Abstract 21: Lipid Metabolites Are Associated With Epigenetic Aging Acceleration in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Abstract

Background: Epigenetic aging measures including phenotypic aging (PA) and extrinsic epigenetic age acceleration (EEAA) have been associated with age-related diseases and conditions that include cardiovascular diseases, diabetes, and cancer. However, associations between epigenetic aging and lipids have not been widely investigated. Hypothesis: We hypothesized that adverse lipid metabolite profiles are associated with epigenetic age acceleration. Methods: We estimated measures of epigenetic age acceleration in 957 white and black participants from the CARDIA Study with whole-genome blood DNA methylation profiling by the Illumina EPIC array at Year 20 (Y20; ages 38-52). We used separate linear regression models to examine cross-sectional associations of PA and EEAA estimates with fasting triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels after adjusting for race, sex, education, alcohol intake, smoking status and physical activity. Results: Participants were 51% female (n=490) and 39% black (n=393) with mean chronological age 45±4 years. Compared with participants in the 1st tertile of TG, those in the 2nd tertile had 1.32 years older PA (95%CI 0.33-2.30) and 1.04 years older EEAA (95%CI 0.22-1.87); those in the 3rd tertile had 1.78 years older PA (95%CI 0.75-2.81) and 1.09 years older EEAA (95%CI 0.23-1.95). Compared to participants in the 1st tertile of HDL-C, those in the 3rd tertile had decreased EEAA by 1.21 years (95%CI -2.16--0.27). There were no significant differences of PA or EEAA among participants of LDL-C tertiles. (Figure 1.) Conclusions: Adverse lipid metabolites (TG and HDL-C) are associated cross-sectionally with accelerated epigenetic aging. Further studies are needed to understand the longitudinal associations between epigenetic aging and adverse lipid profiles as well as the potential mechanisms that underlie these associations.