The Socioeconomic Gradient in Epigenetic Ageing Clocks: Evidence from the Multi-Ethnic Study of Atherosclerosis and the Health and Retirement Study

Epigenetic clocks have been widely used to predict disease risk in multiple tissues or cells. Their success as a measure of biological ageing has prompted research on the connection between epigenetic pathways of ageing and the socioeconomic gradient in health and mortality. However, studies examining social correlates of epigenetic ageing have yielded inconsistent results. We conducted a comprehensive, comparative analysis of associations between various dimensions of socioeconomic status (SES) (education, income, wealth, occupation, neighbourhood environment, and childhood SES) and eight epigenetic clocks in two well-powered US ageing studies: The Multi-Ethnic Study of Atherosclerosis (MESA) (n = 1,211) and the Health and Retirement Study (HRS) (n = 4,018). In both studies, we found robust associations between SES measures in adulthood and the GrimAge and DunedinPoAm clocks (Bonferroni-corrected p-value < 0.01). In the HRS, significant associations with the Levine and Yang clocks were also evident. These associations were only partially mediated by smoking, alcohol consumption, and obesity, which suggests that differences in health behaviours alone cannot explain the SES gradient in epigenetic ageing in older adults. Further analyses revealed concurrent associations between polygenic risk for accelerated intrinsic epigenetic ageing, SES, and the Levine clock, indicating that genetic risk and social disadvantage may contribute additively to faster biological aging.

表观遗传时钟（epigenetic clocks）已被广泛用于预测多组织、多细胞的疾病风险。作为生物衰老的衡量指标，表观遗传时钟的成功应用推动了衰老表观遗传通路与健康、死亡的社会经济梯度之间关联的研究。然而，现有探究表观遗传衰老社会关联的研究却得到了不一致的结果。本研究针对两项具有充足统计效力的美国衰老队列研究——多民族动脉粥样硬化研究（Multi-Ethnic Study of Atherosclerosis, MESA，n=1211）与健康与退休研究（Health and Retirement Study, HRS，n=4018）——开展了全面的比较分析，探究社会经济地位（socioeconomic status, SES）的多个维度（包括教育水平、收入、财富、职业、社区环境以及儿童期SES）与8种表观遗传时钟之间的关联。两项队列研究均显示，成年期SES指标与GrimAge时钟及DunedinPoAm时钟之间存在显著且稳定的关联（Bonferroni校正后P值<0.01）。在HRS队列中，Levine时钟与Yang时钟同样呈现出显著关联。上述关联仅能由吸烟、饮酒与肥胖状况部分介导，这表明仅靠健康行为差异无法解释老年人群表观遗传衰老中的SES梯度。进一步分析显示，加速型内在表观遗传衰老的多基因风险、SES与Levine时钟之间存在共现关联，提示遗传风险与社会经济劣势可能以相加效应共同加速生物衰老。