CVD and diabetes were more common among socially disadvantaged women and were associated with accelerated epigenetic aging, highlighting 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.
Abstract
Background
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.
Results
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.
Conclusions
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.
Type 2 diabetes mellitus (T2DM) is an aging-related disease with greater incidence in older African Americans (AAs) than whites, but studies on racial disparity in epigenetic aging pathways are scarce; specifically, socio-biological aging processes are not well characterized. We investigated biological aging acceleration (aging accel) with development of T2DM and additionally, insulin resistance (IR) of nondiabetic women at baseline in cross-section. We estimated the extent to which social adversity explained AAs' greater aging accel and, together with accelerated aging, mediated their greater burden of glucometabolic outcomes. Clinical and social determinants of health (SDOH) variables and genome-wide DNA methylation data were extracted from the Women's Health Initiative with > 1,500 postmenopausal non-diabetic women. Diabetic outcome was followed for a mean of 19 years, and baseline IR was measured using fasting serum samples. Aging accel metrics were calculated with Levine's clock, and mediation effects of SDOH and aging accel was estimated via Multiple Mediation analyses. Greater aging accel was observed in T2DM, albeit with only univariate significance and IR and in AAs rather than whites. SDOH was associated with greater aging accel, but its impact on greater accelerated aging in AAs varied and in combination, was minimal. Although aging accel has greater influence than SDOH on the racial difference in glucometabolic outcomes, these parameters jointly mediated to only a limited extent T2DM/IR pathways by race. Our mediation findings are exploratory and hypothesis-generating and thus, our results warrant validation studies to better understand socio-glucometabolic pathways shared by epigenetic aging processes and to inform early risk stratification among at-risk older women for disease prevention and reduced racial health inequity.
An LE8-derived DNAm score was associated with lower cIMT across the life course and, to a lesser extent, across generations, suggesting that blood DNAm reflects cumulative cardiovascular health and vascular burden and may complement conventional cardiovascular risk assessment.
B. Mishra, E. Raitoharju, L.-P. LyytikaÌinen et al.· medRxiv· 0 citations
Social environments affect health and longevity, yet biological pathways remain incompletely understood. Data from Midlife in the United States (MIDUS) study were used to examine whether social experiences predicted mortality and whether effects were mediated by epigenetic aging, allostatic load, and health status. Outcomes included epigenetic clocks (e.g., GrimAgeV2), allostatic load (e.g., immune/inflammatory biomarkers), health status, and all-cause mortality. Among 1309 participants, positive social experiences (e.g., attending meetings) were associated with reduced mortality risk, epigenetic age deceleration, and better health; negative social experiences (e.g., childhood adversities) were associated with shortened survival, epigenetic age acceleration, and poorer health. Epigenetic aging partially mediated the mortality risk of positive and negative social exposures; inflammation attenuated the associations of positive social experiences and childhood adversity with mortality. Epigenetic aging appears to be an influential pathway linking social experiences to survival. Social conditions that slow biological aging and reduce inflammation offer promise as approaches to enhance longevity.
Holly G. Prigerson, Abigail J. Maciejewski, P. Maciejewski et al.· npj Aging· 0 citations
This study supports methylation risk scores as novel biomarkers of stress-related CHD and uncovers epigenetic regulation in monocytes as a potential underlying mechanism of stress-related CHD, highlighting biological pathways linking stress and disease and may promote personalized interventions in high-risk populations.
Sofia Benavides, Hazel Milla, Helena Palma-Gudiel et al.· medRxiv· 0 citations
It is found that socioeconomic adversity influences not only inflammatory pathways but also distinct biological aging processes, including metabolomic aging, and that socioeconomic adversity influences not only inflammatory pathways but also distinct biological aging processes.
C. Higgins Tejera, R. Noroozi, K. A. Walker et al.· medRxiv· 0 citations
Importance: Epigenetic age acceleration (EAA) has been linked to increased disease risk in adults, yet its developmental trajectories and early-life neighborhood determinants remain poorly understood. Objective: To examine associations between the neighborhood exposome at birth and EAA trajectories from early childhood through adolescence. Design, Setting, and Participants: Longitudinal cohort study using data from Project Viva, a pre-birth cohort that enrolled pregnant women in eastern Massachusetts (1999-2002). Participants included 570 children with available peripheral blood DNA methylation data, complete neighborhood characteristics, and complete covariates. Data were analyzed from 2024 to 2026. Exposures: Neighborhood exposome profiles at birth derived from 22 census tract-level characteristics across four domains (area deprivation, social fragmentation, population density, and environmental quality) using self-organizing maps. Main Outcomes and Measures: EAA was calculated at ages 3 (n=84), 8 (n=301), and 13 (n=434) years using Horvath, Skin & Blood, and Wu epigenetic clocks. Trajectories were identified using latent class linear mixed models. Associations between neighborhood profiles and EAA trajectories were estimated using multinomial mixed models. Results: Among 570 children (mean [SD] age at early childhood, 3.2 [0.4] years; 265 [46.5%] female), three EAA trajectory groups (stable, increasing, and decreasing for the Horvath and Skin & Blood clocks or low-baseline for the Wu clock) and three neighborhood profiles were identified. Compared with Profile 1 (suburban, lowest adverse exposures; n=278), children born into Profile 2 (urban, high residential instability and single-person households, and highway proximity; n=168) had greater odds of increasing EAA for Wu clock (aOR, 1.67; 95% CI, 1.03-2.69). Profile 3 (urban, high socioeconomic deprivation; n=124) showed no significant associations. Conclusions and Relevance: In this longitudinal cohort study, birth into neighborhoods characterized by high residential instability and single- person households, and highway proximity was associated with increasing Wu EAA trajectories across childhood. These findings suggest that early-life neighborhood conditions, encompassing both social and physical environmental factors, may represent targets for interventions aimed at reducing long-term disease risk. Further research is needed to clarify the implications of these findings for later health and prevention.
Q. Yuan, A. Bozack, V. Paquin et al.· medRxiv· 0 citations
