhakti Chavda, Ana Rosa Saez-Ibanez, Inmaculada Tasset, Esperanza Arias, Xianhong Xie, Mimi Kim, Susmita Kaushik, Ana Maria Cuervo

{"title":"Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging.","authors":"Rabia R Khawaja, Adrián Martín-Segura, Olaya Santiago-Fernández, Rebecca Sereda, Kristen Lindenau, Mericka McCabe, Adrián Macho-González, Maryam Jafari, Aurora Scrivo, Raquel Gomez-Sintes, Bhakti Chavda, Ana Rosa Saez-Ibanez, Inmaculada Tasset, Esperanza Arias, Xianhong Xie, Mimi Kim, Susmita Kaushik, Ana Maria Cuervo","doi":"10.1038/s43587-024-00799-6","DOIUrl":"10.1038/s43587-024-00799-6","url":null,"abstract":"Aging leads to progressive decline in organ and tissue integrity and function, partly due to loss of proteostasis and autophagy malfunctioning. A decrease with age in chaperone-mediated autophagy (CMA), a selective type of lysosomal degradation, has been reported in various organs and cells from rodents and humans. Disruption of CMA recapitulates features of aging, whereas activating CMA in mice protects against age-related diseases such as Alzheimer's, retinal degeneration and/or atherosclerosis. However, sex-specific and cell-type-specific differences in CMA with aging remain unexplored. Here, using CMA reporter mice and single-cell transcriptomic data, we report that most organs and cell types show CMA decline with age, with males exhibiting a greater decline with aging. Reduced CMA is often associated with fewer lysosomes competent for CMA. Transcriptional downregulation of CMA genes may further contribute to CMA decline, especially in males. These findings suggest that CMA differences may influence organ vulnerability to age-related degeneration.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"691-708"},"PeriodicalIF":17.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257574","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

Single-cell immune aging clocks reveal inter-individual heterogeneity during infection and vaccination. 单细胞免疫老化时钟揭示了感染和接种过程中个体间的异质性。

IF 17

Nature aging Pub Date : 2025-04-01 Epub Date: 2025-03-05 DOI: 10.1038/s43587-025-00819-z

Wenchao Li, Zhenhua Zhang, Saumya Kumar, Javier Botey-Bataller, Martijn Zoodsma, Ali Ehsani, Qiuyao Zhan, Ahmed Alaswad, Liang Zhou, Inge Grondman, Valerie Koeken, Jian Yang, Gang Wang, Sonja Volland, Tania O Crişan, Leo A B Joosten, Thomas Illig, Cheng-Jian Xu, Mihai G Netea, Yang Li

{"title":"Single-cell immune aging clocks reveal inter-individual heterogeneity during infection and vaccination.","authors":"Wenchao Li, Zhenhua Zhang, Saumya Kumar, Javier Botey-Bataller, Martijn Zoodsma, Ali Ehsani, Qiuyao Zhan, Ahmed Alaswad, Liang Zhou, Inge Grondman, Valerie Koeken, Jian Yang, Gang Wang, Sonja Volland, Tania O Crişan, Leo A B Joosten, Thomas Illig, Cheng-Jian Xu, Mihai G Netea, Yang Li","doi":"10.1038/s43587-025-00819-z","DOIUrl":"10.1038/s43587-025-00819-z","url":null,"abstract":"Aging affects human immune system functionality, increasing susceptibility to immune-mediated diseases. While gene expression programs accurately reflect immune function, their relationship with biological immune aging and health status remains unclear. Here we developed robust, cell-type-specific aging clocks (sc-ImmuAging) for the myeloid and lymphoid immune cell populations in circulation within peripheral blood mononuclear cells, using single-cell RNA-sequencing data from 1,081 healthy individuals aged from 18 to 97 years. Application of sc-ImmuAging to transcriptome data of patients with COVID-19 revealed notable age acceleration in monocytes, which decreased during recovery. Furthermore, inter-individual variations in immune aging induced by vaccination were identified, with individuals exhibiting elevated baseline interferon response genes showing age rejuvenation in CD8+ T cells after BCG vaccination. sc-ImmuAging provides a powerful tool for decoding immune aging dynamics, offering insights into age-related immune alterations and potential interventions to promote healthy aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"607-621"},"PeriodicalIF":17.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569292","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

Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials. 血浆p-tau217和tau-PET预测认知功能未受损个体的未来认知能力下降：对临床试验的影响

IF 17

Nature aging Pub Date : 2025-03-28 DOI: 10.1038/s43587-025-00835-z

Rik Ossenkoppele, Gemma Salvadó, Shorena Janelidze, Alexa Pichet Binette, Divya Bali, Linda Karlsson, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Erik Stomrud, Joseph Therriault, Nesrine Rahmouni, Pedro Rosa-Neto, Emma M Coomans, Elsmarieke van de Giessen, Wiesje M van der Flier, Charlotte E Teunissen, Erin M Jonaitis, Sterling C Johnson, Sylvia Villeneuve, Tammie L S Benzinger, Suzanne E Schindler, Randall J Bateman, James D Doecke, Vincent Doré, Azadeh Feizpour, Colin L Masters, Christopher Rowe, Heather J Wiste, Ronald C Petersen, Clifford R Jack, Oskar Hansson

{"title":"Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials.","authors":"Rik Ossenkoppele, Gemma Salvadó, Shorena Janelidze, Alexa Pichet Binette, Divya Bali, Linda Karlsson, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Erik Stomrud, Joseph Therriault, Nesrine Rahmouni, Pedro Rosa-Neto, Emma M Coomans, Elsmarieke van de Giessen, Wiesje M van der Flier, Charlotte E Teunissen, Erin M Jonaitis, Sterling C Johnson, Sylvia Villeneuve, Tammie L S Benzinger, Suzanne E Schindler, Randall J Bateman, James D Doecke, Vincent Doré, Azadeh Feizpour, Colin L Masters, Christopher Rowe, Heather J Wiste, Ronald C Petersen, Clifford R Jack, Oskar Hansson","doi":"10.1038/s43587-025-00835-z","DOIUrl":"https://doi.org/10.1038/s43587-025-00835-z","url":null,"abstract":"Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma p-tau217 and medial temporal lobe tau-PET signal display similar associations with cognitive decline on a global cognitive composite test (R2PET = 0.34 versus R2plasma = 0.33, Pdifference = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR)PET = 1.61 (1.48-1.76) versus HRplasma = 1.57 (1.43-1.72), Pdifference = 0.322). Combined plasma and PET models were superior to the single-biomarker models (R2 = 0.35, P < 0.01). Sequential selection using plasma phosphorylated tau at threonine 217 (p-tau217) and then tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 76% reduction when using plasma p-tau217 alone. Thus, plasma p-tau217 and tau-PET showed similar performance for predicting future cognitive decline in CU individuals, and their sequential use enhances screening efficiency for preclinical AD trials.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743201","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 : 2025-03-24 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":"https://doi.org/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":""},"PeriodicalIF":17.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702207","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

A systematic review with a Burden of Proof meta-analysis of health effects of long-term ambient fine particulate matter (PM_2.5) exposure on dementia. 长期暴露于环境细颗粒物（PM2.5）对痴呆健康影响的系统回顾和举证责任荟萃分析。

IF 17

Nature aging Pub Date : 2025-03-21 DOI: 10.1038/s43587-025-00844-y

Xinmei Huang, Jaimie Steinmetz, Elizabeth K Marsh, Aleksandr Y Aravkin, Charlie Ashbaugh, Christopher J L Murray, Fanghan Yang, John S Ji, Peng Zheng, Reed J D Sorensen, Sarah Wozniak, Simon I Hay, Susan A McLaughlin, Vanessa Garcia, Michael Brauer, Katrin Burkart

