Nature aging最新文献_第7页

Quasi-spatial single-cell transcriptome based on physical tissue properties defines early aging associated niche in liver. 基于物理组织特性的准空间单细胞转录组定义了肝脏早期衰老相关的生态位。

IF 17

Nature aging Pub Date : 2025-05-01 Epub Date: 2025-05-05 DOI: 10.1038/s43587-025-00857-7

Kwon Yong Tak, Juyeon Kim, Myungsun Park, Wooseok Kim, Seoyeong Lee, Narae Park, Min Jeong Kim, Ju-Bin Kang, Yongjun Koh, Hae Young Yang, Min Kyu Yum, Injune Kim, Yong Ryoul Yang, Won-Il Jeong, Jinsung Yang, Cheolju Lee, Chuna Kim, Jong-Eun Park

{"title":"Quasi-spatial single-cell transcriptome based on physical tissue properties defines early aging associated niche in liver.","authors":"Kwon Yong Tak, Juyeon Kim, Myungsun Park, Wooseok Kim, Seoyeong Lee, Narae Park, Min Jeong Kim, Ju-Bin Kang, Yongjun Koh, Hae Young Yang, Min Kyu Yum, Injune Kim, Yong Ryoul Yang, Won-Il Jeong, Jinsung Yang, Cheolju Lee, Chuna Kim, Jong-Eun Park","doi":"10.1038/s43587-025-00857-7","DOIUrl":"10.1038/s43587-025-00857-7","url":null,"abstract":"Aging is associated with the accumulation of senescent cells, which are triggered by tissue injury response and often escape clearance by the immune system. The specific traits and diversity of these cells in aged tissues, along with their effects on the tissue microenvironment, remain largely unexplored. Despite the advances in single-cell and spatial omics technologies to understand complex tissue architecture, senescent cell populations are often neglected in general analysis pipelines due to their scarcity and the technical bias in current omics toolkits. Here we used the physical properties of tissue to enrich the age-associated fibrotic niche and subjected them to single-cell RNA sequencing and single-nuclei ATAC sequencing (ATAC-seq) analysis and named this method fibrotic niche enrichment sequencing (FiNi-seq). Fibrotic niche of the tissue was selectively enriched based on its resistance to enzymatic digestion, enabling quasi-spatial analysis. We profiled young and old livers of male mice using FiNi-seq, discovered Wif1- and Smoc1-producing mesenchymal cell populations showing senescent phenotypes, and investigated the early immune responses within this fibrotic niche. Finally, FiNi-ATAC-seq revealed age-associated epigenetic changes enriched in fibrotic niche cells. Thus, our quasi-spatial, single-cell profiling method allows the detailed analysis of initial aging microenvironments, providing potential therapeutic targets for aging prevention.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"929-949"},"PeriodicalIF":17.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059484","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

Regeneration leads to global tissue rejuvenation in aging sexual planarians. 再生导致老龄性涡虫的整体组织年轻化。

IF 17

Nature aging Pub Date : 2025-05-01 Epub 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":"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":"780-798"},"PeriodicalIF":17.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782202","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 : 2025-05-01 Epub 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":"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":"883-896"},"PeriodicalIF":17.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743201","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

Replacement as an aging intervention. 替代作为一种老龄化干预。

IF 17

Nature aging Pub Date : 2025-05-01 Epub Date: 2025-05-08 DOI: 10.1038/s43587-025-00858-6

Sierra Lore, Jesse R Poganik, Anthony Atala, George Church, Vadim N Gladyshev, Morten Scheibye-Knudsen, Eric Verdin

{"title":"Replacement as an aging intervention.","authors":"Sierra Lore, Jesse R Poganik, Anthony Atala, George Church, Vadim N Gladyshev, Morten Scheibye-Knudsen, Eric Verdin","doi":"10.1038/s43587-025-00858-6","DOIUrl":"10.1038/s43587-025-00858-6","url":null,"abstract":"Substantial progress in aging research continues to deepen our understanding of the fundamental mechanisms of aging, yet there is a lack of interventions conclusively shown to attenuate the processes of aging in humans. By contrast, replacement interventions such as joint replacements, pacemaker devices and transplant therapies have a long history of restoring function in injury or disease contexts. Here, we consider biological and synthetic replacement-based strategies as aging interventions. We discuss innovations in tissue engineering, such as the use of scaffolds or bioprinting to generate functional tissues, methods for enhancing donor-recipient compatibility through genetic engineering and recent progress in both cell therapies and xenotransplantation strategies. We explore synthetic approaches including prostheses, external devices and brain-machine interfaces. Additionally, we evaluate the evidence from heterochronic parabiosis experiments in mice and donor-recipient age-mismatched transplants to consider whether systemic benefits could result from personalized replacement approaches. Finally, we outline key challenges and future directions required to advance replacement therapies as viable, scalable and ethical interventions for aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"750-764"},"PeriodicalIF":17.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061807","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

