Depression, Subjective Health, Obesity, and Multimorbidity are Associated with Epigenetic Age Acceleration

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.

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.

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.

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.