{"title":"A systematic review with a Burden of Proof meta-analysis of health effects of long-term ambient fine particulate matter (PM2.5) exposure on dementia.","authors":"Xinmei Huang, Jaimie Steinmetz, Elizabeth K Marsh, Aleksandr Y Aravkin, Charlie Ashbaugh, Christopher J L Murray, Fanghan Yang, John S Ji, Peng Zheng, Reed J D Sorensen, Sarah Wozniak, Simon I Hay, Susan A McLaughlin, Vanessa Garcia, Michael Brauer, Katrin Burkart","doi":"10.1038/s43587-025-00844-y","DOIUrl":"10.1038/s43587-025-00844-y","url":null,"abstract":"Previous studies have indicated increased dementia risk associated with fine particulate matter (PM2.5) exposure; however, the findings are inconsistent. In this systematic review, we assessed the association between long-term PM2.5 exposure and dementia outcomes using the Burden of Proof meta-analytic framework, which relaxes log-linear assumptions to better characterize relative risk functions and quantify unexplained between-study heterogeneity (PROSPERO, ID CRD42023421869). Here we report a meta-analysis of 28 longitudinal cohort studies published up to June 2023 that investigated long-term PM2.5 exposure and dementia outcomes. We derived risk-outcome scores (ROSs), highly conservative measures of effect size and evidence strength, mapped onto a 1-5-star rating from 'weak and/or inconsistent evidence' to 'very strong and/or consistent evidence'. We identified a significant nonlinear relationship between PM2.5 exposure and dementia, with a minimum 14% increased risk averaged across PM2.5 levels between 4.5 and 26.9 µg m-3 (the 15th to 85th percentile exposure range across included studies), relative to a reference of 2.0 µg m-3 (n = 49, ROS = 0.13, two stars). We found a significant association of PM2.5 with Alzheimer's disease (n = 12, ROS = 0.32, three stars) but not with vascular dementia. Our findings highlight the potential impact of air pollution on brain aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677430","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

Palliative care use in Taiwanese older adults 台湾老年人缓和疗护之使用。

IF 17

Nature aging Pub Date : 2025-03-11 DOI: 10.1038/s43587-025-00843-z

Anna Kriebs

引用次数: 0

Exposing the exposome in aging 在衰老中暴露暴露者。

IF 17

Nature aging Pub Date : 2025-03-11 DOI: 10.1038/s43587-025-00845-x

George Andrew S. Inglis

引用次数: 0

Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease 亚细胞蛋白质组学和iPSC模型揭示了阿尔茨海默病轴突病理的可逆机制。

IF 17

Nature aging Pub Date : 2025-03-10 DOI: 10.1038/s43587-025-00823-3

Yifei Cai, Jean Kanyo, Rashaun Wilson, Shveta Bathla, Pablo Leal Cardozo, Lei Tong, Shanshan Qin, Lukas A. Fuentes, Iguaracy Pinheiro-de-Sousa, Tram Huynh, Liyuan Sun, Mohammad Shahid Mansuri, Zichen Tian, Hao-Ran Gan, Amber Braker, Hoang Kim Trinh, Anita Huttner, TuKiet T. Lam, Evangelia Petsalaki, Kristen J. Brennand, Angus C. Nairn, Jaime Grutzendler

