Introduction:
Life’s Simple 7 (LS7) comprises seven health factors and behaviors promoted by the American Heart Association to reduce cardiovascular morbidity and mortality. Despite compelling evidence of inverse association between LS7 adherence and a variety of adverse health outcomes, the epigenetic sequelae of healthy lifestyle have not been comprehensively characterized and may offer valuable insights into the underlying biological mechanisms.
Hypothesis:
We hypothesized that LS7 adherence is associated with an epigenetic signature that is consistent with the deceleration of the aging process.
Methods:
Using data from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n=853), we have estimated cross-sectional associations between epigenome-wide DNA methylation at 487,432 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells and the number of achieved LS7 goals as measured by study staff (blood pressure, body mass index, total cholesterol, and fasting glucose) or reported by the participant (diet, smoking, physical activity). The associations were tested using linear mixed models adjusted for age, sex, study site, technical artifacts (fixed effects), and family relatedness (random effect). Additionally, we tested associations between LS7 compliance and age acceleration, estimated from DNA methylation data and chronological age using two complementary validated algorithms (1: Horvath and 2: Hannum). These linear mixed models adjusted for chronological age, sex, study site, CD4+ T-cell subtype estimates (fixed effects), and family relatedness (random effect). Epigenome-wide association results were considered statistically significant if they fell under the Bonferroni corrected threshold (alpha=0.05/487,432= 1.03x10
-7
).
Results:
Methylation of an intronic CpG site in
CPT1A
, cg00574958, was positively associated with the number of achieved LS7 goals at the epigenome-wide significance level (beta= 0.008, SE= 0.001, P= 4.7x10
-8
).
CPT1A
encodes a key enzyme in the beta-oxidation process and has previously been linked to fasting triglycerides, body mass index, and adiponectin levels. Age acceleration was associated with LS7 adherence under the Hannum algorithm (beta=-0.01, SE= 0.006, P= 0.02) but not the Horvath algorithm (beta=-0.005, SE= 0.004, P= 0.18).
Conclusions:
Achievement of LS7 goals was significantly associated with methylation variation in
CPT1A
, a critical lipid metabolism gene, and was associated with age deceleration in the Hannum but not the Horvath models. Following independent replication, future studies should consider interrogating
CPT1A
methylation in relation to cardiovascular morbidity and mortality in a prospective setting.
Letter to the Editor on “Traditional Cardiovascular Risk Factors Strongly Underestimate the 5-Year Occurrence of Cardiovascular Morbidity and Mortality in Spinal Cord Injured Individuals”