Abstract
BACKGROUND: Epigenetic modifications linked to biological aging, like DNA methylation (DNAm), may serve as biomarkers for future cardiometabolic disease risk. However, existing studies have focused on older adults, overlooking the early-life origins of cardiometabolic health. METHODS: Among 378 participants from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study, we measured DNAm repeatedly from birth to age 18 years to calculate 4 epigenetic aging (EA) biomarkers: Horvath, Skin & Blood, Intrinsic epigenetic age, and DNAm Telomere Length (DNAmTL). We then developed a novel measure of cumulative EA spanning from birth to age 18 years. Using multinomial logistic and multivariable linear regression models, we examined associations between cumulative EA and several indicators of cardiometabolic health at 18 years. RESULTS: We observed an increased risk of obesity with an interquartile range increase in cumulative EA by Horvath (relative risk [RR], 2.61 [95% CI, 1.79-3.80]), Skin & Blood (RR, 2.76 [95% CI, 1.89-4.03]), and Intrinsic epigenetic age (RR, 1.61 [95% CI, 1.11-2.34]), whereas DNAm TL decreased obesity risk (RR, 0.32 [95% CI, 0.22 -0.45]). Similarly, cumulative EA was associated with higher body mass index, waist circumference, body fat percentage, systolic blood pressure, mean arterial pressure, and resting pulse/heart rate at age 18 years. CONCLUSIONS: Cumulative EA throughout childhood predicts young adult cardiometabolic health and may signal increased risk for later cardiometabolic disease, highlighting the value of life-course epigenetic clocks as biomarkers for early-life health interventions.