Stem cell therapies for Parkinson's disease. 帕金森病的干细胞疗法。

IF 17

Nature aging Pub Date : 2025-05-01 DOI: 10.1038/s43587-025-00885-3

Yahyah Aman

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 : 2025-05-01 Epub 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":"897-908"},"PeriodicalIF":17.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677430","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

mRNA metabolism regulator human antigen R (HuR) regulates age-related hearing loss in aged mice. mRNA代谢调节因子人抗原R （HuR）调节老年小鼠年龄相关性听力损失。

IF 17

Nature aging Pub Date : 2025-05-01 Epub Date: 2025-05-20 DOI: 10.1038/s43587-025-00860-y

Siwei Guo, Jieying Cao, Guodong Hong, Yuning Song, Ming Xia, Peipei Li, Wei Yuan, Yu Xiao, Guoqiang Sun, Shuang Liu, Shengda Cao, Jieyu Qi, Xiuli Bi, Ziyi Liu, Yunhao Wu, Wen Li, Xiaoxu Zhao, Jiangang Gao, Renjie Chai, Xiaolong Fu

{"title":"mRNA metabolism regulator human antigen R (HuR) regulates age-related hearing loss in aged mice.","authors":"Siwei Guo, Jieying Cao, Guodong Hong, Yuning Song, Ming Xia, Peipei Li, Wei Yuan, Yu Xiao, Guoqiang Sun, Shuang Liu, Shengda Cao, Jieyu Qi, Xiuli Bi, Ziyi Liu, Yunhao Wu, Wen Li, Xiaoxu Zhao, Jiangang Gao, Renjie Chai, Xiaolong Fu","doi":"10.1038/s43587-025-00860-y","DOIUrl":"10.1038/s43587-025-00860-y","url":null,"abstract":"Age-related hearing loss (ARHL) is among the most prevalent and complex disorders in older adults. However, the pathogenesis of ARHL remains poorly understood. Using a single-cell transcriptomic landscape of mouse cochlea at five time points (1, 2, 5, 12 and 15 months), we found that the levels of human antigen R (HuR)-a classical RNA-binding protein-increase with age. Here we show that HuR is specifically transported from the nucleus to the cytoplasm in hair cells in both aging mice and nonhuman primates. HuR overexpression in cochlea could successfully alleviate ARHL in aged mice. Meanwhile, HuR deficiency led to premature hearing dysfunction characterized by degeneration of stereocilia and the subsequent loss of hair cells. RNA immunoprecipitation sequencing analysis revealed that HuR can bind to messenger RNAs that enable stereocilia maintenance, including Gnai3. Adeno-associated virus-mediated Gnai3 overexpression partially rescues the hearing defects in HuR-deficient mice. Taken together, these findings indicate that HuR is a potential therapeutic target for ARHL.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 5","pages":"848-867"},"PeriodicalIF":17.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113094","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

Promoting health and survival through lowered body temperature. 通过降低体温促进健康和生存。

IF 17

Nature aging Pub Date : 2025-05-01 Epub Date: 2025-04-09 DOI: 10.1038/s43587-025-00850-0

Bruno Conti, Rafael de Cabo

{"title":"Promoting health and survival through lowered body temperature.","authors":"Bruno Conti, Rafael de Cabo","doi":"10.1038/s43587-025-00850-0","DOIUrl":"10.1038/s43587-025-00850-0","url":null,"abstract":"Core body temperature (Tb) is a long-established determinant of longevity across species. In this Perspective, we first summarize evidence demonstrating that reducing Tb increases lifespan and that lowered Tb contributes to the antiaging effects of calorie restriction. Next, we discuss recent data that diverge from prior hypotheses on the mechanisms by which Tb affects longevity, suggesting these are limited neither to the thermodynamics of nonenzymatic chemical reactions, nor reduced formation of mitochondrial reactive oxygen species nor lowered metabolic rate. Instead, recent findings in invertebrates show that cold promotes longevity via specific pathways including nutrient sensing and proteostasis, as well as modulating the thermodynamics of proteins and nucleic acids by changing their structure and function, for example, affecting temperature-sensitive ion channels, long-lived temperature-sensitive dauer mutations, base-pair stability and stem-loop RNA structures. Temperature affects the epigenetic signature and inflammation, and lowering Tb can also induce RNA-binding cold shock proteins, activate cold-sensitive kinases and differential splicing to potentially reshape the cellular environment. Finally, we reflect on important future work and the translational potential of temperature management and temperature mimetics.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"740-749"},"PeriodicalIF":17.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061077","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

New biomarkers for early-stage tau pathology in Alzheimer's disease. 阿尔茨海默病早期tau病理的新生物标志物。

IF 17

Nature aging Pub Date : 2025-05-01 DOI: 10.1038/s43587-025-00854-w

Rongcan Luo, Jin-Tai Yu

引用次数: 0

Ancient viruses sustain mammalian reproduction. 古老的病毒维持着哺乳动物的繁殖。

IF 17

Nature aging Pub Date : 2025-05-01 DOI: 10.1038/s43587-025-00867-5

Caroline A Doherty, Diana J Laird

引用次数: 0