Nature aging最新文献

Regeneration leads to global tissue rejuvenation in aging sexual planarians.

IF 17

Nature aging Pub Date : 2025-04-03 DOI: 10.1038/s43587-025-00847-9

Xiaoting Dai, Xinghua Li, Alexander Tyshkovskiy, Cassandra Zuckerman, Nan Cheng, Peter Lin, David Paris, Saad Qureshi, Leonid Kruglyak, Xiaoming Mao, Jayakrishnan Nandakumar, Vadim N Gladyshev, Scott Pletcher, Jacob Sobota, Longhua Guo

{"title":"Regeneration leads to global tissue rejuvenation in aging sexual planarians.","authors":"Xiaoting Dai, Xinghua Li, Alexander Tyshkovskiy, Cassandra Zuckerman, Nan Cheng, Peter Lin, David Paris, Saad Qureshi, Leonid Kruglyak, Xiaoming Mao, Jayakrishnan Nandakumar, Vadim N Gladyshev, Scott Pletcher, Jacob Sobota, Longhua Guo","doi":"10.1038/s43587-025-00847-9","DOIUrl":"https://doi.org/10.1038/s43587-025-00847-9","url":null,"abstract":"The possibility of reversing the adverse impacts of aging could significantly reduce age-related diseases and improve quality of life in older populations. Here we report that the sexual lineage of the planarian Schmidtea mediterranea exhibits physiological decline within 18 months of birth, including altered tissue architecture, impaired fertility and motility, and increased oxidative stress. Single-cell profiling of young and older planarian heads uncovered loss of neurons and muscle, increase of glia, and revealed minimal changes in somatic pluripotent stem cells, along with molecular signatures of aging across tissues. Remarkably, amputation followed by regeneration of lost tissues in older planarians led to reversal of these age-associated changes in tissues both proximal and distal to the injury at physiological, cellular and molecular levels. Our work suggests mechanisms of rejuvenation in both new and old tissues concurring with planarian regeneration, which may provide valuable insights for antiaging interventions.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782202","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 advantages and challenges of disability-free survival as outcome measure in clinical studies.

IF 17

Nature aging Pub Date : 2025-04-01 DOI: 10.1038/s43587-025-00853-x

Johannes T Neumann, John J McNeil

引用次数: 0

Pathways that limit differentiation of oligodendrocyte progenitors in the aging brain. 限制衰老大脑少突胶质细胞祖细胞分化的途径

IF 17

Nature aging Pub Date : 2025-04-01 DOI: 10.1038/s43587-025-00848-8

引用次数: 0

Transcriptional profiles of mouse oligodendrocyte precursor cells across the lifespan.

IF 17

Nature aging Pub Date : 2025-03-31 DOI: 10.1038/s43587-025-00840-2

Dongeun Heo, Anya A Kim, Björn Neumann, Valerie N Doze, Yu Kang T Xu, Yevgeniya A Mironova, Jared Slosberg, Loyal A Goff, Robin J M Franklin, Dwight E Bergles

{"title":"Transcriptional profiles of mouse oligodendrocyte precursor cells across the lifespan.","authors":"Dongeun Heo, Anya A Kim, Björn Neumann, Valerie N Doze, Yu Kang T Xu, Yevgeniya A Mironova, Jared Slosberg, Loyal A Goff, Robin J M Franklin, Dwight E Bergles","doi":"10.1038/s43587-025-00840-2","DOIUrl":"10.1038/s43587-025-00840-2","url":null,"abstract":"Oligodendrocyte progenitor cells (OPCs) are highly dynamic, widely distributed glial cells of the central nervous system responsible for generating myelinating oligodendrocytes throughout life. However, the rates of OPC proliferation and differentiation decline dramatically with aging, which may impair homeostasis, remyelination and adaptive myelination during learning. To determine how aging influences OPCs, we generated a transgenic mouse line (Matn4-mEGFP) and performed single-cell RNA sequencing, providing enhanced resolution of transcriptional changes during key transitions from quiescence to proliferation and differentiation across the lifespan. We found that aging induces distinct transcriptomic changes in OPCs in different states, including enhanced activation of HIF-1α and WNT pathways. Pharmacological inhibition of these pathways in aged OPCs was sufficient to increase their ability to differentiate in vitro. Ultimately, Matn4-mEGFP mouse line and the sequencing dataset of cortical OPCs across ages will help to define the molecular changes guiding OPC behavior in various physiological and pathological contexts.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756955","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

Invigorating discovery and clinical translation of aging biomarkers.

IF 17

Nature aging Pub Date : 2025-03-31 DOI: 10.1038/s43587-025-00838-w

Erik Jacques, Chiara Herzog, Kejun Ying, Alan Tomusiak, Jessica Kasamoto, Raghav Sehgal, Seth Paulson, Julian Reinhard, Jakob Träuble, Waylon J Hastings, Alexander Tyshkovskiy, Sara Hägg, John C Earls, Christian E Behrens, Jessica Lasky-Su, Gavin Zhou, Eric Morgen, John S Tsang, Riccardo E Marioni, Xiao-Jun Ma, Alexandra Stolzing, Christin Glorioso, Jonathan S Gootenberg, Omar O Abudayyeh, M Austin Argentieri, Raymond H Mak, Lynne S Cox, Andrew S Brack, Gordan Lauc, David Furman, Jason D Buenrostro, Björn Schumacher, Jamie N Justice, Tina Woods, David Gobel, Viviana I Perez, David A Sinclair, Andrea B Maier, Nir Barzilai, Michael P Snyder, Tony Wyss-Coray, Steve Horvath, Luigi Ferrucci, Jesse R Poganik, Mahdi Moqri, Vadim N Gladyshev

引用次数: 0

Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials.

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.

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.

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":"https://doi.org/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

Alarmingly large care deficits globally for people living with dementia and disability.

IF 17

Nature aging Pub Date : 2025-03-21 DOI: 10.1038/s43587-025-00849-7

引用次数: 0

Interplay of somatic mutations and epigenetic aging clocks.

IF 17

Nature aging Pub Date : 2025-03-19 DOI: 10.1038/s43587-025-00846-w

Wolfgang Wagner

引用次数: 0