{"title":"Extracellular vesicles from antler blastema progenitor cells reverse bone loss and mitigate aging-related phenotypes in mice and macaques.","authors":"Yiming Hao, Beibei Yu, Mingze Qin, Tao Qin, Jianhong Wang, Yitao Wei, Chengxiang Zhao, Yaowen Xing, Yuan Yuan, Tingfeng Xue, Borui Xue, Yali Zhang, Hongdi Huang, Xiaomei Yu, Yunchao Ji, Minghao Qiu, Yufang Zhou, Bing Xia, Teng Ma, Shengyou Li, Haining Wu, Xue Gao, Yujie Yang, Lingli Guo, Yongfeng Zhang, Zhenguo Wang, Huiling Sun, Xueli Gao, Zujian Huang, Longbao Lv, Dongdong Wu, Zhipeng Li, Yonggang Yao, Wen Wang, Zhuojing Luo, Qiang Qiu, Jinghui Huang","doi":"10.1038/s43587-025-00918-x","DOIUrl":"https://doi.org/10.1038/s43587-025-00918-x","url":null,"abstract":"<p><p>Antler blastema progenitor cells (ABPCs) are a distinct population of skeletal mesenchymal stem cells found in regenerating deer antlers, with strong stemness and renewal capacity in vitro. Stem cell-derived extracellular vesicles (EVs) are emerging as potential therapeutic candidates that can mediate donor cells' beneficial effects. Here, we tested the effects of ABPC-derived EVs (EVs<sup>ABPC</sup>) on aging in mice and rhesus macaques (Macaca mulatta). We identified a variety of unique factors in EVs<sup>ABPC</sup> and showed that in vitro, EVs<sup>ABPC</sup> attenuated phenotypes of senescence in bone marrow stem cells. In aged mice and macaques, EVs<sup>ABPC</sup> substantially increased femoral bone mineral density. Further, intravenous EVs<sup>ABPC</sup> improved physical performance, enhanced cognitive function and reduced systemic inflammation in aged mice, while reversing epigenetic age by over 3 months. In macaques, EV<sup>ABPC</sup> treatment was also neuroprotective, reduced inflammation, improved locomotor function and reduced epigenetic age by over 2 years. Our findings position ABPCs as an emerging and practical source of EVs with translational value for healthy aging interventions.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639140","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 : 2025-07-14DOI: 10.1038/s43587-025-00889-z
Krystyna Mazan-Mamczarz, Dimitrios Tsitsipatis, Bennett G Childs, Angelica E Carr, Carla Rocha Dos Santos, Carlos Anerillas, Brigette Romero, Jordan M Gregg, Charnae' Henry-Smith, Ada N Okereke, Marc Michel, Rachel Munk, Jennifer L Martindale, Yulan Piao, Jinshui Fan, Maria O Hernandez, Noemi Kedei, Michael L Viacheslavov, Madeline M F Wong, Olga V Fedorova, Mona Batish, Supriyo De, Darren J Baker, Myriam Gorospe, Allison B Herman
{"title":"Single-cell and spatial transcriptomics map senescent vascular cells in arterial remodeling during atherosclerosis in mice.","authors":"Krystyna Mazan-Mamczarz, Dimitrios Tsitsipatis, Bennett G Childs, Angelica E Carr, Carla Rocha Dos Santos, Carlos Anerillas, Brigette Romero, Jordan M Gregg, Charnae' Henry-Smith, Ada N Okereke, Marc Michel, Rachel Munk, Jennifer L Martindale, Yulan Piao, Jinshui Fan, Maria O Hernandez, Noemi Kedei, Michael L Viacheslavov, Madeline M F Wong, Olga V Fedorova, Mona Batish, Supriyo De, Darren J Baker, Myriam Gorospe, Allison B Herman","doi":"10.1038/s43587-025-00889-z","DOIUrl":"https://doi.org/10.1038/s43587-025-00889-z","url":null,"abstract":"<p><p>Growing evidence suggests that the induction of cellular senescence in vascular cells is causally linked to the etiology of cardiovascular diseases. To investigate systematically the heterogeneity of senescent vascular cells in atherosclerosis, we used a high-fat diet and PCSK9 overexpression to induce atherosclerosis in a senescence reporter mouse model (p16-tdTomato<sup>+/-</sup>) and performed single-cell RNA sequencing on whole aortas. Using the SenMayo and CellAge gene sets, we identified four clusters of vascular smooth muscle cells (VSMCs), fibroblasts and T cells enriched in features of senescence, which were reduced upon treatment with the senolytic agent ABT-737. We then derived a global senescence signature of atherosclerosis including Spp1, Ctsb and Tnfrsf11b mRNAs. We validated the enrichment of these mRNAs in senescence by using spatial transcriptomics in a second mouse model of atherosclerosis and senolysis (Ldlr<sup>-/-</sup>; p16-3MR), as well as by analyzing in vitro models of human VSMC senescence. Our results uncover a vascular-specific transcriptomic signature of senescence that may be exploited for tracking and treating age-related vascular diseases.