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: 10451613
• 负责人: Yanbin Dong
• 金额: $ 72.09万
• 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/10451613
• 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; 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 Clinical Trials; Randomized Controlled Trials; Research; Resources; Risk Factors; Role; Sampling; Serum; Severities; Supplementation; TNF gene; Testing; Time; Woman; age related; aged; anti aging; base; 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; 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 可可产品已成为一种更广泛的食物，全球需求不断增长，而且蒸蒸日上 增加对其潜在健康益处和抗衰老生物学的兴趣。但是，可可消费的作用 在表观遗传学上，衰老基本上仍然是出乎意料的。有令人信服的证据表明 基于体外和动物模型的可可和可可衍生的黄酮的炎症作用。但是， 研究进度的关键障碍仍然缺乏明确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衰老最近成为一种强大的， 寿命和健康跨度，疾病敏感性，发病率和死亡率风险的新型预测因子。此外， 炎症是较早的发病率和死亡率的高度显着危险因素，因为许多年龄有关 包括心血管疾病（CVD）在内的疾病具有炎症发病机理。因此，干预措施 减慢或减轻表观遗传衰老和炎症对于促进健康衰老至关重要。 可可补充和多种维生素结果研究（COSMOS）是一项持续的随机，双重的 盲，安慰剂对照，高质量可可提取物补充剂的2x2阶乘RCT（含600 mg/d 黄烷醇，包括80毫克epimatechins）和多种维生素补充剂，以降低CVD和癌症的风险 在≥65岁的妇女中，年龄≥60岁。宇宙已将21,444名参与者随机分配到试验中， 包括2,006名具有生物样本的参与者，已经在基线，1年级和2年级随访中收集。 宇宙是可可提取物对男性和男性的影响的唯一大型RCT，以及多种维生素的影响 女性。这是这项拟议的辅助研究将基于父宇宙试验的基础 600的抗衰老（表观衰老和炎症）的随机可可或多种维生素补充 在基线，第1年和第2年的三个生物样本收集的代表性受试者以及测量 CVD风险因素，并在CVD结果的背景下检查这些发现。我们将测试我们的中央 假设可可补充可减少表观遗传衰老指数（例如，Ageaccelhorvath， ageaccelhannum，ageaccelgrim，ageaccelpheno和dnamtladjage）和炎症（血清HSCRP，IL- 随着时间的流逝，1β，IL-4，IL-6和TNF-α）。我们还将确定可可补充的影响在多大程度上 关于炎症和CVD危险因素是通过表观遗传衰老介导的。 诸如黑巧克力之类的可可粉产品的据称抗衰老健康益处已普及，并且 在过去十年中，增加了富含可可的产品的食用。而且，多种维生素仍然是最多的 至少有三分之一的美国成年人服用的常见饮食补充剂。它仍然是关键的公共卫生 严格测试这两种补充剂的抗衰老特性的重要性 确定其潜在效率的确定证据，并批准或驳斥其潜在的抗衰老收益。