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

基本信息

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
项目类别：
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

项目摘要

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，并且稳步增长然而，人们对其潜在的健康益处和抗衰老生物学的作用越来越感兴趣。关于表观遗传衰老的研究基本上尚未被探索，目前已经有令人信服的证据表明抗衰老的作用。然而，基于体外和动物模型的可可和可可源黄烷醇的炎症作用。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。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）在内的多种疾病都具有炎症发病机制，因此需要采取干预措施。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 COSMOS 将 21,444 名参与者随机纳入该试验，其中年龄 ≥ 65 岁的女性和年龄 ≥ 60 岁的男性。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。因此，这项拟议的辅助研究将以母体 COSMOS 试验为基础，以检验女性的影响。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 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心。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- 随着时间的推移，我们还将确定可可补充剂的影响程度。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，此外，在过去十年中，富含可可产品的消费量有所增加，而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的常见膳食补充剂，它仍然对公共健康至关重要。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。