Sunday, May 11, 2025
5/11/2025
Effect of randomized cocoa supplementation on inflammaging and epigenetic aging - PROJECT SUMMARY/ABSTRACT Cocoa products have become a widely consumed food, with growing demand across the world and steadily increasing interest in its potential health benefits and anti-aging biology. However, the role of cocoa consumption on epigenetic aging remains essentially unexplored. There has been compelling evidence for the anti- inflammatory role of cocoa and cocoa-derived flavanols based upon in vitro and animal models. However, a critical barrier of research progress remains the lack of definitive large-scale randomized controlled trials (RCTs). Accelerated epigenetic aging that comprises DNA methylation changes has recently emerged as a powerful, novel predictor for lifespan and health span, disease susceptibility, morbidity, and mortality risk. Further, inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly, as many age-related diseases including cardiovascular disease (CVD) share an inflammatory pathogenesis. As such, interventions to slow or mitigate epigenetic aging and inflammaging are critical for promoting healthy aging. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is an ongoing randomized, double- blind, placebo-controlled, 2x2 factorial RCT of a high-quality cocoa extract supplement (containing 600 mg/d flavanols, including 80 mg epicatechins), and a multivitamin supplement to reduce the risk of CVD and cancer in women aged ≥65 years and men aged ≥60 years. COSMOS has randomized 21,444 participants into the trial, including 2,006 participants with bio-samples already collected at baseline, year 1 and year 2 follow-up. COSMOS is the only large RCT testing the effects of cocoa extract in women and men, and for multivitamins in women. Thus, this proposed ancillary study will build upon the parent COSMOS trial to examine the effects of randomized cocoa or multivitamin supplementation on anti-aging (epigenetic aging and inflammaging) in 600 representative subjects with three bio-sample collections at baseline, year 1, and year 2, as well as measured CVD risk factors, and examining these findings in the context of CVD outcomes. We will test our central hypotheses that cocoa supplementation reduces epigenetic aging indices (e.g., AgeAccelHorvath, AgeAccelHannum, AgeAccelGrim, AgeAccelPheno, and DNAmTLadjAge) and inflammaging (serum hsCRP, IL- 1β, IL-4, IL-6, and TNF-α) over time. We will also determine to what extent the effects of cocoa supplementation on inflammaging and CVD risk factors are mediated by epigenetic aging. The purported anti-aging health benefits of cocoa-rich products such as dark chocolate have popularized and increased consumption of cocoa-rich products over the past decade. Moreover, multivitamins remain the most common dietary supplement taken by at least one-third of older US adults. It remains of critical public health importance to rigorously test the anti-aging properties of these two supplements via large RCTs for more definitive evidence of their potential efficacy, and to approve or refute their potential anti-aging benefits.
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