Abstract

Introduction: DNA methylation age acceleration (DNAmAA) scores, which are epigenetic biomarkers of aging and physiological responses to environmental factors such as lifestyle and health behaviors, have been previously shown to be associated with cardiovascular disease (CVD) outcomes and all-cause mortality. Life’s Simple 7 (LS7) is a tool promoted by the American Heart Association that summarizes individual adherence to seven key cardiovascular health and lifestyle metrics. We hypothesized that greater LS7 adherence would be associated with lower DNAmAA, consistent with slower biological aging. Methods: Associations between DNAmAA and LS7 were estimated separately in 2,312 African American (AA) and 1,036 European American (EA) adult participants in the Atherosclerosis Risk in Communities (ARIC) study. Visit 1 (mean age = 53 yrs in AA adults, 56 yrs in EA adults) LS7 was calculated for each participant, with 0, 1, or 2 points assigned by adherence to each component: smoking status, body mass index, physical activity, diet, plasma cholesterol, blood pressure, and fasting glucose . The summed score was categorized as inadequate (0-4), intermediate (5-9), or ideal (10-14) LS7 status. Three different previously published DNAmAA scores (Horvath, Hannum, and PhenoAge), were calculated using data from the Illumina HM450K BeadChip on stored frozen leukocytes available at visit 2 or 3 (approximately 3-6 years later). Linear regression models tested the association of LS7 category with DNAm scores, adjusting for sex, chronological age, education, income, study center, alcohol use , white blood cell count , imputed WBC type proportions using the Houseman method, Illumina HumanExome Beadchip principal components for genetic ancestry , and Illumina HM450K control probe principal components for technical adjustment. The Bonferonni-corrected threshold for statistical significance across the six tests was set to p<0.0083 (0.05/6). Results: Among AA adults, ideal LS7 status (compared to poor status) was associated with a 1 year lower PhenoAge acceleration (β=-1.03; 95%CI=-1.70, -0.35; p=0.003), but was not significantly associated with Horvath or Hannum DNAmAA scores. In EA adults, ideal LS7 adherence was not significantly associated with any of the three DNAmAA scores, but the direction and magnitude of the PhenoAge acceleration association in EA was similar to that in AA (β=-0.96; 95%CI=-2.66, 0.73; p=0.27). Conclusions: African American adults with ideal LS7 status had lower PhenoAge acceleration than African Americans who did not, suggesting that heart-healthy lifestyles may slow biological aging processes in this population. Future studies should examine the prospective associations of changes in healthy lifestyle and changes in epigenetic biomarkers of aging as well as modifiers of this relationship.

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