Cardiovascular
The role of epigenetic aging in physical activity and cardiovascular mortality Judy Fan* Judy Fan Hanyang Shen David H. Rehkopf
Background:
DNA methylation (DNAm) clock, a DNAm-based measure of biological age, has been shown to reflect vascular aging that could lead to cardiovascular (CV) diseases. Although exercise-modulated CV protection has been well-studied, there is a lack of nationally representative population-based studies that examine the role of epigenetic aging in this relationship.
Objective:
This study aims to evaluate the association of physical activity and CV mortality mediated through epigenetic aging in US adults.
Methods:
US adults aged 50 years and older from NHANES 1999-2002 with available DNA specimens (n=2446) and self-reported physical activity data will be included. The intensity of physical activity will be assessed as metabolic equivalents (METs) and categorized into minimal, moderate, and vigorous according to NHANES guidelines. Heart disease specific mortality, followed through December 2019, was obtained from linked National Death Index files. To evaluate DNAm clock, DNAm assay on peripheral blood was first performed using the Illumina Infinium MethylationEPIC BeadChip. The ‘Horvath’ DNAm clock, measuring the accumulation of methyl groups to DNA, was then computed using DNAm data after quality control steps, background subtraction, and color correction, imputation, and normalizations. It was compared with chronological age to predict epigenetic aging. We will perform causal mediation modelling to assess direct and indirect effects of physical activity after considering DNAm clocks as mediator. Control variables in our analysis include age, sex, body mass index, total and HDL cholesterol, systolic and diastolic blood pressure, glycosylated hemoglobin, c-reactive protein, creatinine, race and ethnicity, occupational category, income, and education.
Results/Conclusion:
We hypothesize that epigenetic aging from DNAm clock has a moderate effect on the physical activity-CV mortality association.