Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm

eLife

Avshalom Caspi¹  Xu Gao²  Jonathan Mill³  David L Corcoran⁴  Andrea Baccarelli⁵  Karen Sugden⁶  Richie Poulton⁶  Pantel Vokonas⁷  Line JH Rasmussen⁸  Daniel W Belsky⁹  Carl F Pieper^1,10  Dayoon Kwon^1,10  William E Kraus^1,10  Joel Schwartz^1,11  Joseph A Prinz^1,11  Terrie E Moffitt^1,12  Renate Houts^1,13  Hona Lee Harrington^1,13  Eiliss Hannon^1,14  Louise Arseneault^1,14  Kim Huffman^1,15  Benjamin S Williams^1,15 

[1] Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, United States;Center for Genomic and Computational Biology, Duke University, Durham, United States;Clinical Research Centre, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark;Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, United States;Department of Psychology and Neuroscience, Duke University, Durham, United States;Duke University Center for the Study of Aging, Duke University, Durham, United States;Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, United States;Center for Genomic and Computational Biology, Duke University, Durham, United States;Department of Epidemiology, Columbia University Mailman School of Public Health, New York, United States;Department of Psychology and Neuroscience, Duke University, Durham, United States;Duke Molecular Physiology Institute, Duke University, Durham, United States;Duke University Center for the Study of Aging, Duke University, Durham, United States;Laboratory of Precision Environmental Health, Mailman School of Public Health, Columbia University, New York, United States;Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, United Kingdom;University of Exeter Medical School, College of Medicine and Health, Exeter, United Kingdom;

关键词: aging;    biological aging;    DNA methylation;    epigenetic;    human;    life-course;   

DOI  :  10.7554/eLife.54870

来源: DOAJ

【 摘 要 】

Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is sensitive to variation in pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972–1973. Rates of change in each biomarker over ages 26–38 years were composited to form a measure of aging-related decline, termed Pace-of-Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging.

【 授权许可】

Unknown