Nature aging最新文献

{"title":"Pharmacological TERT activation attenuates phenotypes of natural aging","authors":"Hannah Walters","doi":"10.1038/s43587-024-00673-5","DOIUrl":"10.1038/s43587-024-00673-5","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 7","pages":"904-904"},"PeriodicalIF":17.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560659","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":"Immune-checkpoint blockade protects aged mice from infection","authors":"Daniel Thiele, Nicole L. La Gruta","doi":"10.1038/s43587-024-00664-6","DOIUrl":"10.1038/s43587-024-00664-6","url":null,"abstract":"A study demonstrates the efficacy of immune-checkpoint blockade in prolonging survival and boosting CD8+ T cell function in aged mice after pathogen exposure. These findings highlight how aging-related immune changes may lead to augmented CD8+ T cell responses to checkpoint blockade, which results in improved protection from infection. The findings also highlight the importance of understanding immune aging in future efforts to target immunotherapies to older adults.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 7","pages":"907-908"},"PeriodicalIF":17.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560658","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":"A deep learning model accurately predicts 1-year mortality but at the risk of unfairness","authors":"","doi":"10.1038/s43587-024-00665-5","DOIUrl":"10.1038/s43587-024-00665-5","url":null,"abstract":"A deep learning model accurately predicts 1-year mortality for the entire Finnish population. Despite robust performance and potential as a digital marker of aging, fairness analyses reveal prediction disparities, so integration into public health should be approached cautiously.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 7","pages":"913-914"},"PeriodicalIF":17.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494655","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":"Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice","authors":"Sara Zumerle, Miles Sarill, Miriam Saponaro, Manuel Colucci, Liliana Contu, Edoardo Lazzarini, Roberta Sartori, Camilla Pezzini, Anna Rinaldi, Anna Scanu, Jacopo Sgrignani, Patrizia Locatelli, Marianna Sabbadin, Aurora Valdata, Daniela Brina, Isabella Giacomini, Beatrice Rizzo, Alessandra Pierantoni, Saman Sharifi, Silvia Bressan, Claudia Altomare, Yulia Goshovska, Chiara Giraudo, Roberto Luisetto, Luca Iaccarino, Cristina Torcasio, Simone Mosole, Emiliano Pasquini, Andrea Rinaldi, Laura Pellegrini, Gregorio Peron, Matteo Fassan, Stefano Masiero, Andrea Maria Giori, Stefano Dall’Acqua, Johan Auwerx, Pietro Cippà, Andrea Cavalli, Marco Bolis, Marco Sandri, Lucio Barile, Monica Montopoli, Andrea Alimonti","doi":"10.1038/s43587-024-00663-7","DOIUrl":"10.1038/s43587-024-00663-7","url":null,"abstract":"Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16LUC reporter mice. We profiled the constituent components of HK by mass spectrometry, and identified luteolin—the most concentrated flavonoid in HK—as a senomorphic compound. Mechanistically, by performing surface plasmon resonance and in situ proximity ligation assay, we found that luteolin disrupted the p16–CDK6 interaction. This work demonstrates that administration of HK promotes longevity in mice, possibly by modulating cellular senescence and by disrupting the p16–CDK6 interaction. Botanical extracts offer a valuable resource for identifying therapies. Zumerle, Sarill et al. show that a standardized extract of Salvia haenkei extends lifespan and healthspan in naturally aged mice by modulating inflammation and cellular senescence, and identify the constituent component luteolin as a senomorphic that disrupts the p16–CDK6 interaction.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1231-1248"},"PeriodicalIF":17.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00663-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478273","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":"The genetic architecture of biological age in nine human organ systems","authors":"Junhao Wen, Ye Ella Tian, Ioanna Skampardoni, Zhijian Yang, Yuhan Cui, Filippos Anagnostakis, Elizabeth Mamourian, Bingxin Zhao, Arthur W. Toga, Andrew Zalesky, Christos Davatzikos","doi":"10.1038/s43587-024-00662-8","DOIUrl":"10.1038/s43587-024-00662-8","url":null,"abstract":"Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we characterize the genetic architecture of the biological age gap (BAG; the difference between machine learning-predicted age and chronological age) across nine human organ systems in 377,028 participants of European ancestry from the UK Biobank. The BAGs were computed using cross-validated support vector machines, incorporating imaging, physical traits and physiological measures. We identify 393 genomic loci–BAG pairs (P < 5 × 10–8) linked to the brain, eye, cardiovascular, hepatic, immune, metabolic, musculoskeletal, pulmonary and renal systems. Genetic variants associated with the nine BAGs are predominantly specific to the respective organ system (organ specificity) while exerting pleiotropic links with other organ systems (interorgan cross-talk). We find that genetic correlation between the