# DNAmFitAge: biological age indicator incorporating physical fitness

## TL;DR

This paper introduces DNAmFitAge, a new biological age indicator that incorporates physical fitness measures into DNA methylation clocks, showing better health outcomes for fitter individuals.

## Contribution

The paper introduces DNAmFitAge, a novel biological age indicator that integrates physical fitness parameters into DNA methylation data.

## Key findings

- DNAmFitAge is associated with low-intermediate physical activity levels (p = 6.4E-13) and correlates with stronger fitness parameters in both males and females.
- Male body builders have a significantly lower DNAmFitAge and higher DNAmVO2max compared to controls (p = 0.046 and p = 0.023 respectively).
- Physically fit individuals have a younger DNAmFitAge and experience lower mortality and disease risks.

## Abstract

Physical fitness is a well-known correlate of health and the aging process and DNA methylation (DNAm) data can capture aging via epigenetic clocks. However, current epigenetic clocks did not yet use measures of mobility, strength, lung, or endurance fitness in their construction. We develop blood-based DNAm biomarkers for fitness parameters gait speed (walking speed), maximum handgrip strength, forced expiratory volume in one second (FEV1), and maximal oxygen uptake (VO2max) which have modest correlation with fitness parameters in five large-scale validation datasets (average r between 0.16–0.48). We then use these DNAm fitness parameter biomarkers with DNAmGrimAge, a DNAm mortality risk estimate, to construct DNAmFitAge, a new biological age indicator that incorporates physical fitness. DNAmFitAge is associated with low-intermediate physical activity levels across validation datasets (p = 6.4E-13), and younger/fitter DNAmFitAge corresponds to stronger DNAm fitness parameters in both males and females. DNAmFitAge is lower (p = 0.046) and DNAmVO2max is higher (p = 0.023) in male body builders compared to controls. Physically fit people have a younger DNAmFitAge and experience better age-related outcomes: lower mortality risk (p = 7.2E-51), coronary heart disease risk (p = 2.6E-8), and increased disease-free status (p = 1.1E-7). These new DNAm biomarkers provide researchers a new method to incorporate physical fitness into epigenetic clocks.