Articles

<b>Background</b><b>: </b>Epigenetic aging, measured through various DNA methylation-based clocks, may have implications for predicting disease risk. However, the sensitivity of different epigenetic clocks that have emerged as biomarkers for biological aging and in predicting physical and mental health outcomes remains uncertain. This study examines the age and sex-adjusted associations between multiple epigenetic age acceleration measures and three key health indicators, including self-rated health, depressive symptoms, and body mass index (BMI), in a nationally representative sample of U.S. middle-aged and older adults. <b>Methods</b><b>: </b>We analyzed data from 4,018 adults in the 2016 wave of the Health and Retirement Study (HRS), which included several epigenetic age acceleration measures: HORVATH, HANNUM, LEVINE, HORVATHSKIN, LIN, WEIDNER, VIDALBRALO, YANG, ZHANG, BOCKLANDT, GARAGNANI, and GRIMAGE. Linear regression models were used to assess the associations between epigenetic age acceleration and self-rated health (poor health), depressive symptoms, and BMI, adjusting for age and sex. <b>Results</b><b>: </b>We found significant positive associations between epigenetic age acceleration and worse self-rated health, higher depressive symptoms, and increased BMI. However, these associations varied across different epigenetic clocks, with some measures potentially having more consistent utility for specific health outcomes than others. <b>Conclusion</b><b>: </b>Epigenetic age acceleration is linked to poorer self-rated health, greater depressive symptoms, and higher BMI, but choosing which epigenetic clock(s) to use is also important. These findings underscore the need to consider multiple epigenetic aging markers when assessing health risks and highlight the potential for particular clocks to serve as more sensitive indicators of physical and mental health outcomes.

Background:</b> Early life socioeconomic conditions and race/ethnicity are critical determinants of long-term health and behavioral outcomes. Epigenetic changes, particularly those measured by the GrimAge biomarker, may mediate the impact of these early adversities on later life outcomes. This study investigates the relationships between race/ethnicity, poverty at birth, epigenetic aging at age 15, and subsequent self-rated health, school discipline, depression, and school dropout at age 22. We explored sex differences in these paths. <b>Methods:</b> Data were drawn from the Fragile Families and Child Wellbeing Study (FFCWS), which included 733 youth with comprehensive follow-up data up to age 22. Structural Equation Modeling (SEM) was employed to assess the pathways from race/ethnicity and poverty at birth to epigenetic aging (GrimAge) at age 15, and subsequently to self-rated health and school discipline at age 22. The model controlled for potential confounders including sex, family structure, and parental education. <b>Results:</b> Race/ethnicity and poverty at birth were significantly associated with higher GrimAge scores at age 15 (p < 0.05). Higher GrimAge scores were predictive of poorer self-rated health (β = -0.08, p < 0.05) and increased instances of school discipline (β = 0.13, p < 0.01) at age 22. The indirect effects of race/ethnicity and poverty at birth on self-rated health and school discipline through GrimAge were also significant (p < 0.05), suggesting that epigenetic aging partially mediates these relationships. Sex differences were also observed. Poverty at birth predicted faster epigenetic aging at age 15 for males not females. We also observed that faster epigenetic aging at age 15 was predictive of school discipline of male not female participants at age 22. In contrast, faster epigenetic aging at age 15 was predictive of self-rated health (SRH) of female not male participants at age 22. <b>Conclusions:</b> This study provides evidence that with some sex differences, race/ethnicity and poverty at birth contribute to accelerated epigenetic aging (GrimAge) by age 15, which in turn predicts poorer self-rated health and increased school discipline issues by age 22. These findings emphasize the importance of early interventions targeting social determinants to mitigate long-term health and behavioral disparities. Addressing these early life conditions is crucial for improving health equity and outcomes in young adulthood.