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

项目摘要 世界人口正在肥胖环境中老龄化，其特征是高密度脂蛋白的可用性增加。 高热量、无营养的食物和减少体力活动的需要。因此，越来越多的人 受慢性年龄相关疾病的影响，如肥胖、心脏病和糖尿病。因此， 寿命更长，但健康寿命更短，或者不受疾病影响的年数更少。这迫使 对人民、社会和国家造成重大的健康和经济负担。迫切需要发展 并测试可持续的生活方式干预措施，以减缓生物衰老的速度，延长健康寿命， 生活质量随着年龄的增长。一种这样的干预措施是热量限制（CR），其定义为吃 低于能量需求的营养充足的饮食。CR已经研究了近100年， 已经被发现可以延长许多物种的寿命和健康寿命。当在年轻人和中年人中进行测试时- 对于老年人来说，适度的CR可以改善健康状况并减缓生物衰老。尽管如此，遵守CR 随着时间的推移，这种方法的长期可行性受到质疑， 早期的CR干预并没有从更先进的干预方法中获益，即即时干预 适应性干预（JITAI）。JITAIs努力为个人提供合适的类型和数量的个性化 通过调整干预措施以适应受试者当前的需求和环境，在需要时提供支持。一 可能具有更好的依从性和可接受性的CR的可能替代方案是时间限制饮食（TRE）， 一天中有8到10个小时是吃东西的。TRE延长了啮齿动物的寿命， 根据最近的人体试验，TRE改善了疾病风险因素和衰老的生物标志物。此外，许多 即使在没有发生体重减轻的情况下，也能获得TRE的益处。为了响应RFA-AG-21-016，我们 提出一个新的规划项目，以确定CR和TRE的可行性和初步功效，该项目将 以传统的干预形式和JITAI形式提供。规划项目的数据将用于 选择CR干预措施，并确定在未来的5年试验中是否测试TRE干预措施以及测试何种TRE干预措施。 此外，与更传统的方法相比，对CR和TRE JITAI的评估至关重要， 根据这些非常不同的干预措施的负担和满意度来衡量疗效， 接近。我们的项目还将提供一套初级和次级老化的效应量估计 结果足以支持一项为期5年的试验，它将提供关于依从性的重要初步数据， 受试者满意度和安全性。最后，规划项目将汇集一个多学科小组， 来自美国各地的科学家，并允许两个研究中心建立一个共同的协议和标准化， 执行5年试验所需的程序。

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.