Abstract P1001: Life-course Epidemiology of Cardiovascular-related Factors and Pace of Aging, Insights from Age Gene/Environment Susceptibility-Reykjavik Longitudinal Study

Background: Biological aging reflects the age and physiological function of cells and tissues. In this study, we examined the potential long-term influence of cardiovascular-related factors from midlife (mean age ~ 50) on the epigenetic aging clock measured in late life (mean age ~ 81 years). Methodology: Data on midlife demographic and cardiovascular risk factors were collected in the Reykjavik Study (RS), Iceland (n=1,553, 56.9% female). Blood-based DNA samples were collected 30 years later as a part of the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES), which is an extension of the RS. DNA methylation levels were analyzed using Illumina's Infinium MethylEPIC and were calculated as beta-values. The pace of aging was derived from the DunedinPACE epigenetic clock. Using linear regression, we examined the association between the pace of aging and the aggregated Life’s Simple 7 (LS7) score and separately its individual components, adjusting for sex, midlife chronological age, midlife educational level, white blood cell composition, and batch effects. The DunedinPACE pace of aging (PofA), LS7 score and the continuous variables within the LS7 were scaled in standard deviation (SD) units; statistical significance was set at P < 0.05. Results: Compared to never smokers, midlife current smokers, but not ex-smokers, had a higher PofA in late life (β = 0.56, 95% CI [0.45–0.67], P = 8.45e -23 ). Similarly, individuals with high BMI (β = 0.11, 95% CI [0.07–0.16], P = 2.81e -06 ) and elevated fasting glucose levels (β = 0.01, 95% CI [0.001–0.01], P = 1.42e -02 ), but not those with elevated blood pressure and total cholesterol, had a higher PofA in late life. There was a tendency for level of physical activity (none, low, medium, high) to be inversely associated with the PofA. Together, the midlife LS7 score was significantly associated (β = -0.10, 95% CI [-0.13 – -0.07], P = 1.77e -12 ) with the PofA. Conclusion: Our life-course epidemiological analyses highlight the long-term influence of cardiovascular-related factors on the pace of aging in late life. Early interventions focused on smoking cessation, promoting regular exercise, and managing BMI and glucose levels may help delay biological aging and reduce the future burden of age-related diseases.