Ludger J.E. Goeminne, Anastasiya Vladimirova, Alec Eames, Alexander Tyshkovskiy, M. Austin Argentieri, Kejun Ying, Mahdi Moqri, Vadim N. Gladyshev
{"title":"Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systems","authors":"Ludger J.E. Goeminne, Anastasiya Vladimirova, Alec Eames, Alexander Tyshkovskiy, M. Austin Argentieri, Kejun Ying, Mahdi Moqri, Vadim N. Gladyshev","doi":"10.1016/j.cmet.2024.10.005","DOIUrl":null,"url":null,"abstract":"Aging is a complex process manifesting at molecular, cellular, organ, and organismal levels. It leads to functional decline, disease, and ultimately death, but the relationship between these fundamental biomedical features remains elusive. By applying elastic net regularization to plasma proteome data of over 50,000 human subjects in the UK Biobank and other cohorts, we report interpretable organ-specific and conventional aging models trained on chronological age, mortality, and longitudinal proteome data. These models predict organ/system-specific disease and indicate that men age faster than women in most organs. Accelerated organ aging leads to diseases in these organs, and specific diets, lifestyles, professions, and medications influence organ aging rates. We then identify proteins driving these associations with organ-specific aging. Our analyses reveal that age-related chronic diseases epitomize accelerated organ- and system-specific aging, modifiable through environmental factors, advocating for both universal whole-organism and personalized organ/system-specific anti-aging interventions.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"126 1","pages":""},"PeriodicalIF":27.7000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell metabolism","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cmet.2024.10.005","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Aging is a complex process manifesting at molecular, cellular, organ, and organismal levels. It leads to functional decline, disease, and ultimately death, but the relationship between these fundamental biomedical features remains elusive. By applying elastic net regularization to plasma proteome data of over 50,000 human subjects in the UK Biobank and other cohorts, we report interpretable organ-specific and conventional aging models trained on chronological age, mortality, and longitudinal proteome data. These models predict organ/system-specific disease and indicate that men age faster than women in most organs. Accelerated organ aging leads to diseases in these organs, and specific diets, lifestyles, professions, and medications influence organ aging rates. We then identify proteins driving these associations with organ-specific aging. Our analyses reveal that age-related chronic diseases epitomize accelerated organ- and system-specific aging, modifiable through environmental factors, advocating for both universal whole-organism and personalized organ/system-specific anti-aging interventions.
期刊介绍:
Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others.
Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.