Nature agingPub Date : 2024-09-03DOI: 10.1038/s43587-024-00706-z
{"title":"Age-associated changes in gene regulatory relationships affect basic cellular processes","authors":"","doi":"10.1038/s43587-024-00706-z","DOIUrl":"10.1038/s43587-024-00706-z","url":null,"abstract":"We quantified age-related changes in gene regulatory relationships across eight human tissues. Our results reveal that the gene–gene relationships that become stronger with age affect mostly genes that operate on the same cellular processes, whereas relationships that become weaker affect genes involved in different processes.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1348-1349"},"PeriodicalIF":17.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142249","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 : 2024-08-29DOI: 10.1038/s43587-024-00689-x
{"title":"Imaging the epigenetic landscape in single cells to study aging trajectories","authors":"","doi":"10.1038/s43587-024-00689-x","DOIUrl":"10.1038/s43587-024-00689-x","url":null,"abstract":"We developed ‘imaging-based chromatin and epigenetic age’ (ImAge), a technique that captures intrinsic age-related trajectories of the spatial organization of chromatin and epigenetic marks in single nuclei. We propose that ImAge represents a first-in-class imaging-based biomarker of aging with single-cell resolution.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1184-1185"},"PeriodicalIF":17.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116538","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 : 2024-08-29DOI: 10.1038/s43587-024-00695-z
Suchira Gallage, Elaine E. Irvine, Jose Efren Barragan Avila, Virinder Reen, Silvia M. A. Pedroni, Imanol Duran, Vikas Ranvir, Sanjay Khadayate, Joaquim Pombo, Sharon Brookes, Danijela Heide, Gopuraja Dharmalingham, Agharul I. Choudhury, Indrabahadur Singh, Nicolás Herranz, Santiago Vernia, Mathias Heikenwalder, Jesús Gil, Dominic J. Withers
{"title":"Ribosomal S6 kinase 1 regulates inflammaging via the senescence secretome","authors":"Suchira Gallage, Elaine E. Irvine, Jose Efren Barragan Avila, Virinder Reen, Silvia M. A. Pedroni, Imanol Duran, Vikas Ranvir, Sanjay Khadayate, Joaquim Pombo, Sharon Brookes, Danijela Heide, Gopuraja Dharmalingham, Agharul I. Choudhury, Indrabahadur Singh, Nicolás Herranz, Santiago Vernia, Mathias Heikenwalder, Jesús Gil, Dominic J. Withers","doi":"10.1038/s43587-024-00695-z","DOIUrl":"10.1038/s43587-024-00695-z","url":null,"abstract":"Inhibition of S6 kinase 1 (S6K1) extends lifespan and improves healthspan in mice, but the underlying mechanisms are unclear. Cellular senescence is a stable growth arrest accompanied by an inflammatory senescence-associated secretory phenotype (SASP). Cellular senescence and SASP-mediated chronic inflammation contribute to age-related pathology, but the specific role of S6K1 has not been determined. Here we show that S6K1 deletion does not reduce senescence but ameliorates inflammation in aged mouse livers. Using human and mouse models of senescence, we demonstrate that reduced inflammation is a liver-intrinsic effect associated with S6K deletion. Specifically, we show that S6K1 deletion results in reduced IRF3 activation; impaired production of cytokines, such as IL1β; and reduced immune infiltration. Using either liver-specific or myeloid-specific S6K knockout mice, we also demonstrate that reduced immune infiltration and clearance of senescent cells is a hepatocyte-intrinsic phenomenon. Overall, deletion of S6K reduces inflammation in the liver, suggesting that suppression of the inflammatory SASP by loss of S6K could underlie the beneficial effects of inhibiting this pathway on healthspan and lifespan. Inhibition of S6 kinase 1 (S6K1) extends lifespan in mice, but the underlying mechanisms are not fully understood. Here Gallage et al. show that reduction of S6K signaling diminishes inflammation in the aged mouse liver via suppression of the senescence-associated secretory phenotype.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 11","pages":"1544-1561"},"PeriodicalIF":17.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00695-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116539","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 : 2024-08-29DOI: 10.1038/s43587-024-00705-0