nine BAGs mirrors their phenotypic correlation. Further, a multiorgan causal network established from two-sample Mendelian randomization and latent causal variance models revealed potential causality between chronic diseases (for example, Alzheimer’s disease and diabetes), modifiable lifestyle factors (for example, sleep duration and body weight) and multiple BAGs. Our results illustrate the potential for improving human organ health via a multiorgan network, including lifestyle interventions and drug repurposing strategies. Using machine learning techniques applied to multimodal UK Biobank data, Wen et al. characterize the genetic basis of the biological age gaps of individual organs, uncovering interorgan cross-talk and links between chronic diseases, lifestyle factors and biological age gaps.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1290-1307"},"PeriodicalIF":17.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474153","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":"Adherence to the planetary health diet and cognitive decline: findings from the ELSA-Brasil study","authors":"Natalia Gomes Gonçalves, Leandro Teixeira Cacau, Naomi Vidal Ferreira, Paulo Andrade Lotufo, Alessandra Carvalho Goulart, Maria Carmen Viana, Sandhi Maria Barreto, Isabela Martins Bensenor, Dirce Maria Marchioni, Claudia Kimie Suemoto","doi":"10.1038/s43587-024-00666-4","DOIUrl":"10.1038/s43587-024-00666-4","url":null,"abstract":"The EAT–Lancet Commission proposed a planetary health diet to improve human health within planetary boundaries; however, little is known about the association between adherence to this diet and cognitive decline. We used data from three waves of the Brazilian Longitudinal Study of Adult Health to evaluate the association between the planetary health diet and cognitive decline using linear mixed-effects models. Here we show that in 11,737 participants (mean (s.d.) age 51.6 (9.0) years, 54% women and 53% white), higher adherence to the planetary health diet was associated with slower memory decline (P = 0.046) and that income was a modifier in this association (P < 0.001). Adherence to the planetary health diet was associated with slower decline of memory (P = 0.040) and global cognition (P = 0.009) in high-income participants. No association was found among low-income participants. The results of our study highlight that the promotion of healthy dietary patterns should take into consideration income barriers as well as differences in dietary habits to achieve high adherence. Using longitudinal data from the ELSA-Brasil study, Gonçalves et al. report that income is a barrier to how adherence to the sustainable planetary health diet is linked to slower cognitive decline.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1465-1476"},"PeriodicalIF":17.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474152","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":"Ferroptotic stress drives liver aging and metabolic dysfunction","authors":"","doi":"10.1038/s43587-024-00654-8","DOIUrl":"10.1038/s43587-024-00654-8","url":null,"abstract":"Older age is associated with metabolic stress and increases the risk of degeneration of organs that maintain metabolic homeostasis, including the liver. We discovered that aging promotes ferroptosis in hepatocytes, that ferroptotic stress is generally increased in degenerating organs, and that reducing ferroptosis reverses aging-related metabolic dysfunction and liver damage.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 7","pages":"911-912"},"PeriodicalIF":17.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461445","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":"Aging promotes metabolic dysfunction-associated steatotic liver disease by inducing ferroptotic stress","authors":"Kuo Du, Liuyang Wang, Ji Hye Jun, Rajesh K. Dutta, Raquel Maeso-Díaz, Seh Hoon Oh, Dennis C. Ko, Anna Mae Diehl","doi":"10.1038/s43587-024-00652-w","DOIUrl":"10.1038/s43587-024-00652-w","url":null,"abstract":"Susceptibility to the biological consequences of aging varies among organs and individuals. We analyzed hepatocyte transcriptomes of healthy young and aged male mice to generate an aging hepatocyte gene signature, used it to deconvolute transcriptomic data from humans and mice with metabolic dysfunction-associated liver disease, validated findings with functional studies in mice and applied the signature to transcriptomic data from other organs to determine whether aging-sensitive degenerative mechanisms are conserved. We discovered that the signature enriches in diseased livers in parallel with degeneration. It is also enriched in failing human hearts, diseased kidneys and pancreatic islets from individuals with diabetes. The signature includes genes that control ferroptosis. Aged mice develop more hepatocyte ferroptosis and liver degeneration than young mice when fed diets that induce metabolic stress. Inhibiting ferroptosis shifts the liver transcriptome of old mice toward that of young mice and reverses aging-exacerbated liver damage, identifying ferroptosis as a tractable, conserved mechanism for aging-related tissue degeneration. The mechanisms underlying susceptibility to metabolic dysfunction-associated steatotic liver disease (MASLD) in aging are incompletely understood. Here the authors show that an aging hepatocyte gene signature is enriched in MASLD liver tissue and contains ferroptosis genes. Experiments in mice show that metabolic stress increases ferroptosis in liver tissue in old compared to young animals and that blocking ferroptosis in old animals reduces the susceptibility to metabolic stress.