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639142","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":"Characterizing primary and secondary senescence in vivo.","authors":"Yuko Sogabe, Hirofumi Shibata, Mio Kabata, Akito Tanaka, Kanae Mitsunaga, Kazunori Sunadome, May Nakajima-Koyama, Michitada Hirano, Eisuke Nishida, Knut Woltjen, Hiroshi Seno, Yasuhiro Yamada, Takuya Yamamoto","doi":"10.1038/s43587-025-00917-y","DOIUrl":"https://doi.org/10.1038/s43587-025-00917-y","url":null,"abstract":"<p><p>There is robust evidence that senescence can be propagated in vitro through mechanisms including the senescence-associated secretory phenotype, resulting in the non-cell-autonomous induction of secondary senescence. However, the induction, regulation and physiological role of secondary senescence in vivo remain largely unclear. Here we generated senescence-inducible mouse models expressing either the constitutively active form of MEK1 or MKK6 and mCherry, to map primary and secondary senescent cells. Our models recapitulate characteristic features of senescence and demonstrate that primary and secondary phenotypes are highly tissue- and inducer-dependent. Spatially resolved RNA expression analyses at the single-cell level reveal that each senescence induction results in a unique transcriptional profile-even within cells of the same cell type-explaining the heterogeneity of senescent cells in vivo. Furthermore, we show that interleukin-1β, primarily derived from macrophages, induces secondary phenotypes. Our findings provide insight into secondary senescence in vivo and useful tools for understanding and manipulating senescence during aging.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621631","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 : 2025-07-08DOI: 10.1038/s43587-025-00923-0
Jinkook Lee, Ava Bindas, David Knapp, Sara Adar
{"title":"Insights into bridging disciplines and building measures from the Gateway Exposome Coordinating Center workshop.","authors":"Jinkook Lee, Ava Bindas, David Knapp, Sara Adar","doi":"10.1038/s43587-025-00923-0","DOIUrl":"https://doi.org/10.1038/s43587-025-00923-0","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":""},"PeriodicalIF":17.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593277","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 : 2025-07-01DOI: 10.1038/s43587-025-00931-0
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
{"title":"Author Correction: 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/s43587-025-00931-0","DOIUrl":"10.1038/s43587-025-00931-0","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"1372"},"PeriodicalIF":17.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585992","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 : 2025-07-01Epub Date: 2025-06-04DOI: 10.1038/s43587-025-00883-5
Matías Fuentealba, Laure Rouch, Sophie Guyonnet, Jean-Marc Lemaitre, Philipe de Souto Barreto, Bruno Vellas, Sandrine Andrieu, David Furman
{"title":"A blood-based epigenetic clock for intrinsic capacity predicts mortality and is associated with clinical, immunological and lifestyle factors.","authors":"Matías Fuentealba, Laure Rouch, Sophie Guyonnet, Jean-Marc Lemaitre, Philipe de Souto Barreto, Bruno Vellas, Sandrine Andrieu, David Furman","doi":"10.1038/s43587-025-00883-5","DOIUrl":"10.1038/s43587-025-00883-5","url":null,"abstract":"<p><p>Age-related decline in intrinsic capacity (IC), defined as the sum of an individual's physical and mental capacities, is a cornerstone for promoting healthy aging by prioritizing maintenance of function over disease treatment. However, assessing IC is resource-intensive, and the molecular and cellular bases of its decline are poorly understood. Here we used the INSPIRE-T cohort (1,014 individuals aged 20-102 years) to construct the IC clock, a DNA methylation-based predictor of IC, trained on the clinical evaluation of cognition, locomotion, psychological well-being, sensory abilities and vitality. In the Framingham Heart Study, DNA methylation IC outperforms first-generation and second-generation epigenetic clocks in predicting all-cause mortality, and it is strongly associated with changes in molecular and cellular immune and inflammatory biomarkers, functional and clinical endpoints, health risk factors and lifestyle choices. These findings establish the IC clock as a validated tool bridging molecular readouts of aging and clinical assessments of IC.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"1207-1216"},"PeriodicalIF":17.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228015","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}
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