{"title":"The planetary health diet is associated with slower cognitive decline — but tied to income","authors":"","doi":"10.1038/s43587-024-00705-0","DOIUrl":"10.1038/s43587-024-00705-0","url":null,"abstract":"Income is a modifying factor in the association between increased adherence to the planetary health diet and slower cognitive decline observed in a sample of 11,737 Brazilian civil servants who were followed for 8 years. Thus, addressing the barriers posed by low income is vital when promoting healthy eating patterns.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1352-1353"},"PeriodicalIF":17.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116540","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 : 2024-08-29DOI: 10.1038/s43587-024-00685-1
Martin Alvarez-Kuglen, Kenta Ninomiya, Haodong Qin, Delany Rodriguez, Lorenzo Fiengo, Chen Farhy, Wei-Mien Hsu, Brian Kirk, Aaron Havas, Gen-Sheng Feng, Amanda J. Roberts, Rozalyn M. Anderson, Manuel Serrano, Peter D. Adams, Tatyana O. Sharpee, Alexey V. Terskikh
{"title":"ImAge quantitates aging and rejuvenation","authors":"Martin Alvarez-Kuglen, Kenta Ninomiya, Haodong Qin, Delany Rodriguez, Lorenzo Fiengo, Chen Farhy, Wei-Mien Hsu, Brian Kirk, Aaron Havas, Gen-Sheng Feng, Amanda J. Roberts, Rozalyn M. Anderson, Manuel Serrano, Peter D. Adams, Tatyana O. Sharpee, Alexey V. Terskikh","doi":"10.1038/s43587-024-00685-1","DOIUrl":"10.1038/s43587-024-00685-1","url":null,"abstract":"For efficient, cost-effective and personalized healthcare, biomarkers that capture aspects of functional, biological aging, thus predicting disease risk and lifespan more accurately and reliably than chronological age, are essential. We developed an imaging-based chromatin and epigenetic age (ImAge) that captures intrinsic age-related trajectories of the spatial organization of chromatin and epigenetic marks in single nuclei, in mice. We show that such trajectories readily emerge as principal changes in each individual dataset without regression on chronological age, and that ImAge can be computed using several epigenetic marks and DNA labeling. We find that interventions known to affect biological aging induce corresponding effects on ImAge, including increased ImAge upon chemotherapy treatment and decreased ImAge upon caloric restriction and partial reprogramming by transient OSKM expression in liver and skeletal muscle. Further, ImAge readouts from chronologically identical mice inversely correlated with their locomotor activity, suggesting that ImAge may capture elements of biological and functional age. In sum, we developed ImAge, an imaging-based biomarker of aging with single-cell resolution rooted in the analysis of spatial organization of epigenetic marks. Alvarez-Kuglen, Ninomiya, Qin, Rodriguez et al. demonstrate that the spatial organization of chromatin and epigenetic marks in individual nuclei follows age-related trajectories that can be captured by an imaging-based biomarker of aging (ImAge).","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1308-1327"},"PeriodicalIF":17.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116537","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 : 2024-08-28DOI: 10.1038/s43587-024-00708-x
Jhih-Rong Lin, Patrick Sin-Chan, Valerio Napolioni, Guillermo G. Torres, Joydeep Mitra, Quanwei Zhang, M. Reza Jabalameli, Zhen Wang, Nha Nguyen, Tina Gao, Regeneron Genetics Center, Matthias Laudes, Siegfried Görg, Andre Franke, Almut Nebel, Michael D. Greicius, Gil Atzmon, Kenny Ye, Vera Gorbunova, Warren C. Ladiges, Alan R. Shuldiner, Laura J. Niedernhofer, Paul D. Robbins, Sofiya Milman, Yousin Suh, Jan Vijg, Nir Barzilai, Zhengdong D. Zhang
