DNAmFitAge: biological age indicator incorporating physical fitness.
DNAmFitAge: biological age indicator incorporating physical fitness.
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DOI：
10.18632/aging.204538
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发表时间：
2023-02-22
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众所周知，身体健康与健康和衰老过程有关，DNA甲基化(DNaM)数据可以通过表观遗传时钟捕捉衰老。然而，目前的表观遗传时钟还没有在它们的构造中使用移动性、力量、肺或耐力健康的衡量标准。我们开发了基于血液的dNaM生物标记物，用于健身参数步态速度(步行速度)、最大握力、一秒用力呼气量(FEV1)和最大摄氧量(VO2max)，这些指标与五个大规模验证数据集中的健身参数(平均r在0.16-0.48之间)具有适度的相关性。然后，我们将这些dNaM健康参数生物标记物与dNaM死亡风险估计DNAmGrimAge一起构建DNAmFitAge，一种结合了身体健康的新的生物年龄指标。在验证数据集中，DNAmFitAge与中低体力活动水平相关(p=6.4E-13)，在男性和女性中，更年轻/更健康的DNAmFitAge与更强的dNaM健康参数相对应。男性健美运动员的DNAMFitage低于对照组(p=0.046)，DNAmVO2max高于对照组(p=0.023)。身体健康的人DNAmFitAge更年轻，与年龄相关的结果也更好：更低的死亡风险(p=7.2E-51)，更低的冠心病风险(p=2.6E-8)，以及更高的无病状态(p=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健康纳入表观遗传学时钟的新方法。
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.