Nature aging最新文献

{"title":"Large-scale network analysis of the cerebrospinal fluid proteome identifies molecular signatures of frontotemporal lobar degeneration.","authors":"Rowan Saloner, Adam M Staffaroni, Eric B Dammer, Erik C B Johnson, Emily W Paolillo, Amy Wise, Hilary W Heuer, Leah K Forsberg, Argentina Lario-Lago, Julia D Webb, Jacob W Vogel, Alexander F Santillo, Oskar Hansson, Joel H Kramer, Bruce L Miller, Jingyao Li, Joseph Loureiro, Rajeev Sivasankaran, Kathleen A Worringer, Nicholas T Seyfried, Jennifer S Yokoyama, Salvatore Spina, Lea T Grinberg, William W Seeley, Lawren VandeVrede, Peter A Ljubenkov, Ece Bayram, Andrea Bozoki, Danielle Brushaber, Ciaran M Considine, Gregory S Day, Bradford C Dickerson, Kimiko Domoto-Reilly, Kelley Faber, Douglas R Galasko, Tania Gendron, Daniel H Geschwind, Nupur Ghoshal, Neill Graff-Radford, Chadwick M Hales, Lawrence S Honig, Ging-Yuek R Hsiung, Edward D Huey, John Kornak, Walter Kremers, Maria I Lapid, Suzee E Lee, Irene Litvan, Corey T McMillan, Mario F Mendez, Toji Miyagawa, Alexander Pantelyat, Belen Pascual, Joseph Masdeu, Henry L Paulson, Leonard Petrucelli, Peter Pressman, Rosa Rademakers, Eliana Marisa Ramos, Katya Rascovsky, Erik D Roberson, Rodolfo Savica, Allison Snyder, Anna Campbell Sullivan, M Carmela Tartaglia, Marijne Vandebergh, Brad F Boeve, Howie J Rosen, Julio C Rojas, Adam L Boxer, Kaitlin B Casaletto","doi":"10.1038/s43587-025-00878-2","DOIUrl":"https://doi.org/10.1038/s43587-025-00878-2","url":null,"abstract":"<p><p>The pathophysiological mechanisms driving disease progression of frontotemporal lobar degeneration (FTLD) and corresponding biomarkers are not fully understood. Here we leveraged aptamer-based proteomics (>4,000 proteins) to identify dysregulated communities of co-expressed cerebrospinal fluid proteins in 116 adults carrying autosomal dominant FTLD mutations (C9orf72, GRN and MAPT) compared with 39 non-carrier controls. Network analysis identified 31 protein co-expression modules. Proteomic signatures of genetic FTLD clinical severity included increased abundance of RNA splicing (particularly in C9orf72 and GRN) and extracellular matrix (particularly in MAPT) modules, as well as decreased abundance of synaptic/neuronal and autophagy modules. The generalizability of genetic FTLD proteomic signatures was tested and confirmed in independent cohorts of (1) sporadic progressive supranuclear palsy-Richardson syndrome and (2) frontotemporal dementia spectrum clinical syndromes. Network-based proteomics hold promise for identifying replicable molecular pathways in adults living with FTLD. 'Hub' proteins driving co-expression of affected modules warrant further attention as candidate biomarkers and therapeutic targets.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087141","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}

{"title":"Ancient viruses sustain mammalian reproduction.","authors":"Caroline A Doherty, Diana J Laird","doi":"10.1038/s43587-025-00867-5","DOIUrl":"https://doi.org/10.1038/s43587-025-00867-5","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083038","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}

{"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":"<p><p>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.</p>","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}

{"title":"Gut microbiota-dependent increase in phenylacetic acid induces endothelial cell senescence during aging.","authors":"Seyed Soheil Saeedi Saravi, Benoit Pugin, Florentin Constancias, Khatereh Shabanian, Marianne Spalinger, Aurélien Thomas, Sylvain Le Gludic, Taraneh Shabanian, Gergely Karsai, Manuel Colucci, Cristina Menni, Ilias Attaye, Xinyuan Zhang, Meret Sarah Allemann, Pratintip Lee, Alessia Visconti, Mario Falchi, Andrea Alimonti, Frank Ruschitzka, Francesco Paneni, Jürg H Beer","doi":"10.1038/s43587-025-00864-8","DOIUrl":"https://doi.org/10.1038/s43587-025-00864-8","url":null,"abstract":"<p><p>Endothelial cell senescence is a key driver of cardiovascular aging, yet little is known about the mechanisms by which it is induced in vivo. Here we show that the gut bacterial metabolite phenylacetic acid (PAA) and its byproduct, phenylacetylglutamine (PAGln), are elevated in aged humans and mice. Metagenomic analyses reveal an age-related increase in PAA-producing microbial pathways, positively linked to the bacterium Clostridium sp. ASF356 (Clos). We demonstrate that colonization of young mice with Clos increases blood PAA levels and induces endothelial senescence and angiogenic incompetence. Mechanistically, we find that PAA triggers senescence through mitochondrial H₂O₂ production, exacerbating the senescence-associated secretory phenotype. By contrast, we demonstrate that fecal acetate levels are reduced with age, compromising its function as a Sirt1-dependent senomorphic, regulating proinflammatory secretion and redox homeostasis. These findings define PAA as a mediator of gut-vascular crosstalk in aging and identify sodium acetate as a potential microbiome-based senotherapy to promote healthy aging.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039440","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}

{"title":"Author Correction: Single-cell and spatial RNA sequencing identify divergent microenvironments and progression signatures in early- versus late-onset prostate cancer.","authors":"Yifei Cheng, Bingxin Liu, Junyi Xin, Xiaobin Wu, Wenchao Li, Jinwei Shang, Jiajin Wu, Zhengdong Zhang, Bin Xu, Mulong Du, Gong Cheng, Meilin Wang","doi":"10.1038/s43587-025-00892-4","DOIUrl":"https://doi.org/10.1038/s43587-025-00892-4","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033638","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}

{"title":"Stem cell therapies for Parkinson's disease.","authors":"Yahyah Aman","doi":"10.1038/s43587-025-00885-3","DOIUrl":"https://doi.org/10.1038/s43587-025-00885-3","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055873","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}

{"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":"https://doi.org/10.1038/s43587-025-00858-6","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-08","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}

{"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":"https://doi.org/10.1038/s43587-025-00857-7","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-05","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}

{"title":"Recycling tRNA fragment 'trash' into treasure.","authors":"Frank A Middleton","doi":"10.1038/s43587-025-00870-w","DOIUrl":"https://doi.org/10.1038/s43587-025-00870-w","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048708","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}

{"title":"Life-course approaches are needed to foster equitable healthy aging.","authors":"Anita van Zwieten, Suraj Samtani, Mouna Sawan, Jo-An Occhipinti, J Jaime Miranda, Saman Khalatbari-Soltani","doi":"10.1038/s43587-025-00875-5","DOIUrl":"https://doi.org/10.1038/s43587-025-00875-5","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059261","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}