{"title":"Author Correction: Rare genetic coding variants associated with human longevity and protection against age-related diseases","authors":"Jhih-Rong Lin, Patrick Sin-Chan, Valerio Napolioni, Guillermo G. Torres, Joydeep Mitra, Quanwei Zhang, M. Reza Jabalameli, Zhen Wang, Nha Nguyen, Tina Gao, Regeneron Genetics Center, Matthias Laudes, Siegfried Görg, Andre Franke, Almut Nebel, Michael D. Greicius, Gil Atzmon, Kenny Ye, Vera Gorbunova, Warren C. Ladiges, Alan R. Shuldiner, Laura J. Niedernhofer, Paul D. Robbins, Sofiya Milman, Yousin Suh, Jan Vijg, Nir Barzilai, Zhengdong D. Zhang","doi":"10.1038/s43587-024-00708-x","DOIUrl":"10.1038/s43587-024-00708-x","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1328-1328"},"PeriodicalIF":17.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00708-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094353","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 : 2024-08-26DOI: 10.1038/s43587-024-00703-2
Imanol Duran, Cleo L. Bishop, Jesús Gil, Ryan Wallis
{"title":"The promise of machine learning approaches to capture cellular senescence heterogeneity","authors":"Imanol Duran, Cleo L. Bishop, Jesús Gil, Ryan Wallis","doi":"10.1038/s43587-024-00703-2","DOIUrl":"10.1038/s43587-024-00703-2","url":null,"abstract":"The identification of senescent cells is a long-standing unresolved challenge, owing to their intrinsic heterogeneity and the lack of universal markers. In this Comment, we discuss the recent advent of machine-learning-based approaches to identifying senescent cells by using unbiased, multiparameter morphological assessments, and how these tools can assist future senescence research.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1167-1170"},"PeriodicalIF":17.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074872","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 : 2024-08-21DOI: 10.1038/s43587-024-00693-1
Elisabet A. Frick, Valur Emilsson, Thorarinn Jonmundsson, Anna E. Steindorsdottir, Erik C. B. Johnson, Raquel Puerta, Eric B. Dammer, Anantharaman Shantaraman, Amanda Cano, Mercè Boada, Sergi Valero, Pablo García-González, Elias F. Gudmundsson, Alexander Gudjonsson, Rebecca Pitts, Xiazi Qiu, Nancy Finkel, Joseph J. Loureiro, Anthony P. Orth, Nicholas T. Seyfried, Allan I. Levey, Agustin Ruiz, Thor Aspelund, Lori L. Jennings, Lenore J. Launer, Valborg Gudmundsdottir, Vilmundur Gudnason
{"title":"Serum proteomics reveal APOE-ε4-dependent and APOE-ε4-independent protein signatures in Alzheimer’s disease","authors":"Elisabet A. Frick, Valur Emilsson, Thorarinn Jonmundsson, Anna E. Steindorsdottir, Erik C. B. Johnson, Raquel Puerta, Eric B. Dammer, Anantharaman Shantaraman, Amanda Cano, Mercè Boada, Sergi Valero, Pablo García-González, Elias F. Gudmundsson, Alexander Gudjonsson, Rebecca Pitts, Xiazi Qiu, Nancy Finkel, Joseph J. Loureiro, Anthony P. Orth, Nicholas T. Seyfried, Allan I. Levey, Agustin Ruiz, Thor Aspelund, Lori L. Jennings, Lenore J. Launer, Valborg Gudmundsdottir, Vilmundur Gudnason","doi":"10.1038/s43587-024-00693-1","DOIUrl":"10.1038/s43587-024-00693-1","url":null,"abstract":"A deeper understanding of the molecular processes underlying late-onset Alzheimer’s disease (LOAD) could aid in biomarker and drug target discovery. Using high-throughput serum proteomics in the prospective population-based Age, Gene/Environment Susceptibility–Reykjavik Study (AGES) cohort of 5,127 older Icelandic adults (mean age, 76.6 ± 5.6 years), we identified 303 proteins associated with incident LOAD over a median follow-up of 12.8 years. Over 40% of these proteins were associated with LOAD independently of APOE-ε4 carrier status, were implicated in neuronal processes and overlapped with LOAD protein signatures in brain and cerebrospinal fluid. We identified 17 proteins whose associations with LOAD were strongly dependent on APOE-ε4 carrier status, with mostly consistent associations in cerebrospinal fluid. Remarkably, four of these proteins (TBCA, ARL2, S100A13 and IRF6) were downregulated by APOE-ε4 yet upregulated due to LOAD, a finding replicated in external cohorts and possibly reflecting a response to disease onset. These findings highlight dysregulated pathways at the preclinical stages of LOAD, including those both independent of and dependent on APOE-ε4 status. Using high-throughput proteomics in a prospective population-based study of older adults, Frick et al. identified over 300 proteins linked to incident late-onset Alzheimer’s disease, including associations dependent on or independent of APOE-ε4 status.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1446-1464"},"PeriodicalIF":17.