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":"10.1038/s43587-025-00923-0","url":null,"abstract":"This Meeting Report summarizes the 2025 Gateway Exposome Coordinating Center workshop, which brought together over 80 experts to shape a research agenda that bridges exposome science with Alzheimer’s disease and Alzheimer’s disease-related dementias.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 9","pages":"1659-1662"},"PeriodicalIF":19.4,"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 : 2025-07-07DOI: 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, on behalf of the ALLFTD Consortium
{"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, on behalf of the ALLFTD Consortium","doi":"10.1038/s43587-025-00931-0","DOIUrl":"10.1038/s43587-025-00931-0","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 7","pages":"1372-1372"},"PeriodicalIF":19.4,"publicationDate":"2025-07-07","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 : 2025-07-07DOI: 10.1038/s43587-025-00932-z
Yahyah Aman
{"title":"Tau PET positivity marks early clinical transition in Alzheimer’s disease progression","authors":"Yahyah Aman","doi":"10.1038/s43587-025-00932-z","DOIUrl":"10.1038/s43587-025-00932-z","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 7","pages":"1187-1187"},"PeriodicalIF":19.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585994","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/s43587-025-00914-1
Marcos D. Machado-Fragua, Aurore Fayosse, Julien Dumurgier, Mika Kivimaki, Céline Ben Hassen, Gill Livingston, Claire Paquet, Séverine Sabia, Archana Singh-Manoux
{"title":"Association of midlife hearing impairment and hearing aid use with incident dementia: analysis of two UK-based longitudinal cohort studies","authors":"Marcos D. Machado-Fragua, Aurore Fayosse, Julien Dumurgier, Mika Kivimaki, Céline Ben Hassen, Gill Livingston, Claire Paquet, Séverine Sabia, Archana Singh-Manoux","doi":"10.1038/s43587-025-00914-1","DOIUrl":"10.1038/s43587-025-00914-1","url":null,"abstract":"The prevalence of hearing impairment and dementia increases with age but the nature of their association remains unclear. Using data from two large UK-based cohort studies, we examined the longitudinal association of ‘midlife’ hearing impairment and hearing aid use with incident dementia. We found modest associations and population attributable fractions for reported and measured ‘midlife’ hearing impairment, highlighting the need to consider age at measurement of risk factors in studies that target dementia prevention. Machado-Fragua et al. report modest associations and population attributable fractions for midlife hearing impairment with dementia, highlighting the need to consider age at measurement of risk factors in studies that target dementia prevention.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 9","pages":"1732-1738"},"PeriodicalIF":19.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546702","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 : 2025-07-01DOI: 10.1038/s43587-025-00897-z
Ethan T. Whitman, Maxwell L. Elliott, Annchen R. Knodt, Wickliffe C. Abraham, Tim J. Anderson, Nicholas J. Cutfield, Sean Hogan, David Ireland, Tracy R. Melzer, Sandhya Ramrakha, Karen Sugden, Reremoana Theodore, Benjamin S. Williams, Avshalom Caspi, Terrie E. Moffitt, Ahmad R. Hariri
{"title":"DunedinPACNI estimates the longitudinal Pace of Aging from a single brain image to track health and disease","authors":"Ethan T. Whitman, Maxwell L. Elliott, Annchen R. Knodt, Wickliffe C. Abraham, Tim J. Anderson, Nicholas J. Cutfield, Sean Hogan, David Ireland, Tracy R. Melzer, Sandhya Ramrakha, Karen Sugden, Reremoana Theodore, Benjamin S. Williams, Avshalom Caspi, Terrie E. Moffitt, Ahmad R. Hariri","doi":"10.1038/s43587-025-00897-z","DOIUrl":"10.1038/s43587-025-00897-z","url":null,"abstract":"To understand how aging affects functional decline and increases disease risk, it is necessary to develop measures of how fast a person is aging. Using data from the Dunedin