Nature aging最新文献_第5页

The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan. 老年保护剂曲美替尼和雷帕霉素加用可延长小鼠健康寿命和寿命。

IF 17

Nature aging Pub Date : 2025-05-28 DOI: 10.1038/s43587-025-00876-4

Lisonia Gkioni, Tobias Nespital, Maarouf Baghdadi, Carolina Monzó, Jitin Bali, Taim Nassr, Anna Lena Cremer, Andreas Beyer, Joris Deelen, Heiko Backes, Sebastian Grönke, Linda Partridge

{"title":"The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan.","authors":"Lisonia Gkioni, Tobias Nespital, Maarouf Baghdadi, Carolina Monzó, Jitin Bali, Taim Nassr, Anna Lena Cremer, Andreas Beyer, Joris Deelen, Heiko Backes, Sebastian Grönke, Linda Partridge","doi":"10.1038/s43587-025-00876-4","DOIUrl":"https://doi.org/10.1038/s43587-025-00876-4","url":null,"abstract":"Suppression of the insulin-IGF-mTORC1-Ras network ameliorates aging in animals. Many drugs have targets in the network because of its roles in cancer and metabolic disease and are candidates for repurposing as geroprotectors. Rapamycin, an established geroprotective drug, blocks mTORC1 signaling, and trametinib inhibits the Ras-MEK-ERK pathway. In this study, we assessed survival and health of male and female mice treated with trametinib, rapamycin or their combination. We show here that trametinib treatment extended lifespan in both sexes and that its combination with rapamycin was additive. Combination treatment reduced liver tumors in both sexes and spleen tumors in male mice, blocked the age-related increase in brain glucose uptake and strongly reduced inflammation in brain, kidney, spleen and muscle and circulating levels of pro-inflammatory cytokines. We conclude that trametinib is a geroprotector in mice and that its combination with rapamycin is more effective than either drug alone, making the combination a candidate for repurposing as a gerotherapy in humans.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176372","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

Mitochondrial clonal mosaicism encodes a biphasic molecular clock of aging. 线粒体克隆嵌合体编码衰老的双相分子钟。

IF 17

Nature aging Pub Date : 2025-05-27 DOI: 10.1038/s43587-025-00890-6

Zhenguo Wang, Zhe Li, Hongyu Liu, Chenghua Yang, Xin Li

{"title":"Mitochondrial clonal mosaicism encodes a biphasic molecular clock of aging.","authors":"Zhenguo Wang, Zhe Li, Hongyu Liu, Chenghua Yang, Xin Li","doi":"10.1038/s43587-025-00890-6","DOIUrl":"https://doi.org/10.1038/s43587-025-00890-6","url":null,"abstract":"Mitochondria rapidly accumulate mutations throughout a lifetime, potentially acting as a molecular clock for aging and disease. We profiled mitochondrial RNA across 47 human tissues from 838 individuals, revealing rapid development of clonal mosaicism with two distinct tissue-specific aging signatures. Tissues with constant cellular turnover such as the gastrointestinal tract or skin exhibit accelerated accumulation of sporadic mutations and clonal expansions, implicating increased susceptibility to age-related tumorigenesis and dysfunction. By contrast, post-mitotic tissues, such as the heart and brain, accumulate mutations at deterministic hotspots (tissue-specific, recurrently mutated sites), reflecting the cumulative burden of high energy demand and mitochondrial turnover independent of cell division. These findings support a biphasic model of the mitochondrial clock: stochastic clonal expansion of sporadic replication errors in proliferative tissues, versus age-dependent heteroplasmy increases at hotspots in high-metabolic tissues. This mutational landscape provides a map of tissue-specific vulnerabilities during aging and offers potential therapeutic targets.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163299","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

Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity. 体对脑胰岛素和Notch信号通过神经元CREB活动调节记忆。

IF 17

Nature aging Pub Date : 2025-05-27 DOI: 10.1038/s43587-025-00873-7

Shiyi Zhou, Katherine E Novak, Rachel Kaletsky, Yifei Weng, Jonathan St Ange, Morgan E Stevenson, Erik Toraason, Yanping Zhang, Wenhong Zhang, Meng-Qiu Dong, Coleen T Murphy

