Abstract
BACKGROUND: The metabolic syndrome (MetS) is a collection of metabolic disturbances that can lead to various cardiovascular diseases. Previous studies have shown a more adverse metabolic risk profile is associated with more advanced biological aging. The associations between epigenetic biomarkers of age with MetS, however, are not well understood. We therefore investigated the associations between epigenetic age acceleration and MetS severity score and incident MetS. RESULTS: A subset of study participants with available whole blood at examination years 15 and 20 from the Coronary Artery Risk Development in Young Adults Study underwent epigenomic profiling using the Illumina MethylationEPIC Beadchip (~ 850,000 sites). Intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA) were calculated from DNA methylation levels. The MetS severity score was positively associated with IEAA at years 15 (P = 0.016) and 20 (P = 0.016) and EEAA at year 20 (P = 0.040) in cross-sectional analysis. IEAA at year 20 was significantly associated with incident MetS at year 30 (OR = 1.05 [95% CI 1.01, 1.10], P = 0.028). CONCLUSIONS: To our knowledge, this is the first report of the longitudinal association between epigenetic age acceleration and MetS. These findings suggest that a higher MetS severity score is associated with accelerated epigenetic aging and such aging may play a role in the development of metabolic disorders, potentially serving as a useful biomarker of and early detection tool for future MetS.