A planning project to pilot test and optimize dietary approaches to slow aging and design a long-term trial

试点测试和优化饮食方法以延缓衰老并设计长期试验的规划项目

• 批准号: 10281902
• 负责人: CORBY K MARTIN
• 金额: $ 107.22万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-05 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10281902
• 关键词: Adherence; Affect; Age; Aging; Animals; Applications Grants; Attenuated; Autophagocytosis; Biological; Biological Aging; Biological Markers; Body Weight decreased; Body mass index; Caloric Restriction; Cell Aging; Chronic; Clinical Trials; Consultations; DNA Methylation; Data; Desire for food; Diabetes Mellitus; Diet; Dietary Intervention; Disease; Doctor of Philosophy; Early Intervention; Eating; Economic Burden; Environment; Epigenetic Process; Evaluation; Feedback; Focus Groups; Food; Future; Genomic Instability; Health Technology; Heart Diseases; Hour; Human; Impairment; Individual; Infrastructure; Intervention; Intervention Studies; Learning; Longevity; Manuals; Measures; Methods; Nutritional; Obesity; Outcome; Oxidative Stress; Participant; Patient Outcomes Assessments; Physical activity; Pilot Projects; Population; Procedures; Protocols documentation; Quality of life; Randomized; Research Personnel; Risk Factors; Rodent; Safety; Scientist; Site; Societies; Standardization; Testing; Time; Time-restricted feeding; Writing; adaptive intervention; arm; base; cardiovascular risk factor; comparative effectiveness trial; design; detection of nutrient; diabetes risk; dietary approach; disorder risk; doubly-labeled water; exhaustion; feasibility trial; health economics; healthspan; healthy aging; improved; indexing; intercellular communication; intervention effect; lifestyle intervention; mHealth; middle age; mitochondrial dysfunction; multidisciplinary; novel; novel strategies; obesogenic; pilot trial; proteostasis; response; satisfaction; stem cells; telomere; therapy design; trial design

PROJECT SUMMARY The world's population is aging in an obesogenic environment characterized by increased availability of high caloric, non-nutritious foods and reduced needs for physical activity. As a result, more people than ever are affected by chronic age-associated diseases, such as obesity, heart disease and diabetes. Thus, people are living longer but with shorter healthspans, or fewer years that are unaffected by disease. This imposes significant health and economic burdens on people, societies and nations. There is a critical need to develop and test sustainable lifestyle interventions to slow the rate of biological aging, extend healthspan and enhance quality of life as people age. One such intervention is calorie restriction (CR), which is defined as eating a nutritionally adequate diet that is below energy requirements. CR has been studied for almost 100 years and has been found to extend the lifespan and healthspan of numerous species. When tested in young and middle- aged humans, modest CR improves healthspan and slows biological aging. Nonetheless, adherence to CR has been found to decrease over time, calling into question the long-term viability of this approach, though earlier CR interventions did not benefit from a more advanced intervention approach, namely, a Just-in-Time Adaptive Intervention (JITAI). JITAIs strive to provide individuals with the right type and amount of personalized support when needed by adapting intervention delivery to the present needs and environment of the subject. A possible alternative to CR that may have better adherence and acceptability is time-restricted eating (TRE), which involves eating one's food in an 8 to 10-hour period of the day. TRE extends the lifespan of rodents, and, based on recent human trials, TRE improved disease risk factors and biomarkers of aging. Further, many benefits of TRE were achieved even when weight loss did not occur. In response to RFA-AG-21-016, we propose a novel planning project to determine the feasibility and preliminary efficacy of CR and TRE, which will be delivered in traditional intervention formats and as JITAIs. Data from the planning project will be used to select the CR intervention and identify if and what type of TRE intervention will be tested in a future 5-year trial. Further, evaluation of CR and TRE JITAIs, in comparison to more traditional approaches, is critical to allow us to weigh efficacy in relation to the burden of, and satisfaction with, these very different intervention approaches. Our project will also provide effect size estimates for a suite of primary and secondary aging outcomes to adequately power a 5-year trial, and it will provide important preliminary data on adherence and subject satisfaction and safety. Finally, the planning project will bring together a multidisciplinary team of scientists from across the US and allow the two study sites to establish a common protocol and standardize procedures necessary to execute a 5-year trial.

项目摘要 世界的人口正在肥胖环境中衰老，其特征是增加 热量，非滋补食品以及减少体育锻炼的需求。结果，比以往任何时候都多 受慢性年龄相关疾病的影响，例如肥胖，心脏病和糖尿病。因此，人们是 寿命更长，但寿命较短，或者较少的年限不受疾病影响。这强加了 对人，社会和国家的重大健康和经济负担。有迫切需要发展 并测试可持续的生活方式干预措施以减慢生物衰老的速度，扩展健康状态并增强 随着人们的年龄，生活质量。一种这样的干预是卡路里限制（CR），该干预被定义为 营养足够的饮食低于能源需求。 CR已研究了将近100年， 已发现可以延长许多物种的寿命和健康状态。在年轻和中间测试时 老年人，适度的CR可改善健康状态并减慢生物衰老。尽管如此，坚持CR 已经发现随着时间的流逝会减少，但质疑这种方法的长期可行性 较早的CR干预措施并未受益于更高级的干预方法，即 自适应干预（Jitai）。 Jitais努力为个人提供正确的个性化类型和数量 在需要的情况下，通过调整干预措施来提供对主题的当前需求和环境的支持。一个 可能具有更好依从性和可接受性的CR的替代方法是时间限制的饮食（TRE）， 这涉及在一天的8至10小时内吃食物。 tre延长了啮齿动物的寿命， 并且，根据最近的人类试验，TRE改善了疾病的危险因素和衰老的生物标志物。此外，许多 即使没有发生体重减轻，也可以实现TRE的好处。为了响应RFA-AG-21-016，我们 提出一个新颖的计划项目，以确定CR和TRE的可行性和初步效力，这将 以传统的干预格式和Jitais交付。计划项目的数据将用于 选择CR干预措施，并在未来的5年试验中确定是否和哪种类型的TRE干预措施将进行测试。 此外，与更传统的方法相比，对CR和Tre Jitais的评估对于允许我们至关重要 与这些截然不同的干预措施的负担和满意相关的功效 方法。我们的项目还将为一组主要和中学的效果尺寸估计 有效的结果为5年的试验供电，它将提供有关依从性和的重要初步数据 主题满意度和安全性。最后，计划项目将汇集一个多学科团队 来自美国各地的科学家，允许两个研究站点建立一个共同的协议并标准化 执行5年审判所需的程序。