Dietary Fatty Acids and Epigenetic Aging in US Adults: Results from the National Health and Nutrition Examination Survey.

Fatty acids are involved in disease risk and aging processes. In the US National Health and Nutrition Examination Survey (1999-2002), we tested for associations of total, saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA), and subtypes of dietary fatty acids with DNA methylation-based aging biomarkers, adjusting for age, BMI, total energy intake, and sociodemographic and behavioral factors (N=2,260). Higher SFA and MUFA were associated with greater GrimAge2, an aging biomarker of mortality; PUFA was associated with lower Horvath1, Hannum, and PhenoAge ( <0.05). Omega-3 and the PUFA:SFA ratio were negatively associated with Horvath1, Hannum, Vidal-Bralo, and PhenoAge. Notably, a one-unit increase in PUFA:SFA was associated with 1.05 years lower PhenoAge (95% CI=-1.87, -0.22). There were consistent trends of positive associations of SFA subtypes and negative associations of PUFA subtypes with epigenetic aging; associations of MUFA subtypes varied. Future studies, including randomized controlled trials, are needed to investigate causality and downstream clinical outcomes.