Nature aging最新文献

{"title":"The aging extracellular matrix as a missing link in senescent cell accumulation and persistence.","authors":"Natalia Hernández-Bellido, Aida Perramon-Güell, Carlos Anerillas","doi":"10.1038/s43587-026-01127-w","DOIUrl":"https://doi.org/10.1038/s43587-026-01127-w","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848310","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":"Mitigating the Hawthorne effect in aging research.","authors":"David Furman","doi":"10.1038/s43587-026-01126-x","DOIUrl":"https://doi.org/10.1038/s43587-026-01126-x","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848259","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":"Multimodal data analysis reveals asynchronous aging dynamics across female reproductive organs.","authors":"Oleksandra Soldatkina, Laura Ventura-San Pedro, Natàlia Pujol-Gualdo, Allal El Hommad, Jose Miguel Ramirez, Aida Ripoll-Cladellas, Maria Sopena-Rios, Daniel Tabares, Miguel Ángel Pérez-Elena, David Torrents, Jaume Ordi, Marta Melé","doi":"10.1038/s43587-026-01098-y","DOIUrl":"https://doi.org/10.1038/s43587-026-01098-y","url":null,"abstract":"<p><p>Female reproductive aging has systemic health implications, yet tissue-level dynamics remain poorly understood. Here we integrate deep learning analysis of 1,112 histology images with RNA sequencing from 659 samples across seven female reproductive organs in donors aged 20-70 years. We uncover asynchronous trajectories: the ovary ages gradually, whereas the uterus shows an abrupt molecular and morphological shift around menopause. This uterine transition is independently supported by plasma proteomics data from a large population cohort, indicating that organ-linked aging signatures are detectable in circulation. Tissue segmentation highlights the myometrium as strongly age affected, with extracellular matrix remodeling and immune activation. Epithelial tissues also show coordinated age-related remodeling, with a sharp menopausal transition in the vaginal epithelium. Multi-omics factor analysis links these histological changes to nonlinear gene-expression shifts enriched for reproductive traits, including pelvic organ prolapse and age at menarche. Together, these findings establish menopause as a key inflection point in female aging and provide a tissue-resolved, multi-dataset framework for late-life health.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793402","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":"Connecting fragmented aging research through the European Federation for Aging Research.","authors":"Björn Schumacher, Morten Scheibye-Knudsen, Lene Juel Rasmussen, Folkert Kuipers","doi":"10.1038/s43587-026-01128-9","DOIUrl":"https://doi.org/10.1038/s43587-026-01128-9","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793397","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":"Repurposing drugs for the prevention of vascular dementia using evidence from drug target Mendelian randomization","authors":"Victoria Taylor-Bateman,&nbsp;Phazha Bothongo,&nbsp;Venexia Walker,&nbsp;Patrick G. Kehoe,&nbsp;Liv Tybjærg Nordestgaard,&nbsp;Yoav Ben-Shlomo,&nbsp;Neil M. Davies,&nbsp;Dylan M. Williams,&nbsp;Emma L. Anderson","doi":"10.1038/s43587-026-01106-1","DOIUrl":"10.1038/s43587-026-01106-1","url":null,"abstract":"Vascular dementia (VaD) is a devastating cerebrovascular disease with no disease-modifying treatments. Repurposing drugs for known risk factors could have clinical impact. Using Mendelian randomization, we proxied 46 lipid-lowering, antihypertensive and anti-inflammatory drug effects across five VaD outcomes: clinical diagnosis (N = 7,009 cases, N = 899,672 non-cases/controls) and neuroimaging features (max N = 50,559), white matter hyperintensity volume, fractional anisotropy, mean diffusivity and lacunar stroke diagnosis. Beta-1 adrenergic receptor indicated potential benefit (clinical diagnosis: odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.80–1.01; white matter hyperintensity volume: estimated causal effect = −0.03, 95% CI = −0.07–0.00; mean diffusivity: estimated causal effect = −0.18, 95% CI = −0.37–0.00; lacunar stroke: OR = 0.91, 95% CI = 0.80–1.03). Angiotensin-converting enzyme inhibition suggested increased VaD risk (OR = 1.12, 95% CI = 1.01–1.24). Findings remained largely null after multiple-testing correction. Here we show that although little evidence supported repurposing most lipid-lowering, antihypertensive