Am J Epidemiol. 2021 Jun 1;190(6):984-993. doi: 10.1093/aje/kwaa251.
Epigenetic clocks use DNA methylation to estimate biological age. Whether body composition and physical activity are associated with these clocks is not well understood. Using blood samples collected at enrollment (2003-2009) from 2,758 women in the US nationwide Sister Study, we calculated 6 epigenetic age acceleration metrics using 4 epigenetic clocks (Hannum, Horvath, PhenoAge, GrimAge). Recreational physical activity was self-reported, and adiposity measures were assessed by trained medical examiners (body mass index (BMI), waist-to-hip ratio (WtH), waist circumference). In cross-sectional analyses, all adiposity measures were associated with epigenetic age acceleration. The strongest association was for BMI and PhenoAge, a measure of biological age that correlates with chronic disease (BMI of ≥35.0 vs. 18.5-24.9, β = 3.15 years, 95% confidence interval (CI): 2.41, 3.90; P for trend < 0.001). In a mutual-adjustment model, both were associated with PhenoAge age acceleration (BMI of ≥35.0 vs. 18.5-24.9, β = 2.69 years, 95% CI: 1.90, 3.48; P for trend < 0.001; quartile 4 vs.1 WtH, β = 1.00 years, 95% CI: 0.34, 1.65; P for trend < 0.008). After adjustment, physical activity was associated only with GrimAge (quartile 4 vs. 1, β = -0.42 years, 95% CI: -0.70, -0.14; P for trend = 0.001). Physical activity attenuated the waist circumference associations with PhenoAge and GrimAge. Excess adiposity was associated with epigenetic age acceleration; physical activity might attenuate associations with waist circumference.
表观遗传时钟利用 DNA 甲基化来估计生物年龄。目前人们对于身体成分和身体活动与这些时钟之间的关系还不是很了解。本研究使用美国全国范围内姐妹研究（Sister Study）中 2758 名女性在招募时（2003-2009 年）采集的血液样本，使用 4 种表观遗传时钟（Hannum、Horvath、PhenoAge 和 GrimAge）计算了 6 种表观遗传年龄加速指标。通过经过培训的医疗检查人员评估了身体活动的情况（身体质量指数（BMI）、腰臀比（WtH）、腰围）和身体肥胖程度。在横断面分析中，所有肥胖指标均与表观遗传年龄加速有关。与慢性疾病相关性最强的是 BMI 和 PhenoAge，这是一种衡量生物年龄的指标（BMI≥35.0 与 18.5-24.9，β=3.15 岁，95%置信区间（CI）：2.41，3.90；P 趋势<0.001）。在相互调整模型中，两者均与 PhenoAge 年龄加速有关（BMI≥35.0 与 18.5-24.9，β=2.69 岁，95%CI：1.90，3.48；P 趋势<0.001；四分位距 4 与 1 WtH，β=1.00 岁，95%CI：0.34，1.65；P 趋势<0.008）。调整后，仅发现身体活动与 GrimAge 相关（四分位距 4 与 1，β=-0.42 岁，95%CI：-0.70，-0.14；P 趋势=0.001）。身体活动减弱了腰围与 PhenoAge 和 GrimAge 的关联。身体肥胖与表观遗传年龄加速有关；身体活动可能会减弱与腰围的关联。
