Nature agingPub Date : 2025-10-03DOI: 10.1038/s43587-025-00989-w
Nektarios Tavernarakis
{"title":"Phase separation meets energy generation to boost longevity","authors":"Nektarios Tavernarakis","doi":"10.1038/s43587-025-00989-w","DOIUrl":"10.1038/s43587-025-00989-w","url":null,"abstract":"Bai and colleagues show that specialized translation hubs called mitochondria-associated translation organelles (MATOs) form by liquid–liquid phase separation on the mitochondrial surface. MATOs congregate ribosomes and specific mRNAs to supply key proteins on-site and thereby uphold mitochondrial integrity and function. Persistent association of MATOs with mitochondria enhances stress resistance and extends lifespan.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 10","pages":"1936-1938"},"PeriodicalIF":19.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226540","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}
Nature agingPub Date : 2025-09-30DOI: 10.1038/s43587-025-00968-1
Kefan Wang, Wei He, Zhe Gong, Jun Gao, Tianyou Gao, Nan Pan, Dongze Wu, Yijie Yang, Zhuang Li, Xing Zhao, Mingliang Ji, Shuying Shen
{"title":"ZDHHC11-mediated palmitoylation alleviates chondrocyte senescence and serves as a therapeutic target for osteoarthritis.","authors":"Kefan Wang, Wei He, Zhe Gong, Jun Gao, Tianyou Gao, Nan Pan, Dongze Wu, Yijie Yang, Zhuang Li, Xing Zhao, Mingliang Ji, Shuying Shen","doi":"10.1038/s43587-025-00968-1","DOIUrl":"https://doi.org/10.1038/s43587-025-00968-1","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a whole-joint disorder that interferes with the quality of life in older individuals. Here we report that ZDHHC11 is highly expressed in articular chondrocytes but is downregulated in the degenerated cartilage of aged mice and patients with OA. ZDHHC11 prevents chondrocyte senescence and promotes cartilage anabolism, culminating in an improved OA phenotype. The deletion of Zdhhc11 in mice (Zdhhc11<sup>fl/fl</sup>) exacerbates OA progression in a destabilized medial meniscus model. Specifically, we identify ZDHHC11 as a key palmitoyltransferase whose depletion leads to a GNB2-dependent E3 ubiquitin ligase-mediated proteasomal degradation of APOD. Mechanistically, ZDHHC11-mediated palmitoylation alleviates OA progression by deactivating the GATA4-P65 signaling pathway. We also propose an original lipid nanoparticle-based platform for Zdhhc11 mRNA delivery to rejuvenate impaired cartilage by specifically targeting chondrocytes in vivo. Collectively, ZDHHC11-dependent palmitoylation is essential for ameliorating OA, and the targeted delivery of ZDHHC11 may serve as a promising strategy for future OA treatment.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202592","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":"Elastin-derived extracellular matrix fragments drive aging through innate immune activation.","authors":"Junzhi Yi, Yixuan Wang, Hairu Sui, Zhichu Chen, Tianning Ye, Yuliang Zhong, Jingyi Qian, Bingbing Wu, Jiayun Huang, Tian Tian, Fangyuan Bao, Xuri Chen, Xiao Xiao, Jiasheng Wang, Jiajie Hu, Yujuan Xie, Hui Zhang, Pan Jin, Xiaoping Xia, Xudong Yao, Yishan Chen, Zi Yin, Weiliang Shen, Jing Zhou, Xiaohui Zou, Hua Liu, Hongwei Ouyang","doi":"10.1038/s43587-025-00961-8","DOIUrl":"https://doi.org/10.1038/s43587-025-00961-8","url":null,"abstract":"<p><p>The roles of cells in systemic aging have been systematically investigated, while the roles of the extracellular matrix (ECM) and its degradation have been largely overlooked. Herein, we show that the serum contents of elastin-, hyaluronic acid- and fibronectin-derived fragments are all positively correlated with age. Elastin-derived fragments exhibited the most potent lifespan-shortening effects in mice and a positive correlation with various aging indicators in a human cohort (n = 1,068). Mechanistically, the VGVAPG oligopeptide (E-motif) in elastin-derived fragments activated monocytes and macrophages through NEU1, a component of the elastin receptor complex, which consequently caused an inflammatory response. Therapeutically, a NEU1 inhibitor extended lifespan by up to 17% in wild-type naturally aged mice and alleviated aging-related phenotypes in wild-type mice, immune-humanized mice and pigs. This study uncovers that degraded ECM acts as a circulating driver of aging, providing an anti-aging intervention strategy focused on particular elastin fragment signals.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194233","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}