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00693-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019980","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":"Accelerometer-derived ‘weekend warrior’ physical activity pattern and brain health","authors":"Jiahao Min, Zhi Cao, Tingshan Duan, Yaogang Wang, Chenjie Xu","doi":"10.1038/s43587-024-00688-y","DOIUrl":"10.1038/s43587-024-00688-y","url":null,"abstract":"Extensive evidence shows the beneficial effect of adhering to a regular physical activity (PA) pattern on brain health. However, whether the ‘weekend warrior’ pattern, characterized by concentrated moderate-to-vigorous PA (MVPA) over 1–2 days, is associated with brain health is unclear. Here, we perform a prospective cohort study including 75,629 participants from the UK Biobank with validated accelerometry data. Individuals were classified into three PA patterns using current guideline thresholds: inactive (<150 min week−1 of MVPA), weekend warrior (≥150 min week−1 with ≥50% of total MVPA occurring within 1–2 days) and regularly active (≥150 min week−1 but not meeting weekend warrior criteria). We find that the weekend warrior pattern is associated with similarly lower risks of dementia, stroke, Parkinson’s disease, depressive disorders and anxiety compared to a regularly active pattern. Our findings highlight the weekend warrior pattern as a potential alternative in preventive intervention strategies, particularly for those unable to maintain daily activity routines. Research suggests that exercise has a beneficial effect on brain health during aging but more information is needed. Here, the authors show, using UK Biobank data, that the ‘weekend warrior’ physical activity pattern, with concentrated exercise over 1–2 days, is similarly linked to lower risk of brain disorders compared to regular exercise.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1394-1402"},"PeriodicalIF":17.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019979","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 : 2024-08-15DOI: 10.1038/s43587-024-00691-3
Ting Du, Aditya Raghunandan, Humberto Mestre, Virginia Plá, Guojun Liu, Antonio Ladrón-de-Guevara, Evan Newbold, Paul Tobin, Daniel Gahn-Martinez, Saurav Pattanayak, Qinwen Huang, Weiguo Peng, Maiken Nedergaard, Douglas H. Kelley
{"title":"Restoration of cervical lymphatic vessel function in aging rescues cerebrospinal fluid drainage","authors":"Ting Du, Aditya Raghunandan, Humberto Mestre, Virginia Plá, Guojun Liu, Antonio Ladrón-de-Guevara, Evan Newbold, Paul Tobin, Daniel Gahn-Martinez, Saurav Pattanayak, Qinwen Huang, Weiguo Peng, Maiken Nedergaard, Douglas H. Kelley","doi":"10.1038/s43587-024-00691-3","DOIUrl":"10.1038/s43587-024-00691-3","url":null,"abstract":"Cervical lymphatic vessels (cLVs) have been shown to drain solutes and cerebrospinal fluid (CSF) from the brain. However, their hydrodynamical properties have never been evaluated in vivo. Here, we developed two-photon optical imaging with particle tracking in vivo of CSF tracers (2P-OPTIC) in superficial and deep cLVs of mice, characterizing their flow and showing that the major driver is intrinsic pumping by contraction of the lymphatic vessel wall. Moreover, contraction frequency and flow velocity were reduced in aged mice, which coincided with a reduction in smooth muscle actin expression. Slowed flow in aged mice was rescued using topical application of prostaglandin F2α, a prostanoid that increases smooth muscle contractility, which restored lymphatic function in aged mice and enhanced central nervous system clearance. We show that cLVs are important regulators of CSF drainage and that restoring their function is an effective therapy for improving clearance in aging. Cervical lymphatics drain cerebrospinal fluid and clear metabolic waste from the brain. Du et al. show using 2P-OPTIC that these are disrupted in aging due to reduced pumping. Restoring cervical lymphatic function with prostaglandin F2α rescues brain clearance.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1418-1431"},"PeriodicalIF":17.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989856","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}