The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

作者：Riccardo E. Marioni, Sonia H Shah, Allan F. McRae, Stuart James Ritchie, Graciela Muniz Terrera, Sarah E. Harris, Jude Gibson, Paul H. Redmond, Simon R Cox, Alison Pattie, Janie Corley, Adele M. Taylor, Lee D. Murphy, John M. Starr, Steve Horvath, Peter M. Visscher, Naomi R. Wray, Ian J. Deary · 发表于：International Journal of Epidemiology · 年份：2015 · DOI：10.1093/ije/dyu277 · 被引用次数：612 · 研究领域：Epigenetics and DNA Methylation、Birth, Development, and Health、Health, Environment, Cognitive Aging

BACKGROUND: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. METHODS: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n = 920), 73 (n = 299) and 76 (n = 273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures. RESULTS: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10(-3) to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. Ther...