Abstract 008: Effect of a daily multivitamin on 2 year changes in DNA methylation measures of biological aging: Findings from the COSMOS Randomized Clinical Trial

Introduction: Although some trials have reported that multivitamin-multimineral (MVM) supplements reduce age-related chronic conditions such as cancer, cataracts, and cognitive decline among older adults, whether MVM slows the aging process remains unknown. Hypothesis: We hypothesized that a daily MVM could reduce biological aging measured by DNA methylation after 2 years of follow-up in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS). Methods: COSMOS is a large, randomized, double-blind, placebo-controlled, 2×2 factorial trial testing a daily MVM (Centrum Silver) and cocoa extract among women aged ≥65 y and men aged ≥60 y free of major cardiovascular disease and recently diagnosed cancer. We included 958 participants from the COSMOS Blood subcohort with biospecimens collected at baseline, year 1, and year 2. We calculated five epigenetic aging measures encompassing the first generation trained on chronological age (PCHorvath, PCHannum), the second generation trained on all-cause mortality (PCPhenoAge, PCGrimAge), and the third generation trained on pace of aging (DunedinPACE) on the Infinium Human Methylation EPIC+ Array. For the first two generations, we calculated age acceleration (Accel) by residualizing these clocks for chronological age. Linear mixed-effects models evaluated the treatment effects of a MVM on each measure. Results: The mean age was 70.2±5.6 years, and 482 (50.3%) were female. Compared with placebo, daily MVM use significantly reduced the second generation of age clocks, with a between-group difference in yearly change of -0.111 years (95% CI, -0.203 to -0.018; P=0.02) for PCGrimAge Accel and -0.209 years (-0.405 to -0.013; P=0.037) for PCPhenoAge Accel. The effect of daily MVM use was not significant for PCHorvath Accel, PCHorvath Accel, or DunedinPACE. When stratified by baseline epigenetic aging measures, the effect of MVM on PCGrimAge Accel was more pronounced among those with higher baseline PCGrimAge Accel (-0.201 [-0.334 to -0.068]) than their counterparts (-0.014 [-0.135 to 0.107]; P interaction=0.041). The effect was consistent when stratified by other baseline characteristics.. Conclusion: Our study provides the first evidence from a large-scale, long-term, randomized controlled trial that MVM supplementation potentially slows biological aging among older adults, as measured by the PhenoAge and GrimAge epigenetic clocks, with more pronounced effects among those with greater baseline accelerated biological aging.