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.

项目概要/摘要 可可产品已成为一种广泛消费的食品，世界各地的需求不断增长，并且稳步增长 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 表观遗传衰老的机制基本上尚未被探索。已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源黄烷醇的炎​​症作用。然而，一个 研究进展的关键障碍仍然是缺乏明确的大规模随机对照试验（RCT）。 包括 DNA 甲基化变化在内的加速表观遗传衰老最近已成为一种强大的、 寿命和健康寿命、疾病易感性、发病率和死亡风险的新预测因子。更远， 炎症是老年人发病和死亡的一个非常重要的危险因素，因为许多与年龄相关的炎症 包括心血管疾病（CVD）在内的疾病都具有炎症发病机制。因此，干预措施 减缓或减轻表观遗传衰老和炎症对于促进健康衰老至关重要。 可可补充剂和多种维生素结果研究 (COSMOS) 是一项正在进行的随机、双重研究 高品质可可提取物补充剂（含 600 毫克/天）的盲法、安慰剂对照、2x2 析因随机对照试验 黄烷醇，包括 80 毫克表儿茶素）和多种维生素补充剂，可降低 CVD 和癌症的风险 女性年龄≥65岁，男性年龄≥60岁。 COSMOS 随机分配了 21,444 名参与者参加试验， 包括 2,006 名参与者，他们已在基线、第一年和第二年随访时收集了生物样本。 COSMOS 是唯一一项大型随机对照试验，测试可可提取物对女性和男性的影响，以及多种维生素对女性和男性的影响。 女性。因此，这项拟议的辅助研究将建立在母体 COSMOS 试验的基础上，以检验以下因素的影响： 随机补充可可或多种维生素以抗衰老（表观遗传衰老和炎症）600 例 具有代表性的受试者在基线、第一年和第二年采集了三个生物样本，并进行了测量 CVD 危险因素，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 补充可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 TNF-α）随时间的变化。我们还将确定补充可可的效果到什么程度 炎症和心血管疾病危险因素是由表观遗传衰老介导的。 黑巧克力等富含可可产品的抗衰老健康功效已广为人知， 过去十年中富含可可产品的消费量增加。此外，复合维生素仍然是最 至少三分之一的美国老年人服用的常见膳食补充剂。它仍然对公共卫生至关重要 通过大型随机对照试验严格测试这两种补充剂的抗衰老特性非常重要 其潜在功效的明确证据，并批准或反驳其潜在的抗衰老功效。