Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
Research Institute of Sport Science, University of Physical Education, Budapest, Hungary.
Aging (Albany NY). 2023 Feb 22;15(10):3904-3938. doi: 10.18632/aging.204538.
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 ( = 6.4E-13), and younger/fitter DNAmFitAge corresponds to stronger DNAm fitness parameters in both males and females. DNAmFitAge is lower ( = 0.046) and DNAmVO2max is higher ( = 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 ( = 7.2E-51), coronary heart disease risk ( = 2.6E-8), and increased disease-free status ( = 1.1E-7). These new DNAm biomarkers provide researchers a new method to incorporate physical fitness into epigenetic clocks.
身体健康是健康和衰老过程的已知相关因素，DNA 甲基化（DNAm）数据可以通过表观遗传钟来捕捉衰老。然而，目前的表观遗传钟在构建时尚未使用移动性、力量、肺部或耐力健康的测量值。我们开发了基于血液的 DNAm 生物标志物，用于评估步态速度（行走速度）、最大握力、一秒用力呼气容积（FEV1）和最大摄氧量（VO2max）等健康参数，这些标志物在五个大型验证数据集中与健康参数具有适度相关性（平均 r 值在 0.16-0.48 之间）。然后，我们使用这些 DNAm 健康参数生物标志物和 DNAmGrimAge（一种 DNAm 死亡率风险估计值）构建了 DNAmFitAge，这是一种新的生物年龄指标，纳入了身体的健康状况。DNAmFitAge 与验证数据集中的低-中等体力活动水平相关（ = 6.4E-13），并且在男性和女性中，更年轻/更健康的 DNAmFitAge 对应于更强的 DNAm 健康参数。与对照组相比，男性健身者的 DNAmFitAge 更低（ = 0.046），DNAmVO2max 更高（ = 0.023）。身体健康的人拥有更年轻的 DNAmFitAge，并且经历更好的与年龄相关的结果：更低的死亡率风险（ = 7.2E-51）、冠心病风险（ = 2.6E-8）和增加的无病状态（ = 1.1E-7）。这些新的 DNAm 生物标志物为研究人员提供了一种将身体的健康状况纳入表观遗传钟的新方法。