Study, we introduce an accurate and reliable measure for the rate of longitudinal aging derived from cross-sectional brain magnetic resonance imaging, that is, the Dunedin Pace of Aging Calculated from NeuroImaging (DunedinPACNI). Exporting this measure to the Alzheimer’s Disease Neuroimaging Initiative, UK Biobank and BrainLat datasets revealed that faster DunedinPACNI predicted cognitive impairment, accelerated brain atrophy and conversion to diagnosed dementia. Faster DunedinPACNI also predicted physical frailty, poor health, future chronic diseases and mortality in older adults. When compared to brain age gap, DunedinPACNI was similarly or more strongly related to clinical outcomes. DunedinPACNI is a next-generation brain magnetic resonance imaging biomarker that can help researchers explore aging effects on health outcomes and evaluate the effectiveness of antiaging strategies. Differences in the Pace of Aging are important for many health outcomes but difficult to measure. Here the authors describe the Dunedin Pace of Aging Calculated from NeuroImaging measure, an approach that uses a single brain image to measure how fast a person is aging and can help predict mortality or the risk of developing chronic disease.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1619-1636"},"PeriodicalIF":19.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546703","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 : 2025-06-30DOI: 10.1038/s43587-025-00911-4
Tim J. Nonninger, Jennifer Mak, Birgit Gerisch, Valentina Ramponi, Kazuto Kawamura, Roberto Ripa, Klara Schilling, Christian Latza, Jonathan Kölschbach, Manuel Serrano, Adam Antebi
{"title":"A TFEB–TGFβ axis systemically regulates diapause, stem cell resilience and protects against a senescence-like state","authors":"Tim J. Nonninger, Jennifer Mak, Birgit Gerisch, Valentina Ramponi, Kazuto Kawamura, Roberto Ripa, Klara Schilling, Christian Latza, Jonathan Kölschbach, Manuel Serrano, Adam Antebi","doi":"10.1038/s43587-025-00911-4","DOIUrl":"10.1038/s43587-025-00911-4","url":null,"abstract":"Diapause is a long-lived state of resilience that allows organisms to outlast adversity. Caenorhabditis elegans can endure months in a fasting-induced adult reproductive diapause (ARD) and, upon refeeding, regenerate and reproduce. Here we find that mutants of ARD master regulator hlh-30/TFEB arrest in a senescence-like state during ARD and refeeding, in which germline stem cells are characterized by DNA damage, nucleolar expansion, cell cycle arrest and mitochondrial dysfunction, alongside dysregulated immune and growth metabolic signatures, elevated senescence-associated β-galactosidase and premature aging at the organismal level. Forward genetic screens reveal a TFEB–TGFβ signaling axis that systemically controls diapause, stem cell longevity and senescence, aligning nutrient supply to proper metabolism and growth signaling. Notably, TFEB’s vital role is conserved in mouse embryonic and human cancer diapause. Thus, ARD offers a powerful model to study stem cell longevity and senescence in vivo, directly relevant to mammals. Nonninger et al. identify the TFEB–TGFβ signaling axis as a regulator of stem cell resilience that protects against a senescence-like state during the adult diapause in Caenorhabditis elegans, a mechanism conserved in vertebrate aging and mammalian cancer.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 7","pages":"1340-1357"},"PeriodicalIF":19.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532090","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 : 2025-06-30DOI: 10.1038/s43587-025-00902-5
Roméo S. Blanc, Nidhi Shah, Sarah Hachmer, Noah A. S. Salama, Fanju W. Meng, Alireza Mousaei, Gayatri Puri, Jeonghye Hannah Hwang, Elizabeth E. Wacker, Benjamin A. Yang, Carlos A. Aguilar, Joe V. Chakkalakal, John O. Onukwufor, Patrick J. Murphy, Laura M. Calvi, F. Jeffrey Dilworth, Robert T. Dirksen
