Ammous Farah, Peterson Mark D, Mitchell Colter, Faul Jessica D
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA.
Department of Physical Medicine and Rehabilitation, University of Michigan Medicine, Ann Arbor, Michigan, USA.
J Cachexia Sarcopenia Muscle. 2025 Jun;16(3):e13873. doi: 10.1002/jcsm.13873.
Epigenetic aging measures or clocks are DNA methylation-based indicators of biological aging, linked to health outcomes and disease risk. Physical activity and exercise may influence epigenetic aging, suggesting a pathway through which it promotes healthier aging and reduces chronic disease burden. In this study, we assessed the association between self-reported moderate-to-vigorous physical activity and epigenetic age acceleration (EAA) in participants of the Health and Retirement Study, followed biennially for 12 years from 2004 to 2016.
Leukocyte DNA methylation was measured from venous blood samples collected in 2016 and second-generation epigenetic clocks (GrimAge, PhenoAge and DunedinPACE) were used to assess EAA. Physical activity was assessed at each wave, with participants reporting vigorous activity at least once per week or moderate activity more than once per week or more categorized as 'physically active'. We used weighted linear regression models for cross-sectional analysis in 2016. Additionally, we used a structured life-course modelling approach (SLCMA) to assess how the timing of physical activity is associated with EAA, testing both wave-specific physical activity measures and an accumulation measure indicative of sustained physical activity over the follow-up period.
In 2016, 58% of the participants were classified as physically active. In cross-sectional analysis, physically active participants had lower EAA than inactive participants: -1.26 (95% confidence interval (CI): -1.59, -0.93) years for GrimAge acceleration, -1.70 (95% CI: -2.26, -1.15) for PhenoAge acceleration and -0.05 (95% CI: -0.06, -0.04) years per chronological year for DunedinPACE, adjusted for age, gender, race/ethnicity, education, total wealth and current smoking status. The associations attenuated slightly but remained significant after further adjusting for body mass index, mobility limitations and chronic disease diagnosis. We found evidence of effect modification in the association between physical activity and EAA by social factors, with stronger associations in males compared to females for DunedinPACE (P = 0.04) and a positive association between physical activity and increased EAA among Hispanics compared to non-Hispanic Whites for GrimAge (P = 0.009). Our longitudinal analysis using SLCMA identified both accumulation and most recent physical activity in 2016 as the strongest predictors of EAA.
Our findings highlight physical activity as a robust factor associated with slower epigenetic aging, with both accumulation and concurrent physical activity as the strongest predictors. These results underscore the role of physical activity in promoting healthier biological aging, suggesting its potential as a target for interventions aimed at mitigating age-related health decline.
表观遗传衰老指标或时钟是基于DNA甲基化的生物衰老指标，与健康结果和疾病风险相关。身体活动和锻炼可能会影响表观遗传衰老，这表明存在一条促进更健康衰老和减轻慢性病负担的途径。在本研究中，我们评估了健康与退休研究参与者自我报告的中度至剧烈身体活动与表观遗传年龄加速（EAA）之间的关联，该研究从2004年至2016年每两年进行一次，为期12年。
从2016年采集的静脉血样本中测量白细胞DNA甲基化，并使用第二代表观遗传时钟（GrimAge、PhenoAge和达尼丁PACE）评估EAA。在每次随访时评估身体活动情况，参与者报告每周至少进行一次剧烈活动或每周进行多次中度活动或更多活动被归类为“身体活跃”。我们使用加权线性回归模型对2016年的数据进行横断面分析。此外，我们使用结构化生命历程建模方法（SLCMA）来评估身体活动的时间与EAA之间的关联，同时测试特定随访波次的身体活动指标以及一个表示随访期间持续身体活动的累积指标。
2016年，58%的参与者被归类为身体活跃。在横断面分析中，身体活跃的参与者的EAA低于不活跃的参与者：GrimAge加速为-1.26（95%置信区间（CI）：-1.59，-0.93）年，PhenoAge加速为-1.70（95%CI：-2.26，-1.15），达尼丁PACE每实际年龄年为-0.05（95%CI：-0.06，-0.04）年，对年龄、性别、种族/族裔、教育程度、总财富和当前吸烟状况进行了调整。在进一步调整体重指数、行动能力限制和慢性病诊断后，这些关联略有减弱但仍具有统计学意义。我们发现社会因素对身体活动与EAA之间的关联存在效应修饰，对于达尼丁PACE，男性的关联比女性更强（P = 0.04），对于GrimAge，西班牙裔与非西班牙裔白人相比，身体活动与EAA增加之间存在正相关（P = 0.009）。我们使用SLCMA进行的纵向分析确定2016年的累积身体活动和最近的身体活动是EAA的最强预测因素。
我们的研究结果强调身体活动是与表观遗传衰老减缓相关的一个重要因素，累积身体活动和当前身体活动都是最强的预测因素。这些结果强调了身体活动在促进更健康的生物衰老中的作用，表明其作为旨在减轻与年龄相关的健康衰退的干预目标的潜力。
