Effect of randomized cocoa supplementation on inflammaging and epigenetic aging

随机补充可可对炎症和表观遗传衰老的影响

• 批准号: 10630875
• 负责人: Yanbin Dong
• 金额: $ 72.15万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10630875
• 关键词: Acceleration; Adult; Aging; Ancillary Study; Animal Model; Anti-Inflammatory Agents; Biological Aging; Biology of Aging; Blood; C-reactive protein; Cardiovascular Diseases; Chocolate; Chronic; Cocoa Powder; Collection; Consumption; DNA Methylation; Darkness; Dietary Intervention; Disease; Disease Outcome; Disease susceptibility; Double-Blind Method; Effectiveness; Elderly; Epigenetic Process; Flavanol; Food; Gene Expression; Health; Health Benefit; Human; In Vitro; Inflammaging; Inflammation; Inflammatory; Interleukin-1 beta; Interleukin-4; Interleukin-6; Intervention; Longevity; Malignant Neoplasms; Measures; Mediating; Molecular; Morbidity - disease rate; Multivitamin; Observational Study; Outcome; Outcome Study; Parents; Participant; Pathogenesis; Personal Satisfaction; Placebo Control; Placebos; Property; Public Health; Randomized; Randomized, Controlled Trials; Research; Resources; Risk Factors; Risk Reduction; Role; Serum; Severities; Supplementation; TNF gene; Testing; Time; Woman; age related; aged; anti aging; cardiovascular disorder risk; cohort; cost; cost effective; cytokine; dietary supplements; epicatechin; follow-up; food consumption; functional decline; healthspan; healthy aging; human old age (65+); indexing; insight; interest; lifestyle intervention; men; mortality; mortality risk; novel; public health relevance; randomized, clinical trials; recruit

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.

项目摘要/摘要 可可产品已经成为一种广泛消费的食品，世界各地的需求都在稳步增长 人们对其潜在的健康益处和抗衰老生物学越来越感兴趣。然而，可可消费的作用 关于表观遗传衰老的研究基本上还没有被探索。已经有令人信服的证据证明反- 基于体外和动物模型的可可和可可衍生黄烷醇的炎症作用。然而，a 研究进展的关键障碍仍然是缺乏确定的大规模随机对照试验(RCT)。 包括DNA甲基化变化的加速表观遗传老化最近已经成为一种强大的 寿命和健康期限、疾病易感性、发病率和死亡风险的新预测指标。此外， 炎症是老年人发病率和死亡率的一个非常重要的危险因素，因为许多与年龄有关的因素 包括心血管疾病(CVD)在内的疾病都有炎症的发病机制。因此，干预措施 延缓或减轻表观遗传衰老和炎症是促进健康衰老的关键。 可可补充剂和多种维生素结果研究(COSMOS)是一项正在进行的随机双盲研究。 高品质可可提取物补充剂(含600 mg/d)的2x2因子盲法安慰剂对照随机对照试验 黄烷醇，包括80毫克表儿茶素)和多种维生素补充剂，以降低心血管疾病和癌症的风险 女性≥年龄65岁，男性≥年龄60岁。宇宙航空公司随机选择了21,444名参与者参加试验， 包括2,006名参与者，他们在基线、第一年和第二年的后续行动中已经收集了生物样本。 Cosmos是唯一一家大型随机对照试验，测试可可提取物对女性和男性的影响，以及对多种维生素的影响 女人。因此，这项拟议的辅助研究将建立在父母COSMOS试验的基础上，以检查 600例随机补充可可或复合维生素的抗衰老(表观衰老和炎症) 具有代表性的受试者，在基线、第一年和第二年收集了三个生物样本，并进行了测量 心血管疾病的危险因素，并结合心血管疾病的结果来检验这些发现。我们将测试我们的中央 补充可可降低表观遗传衰老指数的假设(例如，AgeAccelHorvath， AgeAccelHannum、AgeAccelGrim、AgeAccelPheno和DNAmTLadjAge)和炎症(血清hsCRP、IL- 1β、IL-4、IL-6和肿瘤坏死因子-α)随时间变化。我们还将确定可可补充剂的影响程度。 炎症和心血管疾病的危险因素是由表观遗传衰老介导的。 据称，黑巧克力等富含可可的产品对抗衰老健康有好处，它普及了 过去十年，可可产品的消费量有所增加。此外，复合维生素仍然是最多的 至少三分之一的美国老年人服用常见的膳食补充剂。它仍然是至关重要的公共卫生问题 通过大型RCT严格测试这两种补充剂的抗衰老性能非常重要 证明其潜在功效的确凿证据，并批准或驳斥其潜在的抗衰老益处。