{"title":"Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease","authors":"Yifei Cai, Jean Kanyo, Rashaun Wilson, Shveta Bathla, Pablo Leal Cardozo, Lei Tong, Shanshan Qin, Lukas A. Fuentes, Iguaracy Pinheiro-de-Sousa, Tram Huynh, Liyuan Sun, Mohammad Shahid Mansuri, Zichen Tian, Hao-Ran Gan, Amber Braker, Hoang Kim Trinh, Anita Huttner, TuKiet T. Lam, Evangelia Petsalaki, Kristen J. Brennand, Angus C. Nairn, Jaime Grutzendler","doi":"10.1038/s43587-025-00823-3","DOIUrl":"10.1038/s43587-025-00823-3","url":null,"abstract":"Dystrophic neurites (also termed axonal spheroids) are found around amyloid deposits in Alzheimer’s disease (AD), where they impair axonal electrical conduction, disrupt neural circuits and correlate with AD severity. Despite their importance, the mechanisms underlying spheroid formation remain incompletely understood. To address this, we developed a proximity labeling approach to uncover the proteome of spheroids in human postmortem and mouse brains. Additionally, we established a human induced pluripotent stem cell (iPSC)-derived AD model enabling mechanistic investigation and optical electrophysiology. These complementary approaches revealed the subcellular molecular architecture of spheroids and identified abnormalities in key biological processes, including protein turnover, cytoskeleton dynamics and lipid transport. Notably, the PI3K/AKT/mTOR pathway, which regulates these processes, was activated in spheroids. Furthermore, phosphorylated mTOR levels in spheroids correlated with AD severity in humans. Notably, mTOR inhibition in iPSC-derived neurons and mice ameliorated spheroid pathology. Altogether, our study provides a multidisciplinary toolkit for investigating mechanisms and therapeutic targets for axonal pathology in neurodegeneration. Axonal spheroids disrupt neural circuits in Alzheimer’s disease. In this study, using subcellular proximity labeling proteomics in human brain and iPSC modeling, the authors link spheroid formation to dysregulated mTOR, cytoskeletal and lipid transport signaling.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 3","pages":"504-527"},"PeriodicalIF":17.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-025-00823-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598671","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

A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan 小鼠的类似冬眠状态减缓了血液表观遗传老化，延长了健康寿命。

IF 17

Nature aging Pub Date : 2025-03-07 DOI: 10.1038/s43587-025-00830-4

Lorna Jayne, Aurora Lavin-Peter, Julian Roessler, Alexander Tyshkovskiy, Mateusz Antoszewski, Erika Ren, Aleksandar Markovski, Senmiao Sun, Hanqi Yao, Vijay G. Sankaran, Vadim N. Gladyshev, Robert T. Brooke, Steve Horvath, Eric C. Griffith, Sinisa Hrvatin

{"title":"A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan","authors":"Lorna Jayne, Aurora Lavin-Peter, Julian Roessler, Alexander Tyshkovskiy, Mateusz Antoszewski, Erika Ren, Aleksandar Markovski, Senmiao Sun, Hanqi Yao, Vijay G. Sankaran, Vadim N. Gladyshev, Robert T. Brooke, Steve Horvath, Eric C. Griffith, Sinisa Hrvatin","doi":"10.1038/s43587-025-00830-4","DOIUrl":"10.1038/s43587-025-00830-4","url":null,"abstract":"Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase healthspan, remain unknown. Here we demonstrate that the activity of a spatially defined neuronal population in the preoptic area, which has previously been identified as a torpor-regulating brain region, is sufficient to induce a torpor-like state (TLS) in mice. Prolonged induction of TLS slows epigenetic aging across multiple tissues and improves healthspan. We isolate the effects of decreased metabolic rate, long-term caloric restriction, and decreased core body temperature (Tb) on blood epigenetic aging and find that the decelerating effect of TLSs on aging is mediated by decreased Tb. Taken together, our findings provide novel mechanistic insight into the decelerating effects of torpor and hibernation on aging and support the growing body of evidence that Tb is an important mediator of the aging processes. Dissecting the effects of hypothermic and hypometabolic states on aging processes, the authors show that activation of neurons in the preoptic area induces a torpor-like state in mice that slows epigenetic aging and improves healthspan. These pro-longevity effects are mediated by reduced Tb, reinforcing evidence that Tb is a key mediator of aging processes.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 3","pages":"437-449"},"PeriodicalIF":17.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-025-00830-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588906","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