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 7","pages":"949-968"},"PeriodicalIF":17.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452543","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":"Age differentially impacts adaptive immune responses induced by adenoviral versus mRNA vaccines against COVID-19","authors":"Beatrice Dallan, Davide Proietto, Martina De Laurentis, Eleonora Gallerani, Mara Martino, Sara Ghisellini, Amedeo Zurlo, Stefano Volpato, Benedetta Govoni, Michela Borghesi, Valentina Albanese, Victor Appay, Stefano Bonnini, Sian Llewellyn-Lacey, Salvatore Pacifico, Laura Grumiro, Martina Brandolini, Simona Semprini, Vittorio Sambri, Kristin Ladell, Helen M. Parry, Paul A. H. Moss, David A. Price, RIV Study Group, Antonella Caputo, Riccardo Gavioli, Francesco Nicoli","doi":"10.1038/s43587-024-00644-w","DOIUrl":"10.1038/s43587-024-00644-w","url":null,"abstract":"Adenoviral and mRNA vaccines encoding the viral spike (S) protein have been deployed globally to contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Older individuals are particularly vulnerable to severe infection, probably reflecting age-related changes in the immune system, which can also compromise vaccine efficacy. It is nonetheless unclear to what extent different vaccine platforms are impacted by immunosenescence. Here, we evaluated S protein-specific immune responses elicited by vaccination with two doses of BNT162b2 or ChAdOx1-S and subsequently boosted with a single dose of BNT162b2 or mRNA-1273, comparing age-stratified participants with no evidence of previous infection with SARS-CoV-2. We found that aging profoundly compromised S protein-specific IgG titers and further limited S protein-specific CD4+ and CD8+ T cell immunity as a probable function of progressive erosion of the naive lymphocyte pool in individuals vaccinated initially with BNT162b2. Our results demonstrate that primary vaccination with ChAdOx1-S and subsequent boosting with BNT162b2 or mRNA-1273 promotes sustained immunological memory in older adults and potentially confers optimal protection against coronavirus disease 2019. Age-related immune dysfunction can compromise immune responses to infection and vaccine efficacy. Across two cohorts, Dallan et al. demonstrate that protective immunity against severe acute respiratory syndrome coronavirus is optimally maintained in older adults after primary adenoviral immunization (ChAdOx1-S) and subsequent mRNA vaccine boosting (BNT162b2 or mRNA-1273).","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 8","pages":"1121-1136"},"PeriodicalIF":17.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452542","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":"Deep learning-based prediction of one-year mortality in Finland is an accurate but unfair aging marker","authors":"Andrius Vabalas, Tuomo Hartonen, Pekka Vartiainen, Sakari Jukarainen, Essi Viippola, Rodosthenis S. Rodosthenous, Aoxing Liu, Sara Hägg, Markus Perola, Andrea Ganna","doi":"10.1038/s43587-024-00657-5","DOIUrl":"10.1038/s43587-024-00657-5","url":null,"abstract":"Short-term mortality risk, which is indicative of individual frailty, serves as a marker for aging. Previous age clocks focused on predicting either chronological age or longer-term mortality. Aging clocks predicting short-term mortality are lacking and their algorithmic fairness remains unexamined. We developed a deep learning model to predict 1-year mortality using nationwide longitudinal data from the Finnish population (FinRegistry; n = 5.4 million), incorporating more than 8,000 features spanning up to 50 years. We achieved an area under the curve (AUC) of 0.944, outperforming a baseline model that included only age and sex (AUC = 0.897). The model generalized well to different causes of death (AUC > 0.800 for 45 of 50 causes), including coronavirus disease 2019, which was absent in the training data. Performance varied among demographics, with young females exhibiting the best and older males the worst results. Extensive prediction fairness analyses highlighted disparities among disadvantaged groups, posing challenges to equitable integration into public health interventions. Our model accurately identified short-term mortality risk, potentially serving as a population-wide aging marker. Here the authors show that deep learning accurately predicts one-year mortality using nationwide Finnish data. Despite robust performance and potential as an aging marker, fairness analyses reveal prediction disparities, urging cautious integration into public health.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 7","pages":"1014-1027"},"PeriodicalIF":17.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00657-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447922","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}