and anti-inflammatory drugs for VaD prevention or treatment, beta-1 adrenergic receptor antagonism could be a promising repurposing candidate, but replication is needed as further data becomes available. Pharmacovigilance studies should examine angiotensin-converting enzyme inhibitors’ potential to increase risk. Repurposing existing drugs for vascular dementia (VaD) could have clinical impact. Here, using Mendelian randomization, researchers tested whether cholesterol, anti-inflammatory or blood pressure drug targets affect risk of VaD, finding little evidence to support repurposing opportunities. A potential benefit was seen for beta-blocker target ADRB1 while ACE inhibition was observed to potentially increase risk of VaD.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"6 4","pages":"905-915"},"PeriodicalIF":19.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43587-026-01106-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727660","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}

{"title":"p21+TREM2+ senescent macrophages fuel inflammaging and metabolic dysfunction-associated steatotic liver disease","authors":"Ivan A. Salladay-Perez,&nbsp;Itzetl Avila,&nbsp;Lizeth Estrada,&nbsp;Andreea C. Alexandru,&nbsp;Cristian Ponce,&nbsp;Anika Dhingra,&nbsp;Grasiela Torres,&nbsp;Christina Y. Deng,&nbsp;Ronak Hegde,&nbsp;Julia Gensheimer,&nbsp;Abhijit Kale,&nbsp;Indra Heckenbach,&nbsp;Simon Hui,&nbsp;Chantle Edillor,&nbsp;Jose A. Soto,&nbsp;Alexander J. Napior,&nbsp;Isaiah Little,&nbsp;Mark Larsen,&nbsp;Jacob Rose,&nbsp;Lia Farahi,&nbsp;Edwin D. J. Lopez Gonzalez,&nbsp;Matthew R. Krieger,&nbsp;Kushan Chowdhury,&nbsp;Mridul Sharma,&nbsp;Yuming Jiang,&nbsp;Kevin Williams,&nbsp;Morten Scheibye-Knudsen,&nbsp;Carla M. Koehler,&nbsp;Jesse G. Meyer,&nbsp;Julia J. Mack,&nbsp;Charles Brenner,&nbsp;Steven J. Bensinger,&nbsp;Cyril Lagger,&nbsp;João Pedro de Magalhães,&nbsp;Birgit Schilling,&nbsp;Rajat Singh,&nbsp;Eric Verdin,&nbsp;Aldons J. Lusis,&nbsp;Anthony J. Covarrubias","doi":"10.1038/s43587-026-01101-6","DOIUrl":"10.1038/s43587-026-01101-6","url":null,"abstract":"Cellular senescence drives chronic sterile inflammation during aging via the senescence-associated secretory phenotype, yet the senescent cell types responsible are poorly defined. Macrophages share multiple features of senescence, including inflammatory secretion, yet whether macrophages can adopt a senescent state remains unclear. Here we identify p21⁺Trem2⁺ senescent macrophages as a major source of inflammaging, using primary mouse and human macrophage models of DNA damage and cholesterol-induced senescence characterized by multi-omic profiling. We found that senescent macrophages exhibit a distinctive p21-TREM2 expression profile and senescence-associated secretory phenotype, driven in part by type I interferon signaling via cytosolic mitochondrial DNA. We also found that senescent macrophage accumulation occurs in aging, metabolic dysfunction-associated steatotic liver disease mouse livers, and is enriched in human cirrhotic liver tissue. Finally, senolytic treatment targeting senescent macrophages reduced liver inflammation and steatosis in both aged mice and mice with metabolic dysfunction-associated steatotic liver disease. These findings establish macrophage senescence as a central driver of chronic inflammation in aging and metabolic liver disease, and a tractable therapeutic target. Salladay-Perez and colleagues explore senescence induction in human and mouse macrophages using multiomic profiling. They characterize a p21+TREM2+ senescent macrophage population, which they functionally implicate in inflammaging and liver disease.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"6 4","pages":"792-815"},"PeriodicalIF":19.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43587-026-01101-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147701386","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}