Nature agingPub Date : 2025-09-26DOI: 10.1038/s43587-025-00980-5
Takeshi Iwatsubo
{"title":"A Japanese registry for optimizing the safe use of anti-amyloid therapies for Alzheimer’s disease in Japan","authors":"Takeshi Iwatsubo","doi":"10.1038/s43587-025-00980-5","DOIUrl":"10.1038/s43587-025-00980-5","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 10","pages":"1917-1919"},"PeriodicalIF":19.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180742","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}
Nature agingPub Date : 2025-09-25DOI: 10.1038/s43587-025-00966-3
Monica Bodogai, Bongsoo Park, Fatima-Zohra Braikia, Fnu Naqing, Konda Kumaraswami, Chen Chen, Emeline Ragonnaud, Sharon Stack, Steffen Ormanns, Michael Günther, Hellen Ishikawa-Ankerhold, Supriyo De, Luigi Ferrucci, Ranjan Sen, Zhana Duren, Isabel Beerman, Arya Biragyn
{"title":"A distinct population of CD8+ T cells expressing CD39 and CD73 accumulates with age and supports cancer progression","authors":"Monica Bodogai, Bongsoo Park, Fatima-Zohra Braikia, Fnu Naqing, Konda Kumaraswami, Chen Chen, Emeline Ragonnaud, Sharon Stack, Steffen Ormanns, Michael Günther, Hellen Ishikawa-Ankerhold, Supriyo De, Luigi Ferrucci, Ranjan Sen, Zhana Duren, Isabel Beerman, Arya Biragyn","doi":"10.1038/s43587-025-00966-3","DOIUrl":"10.1038/s43587-025-00966-3","url":null,"abstract":"Age-related increases in cancer have traditionally been attributed to compromised antitumor immunity of exhausted and dysfunctional CD8⁺ T cells. Here we provide an alternative mechanism: in aging, cancer also progresses with the help of fully functional CD8⁺ T cells. These transcriptionally and epigenetically distinct cells (termed double-positive CD8+ T cells (DP8)) express CD39, CD73, CD101 and CXCR6 on their surface and accumulate during healthy aging in mice, requiring B cells presenting cognate antigens. In aged mice, progressing tumors recruit DP8 cells via the CXCL16–CXCR6 axis to suppress antitumor CD4+ T cells in an ADP/adenosine-dependent manner, and targeting DP8 cell function or recruitment can reverse tumor growth in aged mice. This tumor-promoting mechanism of DP8 cells appears to be conserved in older humans, as we detected DP8-like cells in various tumors, including late-onset breast cancer. We propose that this tumor-promoting role of CD8+ T cells should be considered in the development of therapeutics tailored for older humans. Bodogai et al. identify a unique subset of CD8+ T cells expressing CD39 and CD73 that accumulate during aging and are recruited to and actively promote tumor progression by suppressing antitumor CD4+ T cells. Targeting their function or recruitment attenuates tumor growth in aged mice.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 10","pages":"2055-2069"},"PeriodicalIF":19.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152453","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}
Nature agingPub Date : 2025-09-24DOI: 10.1038/s43587-025-00957-4
Gabriele Civiletto, Dario Brunetti, Giulia Lizzo, Kamila Muller, Guillaume E. Jacot, Ioanna Daskalaki, Federico Sizzano, Minji Huh, Ivano Di Meo, Maria Nicol Colombo, José L. Sanchez-Garcia, Bertrand J. Bétrisey, Alix Zollinger, Patricia Lino, Christopher Neal, Anne-Laure Egesipe, Joy Richard, Myriam Chimen, Aurélie Hermant, Benjamin Brinon, Lorane Texari, Sylviane Metairon, Mohammed Adnan Qureshi, Dhaval S. Patel, Siva A. Vanapalli, Marco Malavolta, Arwen W. Gao, Amelia Lalou, Mauro Provinciali, Fiorenza Orlando, Valeria Tiranti, Robert T. Brooke, Steve Horvath, Johan Auwerx, Jerome N. Feige, Philipp Gut
