The role of epigenetic age acceleration and social disadvantage in cardiometabolic health in southeast Louisiana women.

<h4>Background</h4>Cardiometabolic risk factors can disrupt DNA methylation (DNAm) patterns, accelerate cellular aging, and contribute to age-related disorders, including cardiovascular disease (CVD) and diabetes. Social disadvantage may exacerbate these biological processes, yet its relationship with epigenetic aging and cardiometabolic disease across time remains incompletely understood. We examined associations between epigenetic age acceleration and both social disadvantage and cardiometabolic diseases. We assessed whether these associations differed in each study wave.<h4>Results</h4>Participants were drawn from The Women and Their Children's Health (WaTCH) cohort and assessed at Wave 1 (2012-2014; N = 865) and Wave 3 (2023-2025; N = 348). At Wave 1, participants had a mean age of 46.9 ± 11.9 years and identified as Black (38.0%) or White (56.2%). Social disadvantage was assessed using an individual-level socioeconomic status (SES) index (education, income, and health insurance) and the Area Deprivation Index (ADI). DNAm was measured from blood samples to derive epigenetic age acceleration metrics (GrimAge2, PhenoAge, and DunedinPACE). Lower SES index and higher ADI were associated with greater epigenetic age acceleration and a faster pace of aging. CVD (45.2%) and diabetes (15.6%) at Wave 1 were more prevalent among participants with lower SES index, higher ADI, Black race, and higher body mass index (BMI). After adjustment for BMI, alcohol use, ADI, SES, smoking, and cell composition, both CVD and diabetes were associated with higher GrimAge2 and PhenoAge acceleration and a faster pace of aging at Wave 1. At Wave 3, diabetes was associated with all measures of epigenetic age acceleration after covariate adjustment.<h4>Conclusions</h4>CVD and diabetes were more common among socially disadvantaged women and were associated with accelerated epigenetic aging. These findings highlight the biological correlates of social disadvantage and underscore the need for targeted public health interventions addressing social drivers of health to mitigate cardiometabolic disease risk.