{"title":"Astrocyte-based CAR immunotherapy against Alzheimer’s disease","authors":"Maria Papatriantafyllou","doi":"10.1038/s43587-026-01115-0","DOIUrl":"10.1038/s43587-026-01115-0","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"6 4","pages":"743-743"},"PeriodicalIF":19.4,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694365","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":"Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging.","authors":"Manish Mishra, Hee-Hoon Kim, Yun-Hee Youm, Elsie Gonzalez-Hurtado, Konstantin Zaitsev, Tamara Dlugos, Irina Shchukina, Christy Gliniak, Eric Ravussin, Subhasis Mohanty, Albert C Shaw, Philipp E Scherer, Maxim N Artyomov, Vishwa Deep Dixit","doi":"10.1038/s43587-026-01107-0","DOIUrl":"10.1038/s43587-026-01107-0","url":null,"abstract":"<p><p>Caloric restriction (CR) extends lifespan across diverse organisms, but the effects of CR on human aging and on healthspan are only beginning to be uncovered. In this study, we applied proteomics to plasma samples collected longitudinally from participants achieving, on average, 14% CR over 2 years as part of the CALERIE trial. We identified that inhibition of the complement pathway is linked to lower inflammaging. In humans, the C3a/C3 ratio was significantly lowered by CR, thus reducing inflammation emanating from three canonical complement pathways. Furthermore, circulating C3a is elevated during aging in humans and in mice; we identified a non-senescent age-associated macrophage subset that expands in visceral fat as the predominant source. In macrophages, C3a-C3AR1 autocrine signaling via extracellular signal-regulated kinase (ERK) regulates age-related inflammation. Intra-adipose administration of a C3a-specific neutralizing antibody reduced inflammaging in mice. In addition, fibroblast growth factor 21 (FGF21) overexpression and deficiency of phospholipase A2 group VII (PLA2G7/lp-PLA2), which enhance lifespan and healthspan in mice, lowered C3a in aging. Thus, complement C3a reduction is a metabolically regulated inflammatory checkpoint that can be harnessed to attenuate inflammaging.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679793","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":"Biological sex shapes divergent trajectories of immune aging","authors":"","doi":"10.1038/s43587-026-01110-5","DOIUrl":"10.1038/s43587-026-01110-5","url":null,"abstract":"Single-cell profiling of nearly 1,000 individuals reveals that immune aging follows distinct cellular and transcriptional trajectories in female and male adults, with stronger cellular and molecular remodeling in female than male participants.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"6 4","pages":"750-751"},"PeriodicalIF":19.4,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655547","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":"Single-cell analysis of the human immune system reveals sex-specific dynamics of immunosenescence","authors":"Maria Sopena-Rios,&nbsp;Aida Ripoll-Cladellas,&nbsp;Fatemeh Omidi,&nbsp;Sara Ballouz,&nbsp;Jose Alquicira-Hernandez,&nbsp;Roy Oelen,&nbsp;Alex W. Hewitt,&nbsp;Lude Franke,&nbsp;Monique G. P. van der Wijst,&nbsp;Joseph E. Powell,&nbsp;Marta Melé","doi":"10.1038/s43587-026-01099-x","DOIUrl":"10.1038/s43587-026-01099-x","url":null,"abstract":"Immunosenescence, the progressive aging of the immune system, is characterized by changes in immune cell composition and function that increase susceptibility to disease. However, how biological sex shapes immune aging at the cellular level remains poorly understood. Here, we analyze single-cell RNA sequencing data from the peripheral blood mononuclear cells of 982 female and male donors across adulthood. We find that aging drives sexually dimorphic compositional and transcriptional changes, with female individuals exhibiting stronger immune remodeling. Female-specific changes include the expansion of cytotoxic CD8⁺ effector memory T cell subsets and inflammatory monocytes, and age-related shifts in the CD4⁺ central memory T cell populations involved in autoimmunity. In contrast, a subset of male participants shows an age-associated expansion of a B cell population linked to an asymptomatic precursor state of chronic lymphocytic leukemia. Together, these findings reveal sex-specific hallmarks of immunosenescence and highlight the importance of incorporating biological sex into strategies aimed at promoting healthy immune aging. Sopena-Rios and colleagues profile single-cell transcriptomic data from nearly 1,000 female and male participants across the adult lifespan and identify sex-specific changes in inflammation, autoimmunity and disease risk, with more widespread age-related immune remodeling in female participants.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"6 4","pages":"932-949"},"PeriodicalIF":19.4,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655639","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}