{"title":"Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity.","authors":"Shiyi Zhou, Katherine E Novak, Rachel Kaletsky, Yifei Weng, Jonathan St Ange, Morgan E Stevenson, Erik Toraason, Yanping Zhang, Wenhong Zhang, Meng-Qiu Dong, Coleen T Murphy","doi":"10.1038/s43587-025-00873-7","DOIUrl":"https://doi.org/10.1038/s43587-025-00873-7","url":null,"abstract":"While memory regulation is predominantly understood as autonomous to neurons, factors outside the brain can also affect neuronal function. In Caenorhabditis elegans, the insulin/IGF-1-like signaling (IIS) pathway regulates longevity, metabolism and memory: long-lived daf-2 insulin/IGF-1 receptor mutants more than double memory duration after a single training session, and it was assumed that memory regulation was strictly neuronal. However, here we show that degradation of DAF-2 in the hypodermis also greatly extends memory, via expression of the diffusible Notch ligand, OSM-11, which in turn activates Notch signaling in neurons. Single-nucleus RNA sequencing of neurons revealed increased expression of CREB and other memory genes. Furthermore, in aged animals, activation of the hypodermal IIS-Notch pathway as well as OSM-11 overexpression rescue both memory and learning via CREB activity. Thus, insulin signaling in the liver-like hypodermis non-autonomously regulates neuronal function, providing a systemic connection between metabolism and memory through IIS-Notch-CREB signaling from the body to the brain.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164454","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

Emerging role of mitochondrial calcium levels in cellular senescence and in switching cell fates. 线粒体钙水平在细胞衰老和细胞命运转换中的新作用。

IF 17

Nature aging Pub Date : 2025-05-26 DOI: 10.1038/s43587-025-00887-1

Céline Margand, Pablo Morgado-Cáceres, Ulises Ahumada-Castro, J César Cárdenas, Nadine Martin, David Bernard

引用次数: 0

Reference centiles for intrinsic capacity to monitor clinical health outcomes in real-world primary care cohorts. 在现实世界初级保健队列中监测临床健康结果的内在能力的参考百分位数。

IF 17

Nature aging Pub Date : 2025-05-13 DOI: 10.1038/s43587-025-00861-x

Philipe de Souto Barreto, Wan-Hsuan Lu, Neda Tavassoli, Fatemeh Nourhashémi, Renato Gorga Bandeira de Mello, Eduardo Ferriolli, Sophie Guyonnet, Yves Rolland, Maria Eugenia Soto Martín, Bruno Vellas

{"title":"Reference centiles for intrinsic capacity to monitor clinical health outcomes in real-world primary care cohorts.","authors":"Philipe de Souto Barreto, Wan-Hsuan Lu, Neda Tavassoli, Fatemeh Nourhashémi, Renato Gorga Bandeira de Mello, Eduardo Ferriolli, Sophie Guyonnet, Yves Rolland, Maria Eugenia Soto Martín, Bruno Vellas","doi":"10.1038/s43587-025-00861-x","DOIUrl":"https://doi.org/10.1038/s43587-025-00861-x","url":null,"abstract":"Intrinsic capacity (IC) refers to physical and mental capacities that determine healthy aging. IC is the central element of the World Health Organization care pathway 'Integrated Care for Older People' (ICOPE). However, the operationalization of a composite IC measurement in clinical settings remains to be defined. We used screening data from ICOPE implementation in a real-life population of 27,706 adults 60 years or older that were users of primary care services to elaborate and cross-validate IC scores and centile values for men and women. Here, we show that IC centiles were cross-sectionally associated with comorbidity, frailty and limitations in both activities of daily living and instrumental activities of daily living. External validation using populations from high-income (French INSPIRE-T cohort) and upper-middle-income (ICOPE Brazil) countries validated the associations between IC centiles and clinical outcomes. The IC centiles developed using ICOPE screening data constitute a standardized parameter to monitor individual and population IC through a clinically friendly approach.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056936","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

Author Correction: Single-cell and spatial RNA sequencing identify divergent microenvironments and progression signatures in early- versus late-onset prostate cancer. 作者更正：单细胞和空间RNA测序鉴定了早发性前列腺癌与晚发性前列腺癌不同的微环境和进展特征。

IF 17

Nature aging Pub Date : 2025-05-12 DOI: 10.1038/s43587-025-00892-4

Yifei Cheng, Bingxin Liu, Junyi Xin, Xiaobin Wu, Wenchao Li, Jinwei Shang, Jiajin Wu, Zhengdong Zhang, Bin Xu, Mulong Du, Gong Cheng, Meilin Wang

引用次数: 0

The advantages and challenges of disability-free survival as outcome measure in clinical studies. 无残疾生存在临床研究中的优势和挑战。

IF 17

Nature aging Pub Date : 2025-05-01 DOI: 10.1038/s43587-025-00853-x

Johannes T Neumann, John J McNeil

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

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

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