{"title":"Epigenetic erosion of H4K20me1 induced by inflammation drives aged stem cell ferroptosis","authors":"Roméo S. Blanc, Nidhi Shah, Sarah Hachmer, Noah A. S. Salama, Fanju W. Meng, Alireza Mousaei, Gayatri Puri, Jeonghye Hannah Hwang, Elizabeth E. Wacker, Benjamin A. Yang, Carlos A. Aguilar, Joe V. Chakkalakal, John O. Onukwufor, Patrick J. Murphy, Laura M. Calvi, F. Jeffrey Dilworth, Robert T. Dirksen","doi":"10.1038/s43587-025-00902-5","DOIUrl":"10.1038/s43587-025-00902-5","url":null,"abstract":"Aging is characterized by a decline in the functionality and number of stem cells across the organism. In this study, we uncovered a mechanism by which systemic inflammation drives muscle stem cell (MuSC) aging through epigenetic erosion. We demonstrate that age-related inflammation decreases monomethylation of H4K20 in MuSCs, disrupting their quiescence and inducing ferroptosis, a form of iron-dependent cell death. Our findings show that inflammatory signals downregulate Kmt5a, the enzyme responsible for depositing H4K20me1, leading to the epigenetic silencing of anti-ferroptosis genes. This results in aberrant iron metabolism, increased reactive oxygen species levels and lipid peroxidation in aged MuSCs. Notably, long-term inhibition of systemic inflammation that is initiated at 12 months of age effectively prevents ferroptosis, preserves MuSC numbers and enhances muscle regeneration and functional recovery. These findings reveal an epigenetic switch that links chronic inflammation to MuSC aging and ferroptosis, offering potential therapeutic strategies for combating age-related muscle degeneration. Blanc et al. uncover how chronic inflammation triggers an epigenetic switch in aged muscle stem cells, leading to iron accumulation and cell death by ferroptosis—offering insights into muscle aging and potential paths for regenerative therapies.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1491-1509"},"PeriodicalIF":19.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532092","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 : 2025-06-30DOI: 10.1038/s43587-025-00908-z
Ninghe Sun, Chun-Hsin Lin, Michelle Y. Li, Yuting Wang, Danyang Chen, Xiangle Ren, Feng Zhang, Yi Zhang
{"title":"Clusterin drives myeloid bias in aged hematopoietic stem cells by regulating mitochondrial function","authors":"Ninghe Sun, Chun-Hsin Lin, Michelle Y. Li, Yuting Wang, Danyang Chen, Xiangle Ren, Feng Zhang, Yi Zhang","doi":"10.1038/s43587-025-00908-z","DOIUrl":"10.1038/s43587-025-00908-z","url":null,"abstract":"Aged hematopoietic stem cells (HSCs) exhibit diminished self-renewal and myeloid-biased differentiation with a decline in hematopoiesis and adaptive immune function. However, the molecular regulation of this impaired function remains largely unknown. Here, through an in vivo CRISPR–Cas9-based screen, we uncovered clusterin (Clu) as a driver of biased differentiation. Clu is upregulated in aged HSCs, and its knockout diminishes biased differentiation. Clu promotes mitochondrial hyperfusion by interacting with Mfn2 in aged HSCs, and its ablation attenuates oxidative phosphorylation, improves mitophagy, and reverses myeloid-biased differentiation via the OXPHOS-p38-Cebpb axis. Transplantation of Clu-depleted aged HSCs into middle-aged mice results in balanced hematopoiesis and improved physical functions. Together, our data identify Clu as a critical regulator of aging-associated myeloid bias and reveal an Mfn2-OXPHOS-p38-Cebpb axis as the mechanism underlying how Clu upregulation in aged HSCs leads to myeloid-biased differentiation, providing a target for rejuvenation of aged hematopoietic and immune systems. Performing a CRISPR–Cas9 screen in aged mice, Sun and colleagues identify clusterin as a driver of myeloid-biased hematopoietic stem cell differentiation in aging, through regulation of mitochondrial function via a Mnf2-OXPHOS-p38-Cebpb regulatory axis.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 8","pages":"1510-1527"},"PeriodicalIF":19.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532091","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
