DNAmFitAge: Biological Age Indicator Incorporating Physical Fitness

Physical fitness is a well-known correlate of health and the aging process. DNA methylation (DNAm) data lend themselves for estimating chronological and biological age through epigenetic clocks. However, current epigenetic clocks did not yet use measures of mobility, strength, lung, or endurance physical fitness parameters in their construction. Here, we develop blood DNAm biomarkers for fitness parameters gait speed (walking speed), hand grip strength, forced expiratory volume in one second (FEV1), and maximal oxygen uptake (VO2max). We then use these DNAm biomarkers to construct DNAmFitAge, a new biological age indicator that incorporates physical fitness with epigenetic mortality risk estimators. Adjusting DNAmFitAge for chronological age generates a novel measure of epigenetic age acceleration, FitAgeAcceleration, which is informative for physical activity level (p=1.2E-12), mortality risk (p=5.9E-13), coronary heart disease risk (p=0.0051), comorbidities (p=9.0E-9), and disease-free status (p=1.1E-6) across several large validation datasets. These newly constructed DNAm biomarkers and DNAmFitAge provide researchers and physicians a new method to incorporate physical fitness into epigenetic clocks and emphasizes the effect of lifestyle on the aging process.