{"title":"Herbal terpenoids activate autophagy and mitophagy through modulation of bioenergetics and protect from metabolic stress, sarcopenia and epigenetic aging","authors":"Gabriele Civiletto, Dario Brunetti, Giulia Lizzo, Kamila Muller, Guillaume E. Jacot, Ioanna Daskalaki, Federico Sizzano, Minji Huh, Ivano Di Meo, Maria Nicol Colombo, José L. Sanchez-Garcia, Bertrand J. Bétrisey, Alix Zollinger, Patricia Lino, Christopher Neal, Anne-Laure Egesipe, Joy Richard, Myriam Chimen, Aurélie Hermant, Benjamin Brinon, Lorane Texari, Sylviane Metairon, Mohammed Adnan Qureshi, Dhaval S. Patel, Siva A. Vanapalli, Marco Malavolta, Arwen W. Gao, Amelia Lalou, Mauro Provinciali, Fiorenza Orlando, Valeria Tiranti, Robert T. Brooke, Steve Horvath, Johan Auwerx, Jerome N. Feige, Philipp Gut","doi":"10.1038/s43587-025-00957-4","DOIUrl":"10.1038/s43587-025-00957-4","url":null,"abstract":"Small molecular food components contribute to the health benefits of diets rich in fruits, vegetables, herbs and spices. The cellular mechanisms by which noncaloric bioactives promote healthspan are not well understood, limiting their use in disease prevention. Here, we deploy a whole-organism, high-content screen in zebrafish to profile food-derived compounds for activation of autophagy, a cellular quality control mechanism that promotes healthy aging. We identify thymol and carvacrol as activators of autophagy and mitophagy through a transient dampening of the mitochondrial membrane potential. Chemical stabilization of thymol-induced mitochondrial depolarization blocks mitophagy activation, suggesting a mechanism originating from the mitochondrial membrane. Supplementation with thymol prevents excess liver fat accumulation in a mouse model of diet-induced obesity, improves pink-1-dependent heat stress resilience in Caenorhabditis elegans, and slows the decline of skeletal muscle performance while delaying epigenetic aging in SAMP8 mice. Thus, terpenoids from common herbs promote autophagy during aging and metabolic overload, making them attractive molecules for nutrition-based healthspan promotion. Using a zebrafish-based screen, Civiletto and colleagues identify the herb-derived metabolites thymol and carvacrol as activators of autophagy and mitophagy, demonstrating their therapeutic potential in C. elegans and mouse models.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 10","pages":"2003-2021"},"PeriodicalIF":19.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43587-025-00957-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139904","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}
Nature agingPub Date : 2025-09-24DOI: 10.1038/s43587-025-00982-3
{"title":"Molecular marker of cochlear aging and hearing loss in primates","authors":"","doi":"10.1038/s43587-025-00982-3","DOIUrl":"10.1038/s43587-025-00982-3","url":null,"abstract":"Single-nucleus transcriptomic and histopathological analyses of the cochlea of aged macaques identified multiple features of degeneration, including accelerated hair cell loss, senescence of spiral ganglion neurons with neuroinflammation, and stria vascularis atrophy. Of note, reduced protein levels of a transmembrane transporter are a pivotal molecular signature of hair cell aging.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 10","pages":"1944-1945"},"PeriodicalIF":19.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139897","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}
Nature agingPub Date : 2025-09-23DOI: 10.1038/s43587-025-00985-0
HaiYang Wang, Zhongwei Huang, Xingyu Shen, Yaelim Lee, XinJie Song, Chang Shu, Lik Hang Wu, Leroy Sivappiragasam Pakkiri, Poh Leong Lim, Xi Zhang, Chester Lee Drum, Jin Zhu, Rong Li
{"title":"Publisher Correction: Rejuvenation of aged oocyte through exposure to young follicular microenvironment","authors":"HaiYang Wang, Zhongwei Huang, Xingyu Shen, Yaelim Lee, XinJie Song, Chang Shu, Lik Hang Wu, Leroy Sivappiragasam Pakkiri, Poh Leong Lim, Xi Zhang, Chester Lee Drum, Jin Zhu, Rong Li","doi":"10.1038/s43587-025-00985-0","DOIUrl":"10.1038/s43587-025-00985-0","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 10","pages":"2142-2142"},"PeriodicalIF":19.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43587-025-00985-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133221","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}