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

项目总结 世界人口正在肥胖环境中老龄化，其特征是高可获得性增加 高热量、非营养的食物和减少体力活动的需要。因此，比以往任何时候都更多的人 受与年龄相关的慢性疾病的影响，如肥胖、心脏病和糖尿病。因此，人们是 寿命更长，但健康寿命较短，或不受疾病影响的年数较少。这就强加于 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，并提高 随着人们年龄的增长，生活质量。一种这样的干预是卡路里限制(CR)，它的定义是吃一种 低于能量要求的营养充足的饮食。对CR的研究已有近100年的历史， 已被发现可以延长许多物种的寿命和健康范围。当在青年和中年进行测试时- 老年人，适度的CR延长了健康寿命，延缓了生物衰老。尽管如此，坚持使用CR 已被发现随着时间的推移而减少，但这一方法的长期可行性受到了质疑 早期的CR干预没有受益于更先进的干预方法，即及时干预 适应性干预(JITAI)。JITAI努力为个人提供合适的个性化类型和数量 在需要时提供支持，使干预措施适应受试者目前的需要和环境。一个 可能具有更好的依从性和可接受性的CR的替代方案是限时进食(Tre)， 这包括在一天中的8到10个小时内吃东西。Tre延长了啮齿动物的寿命， 而且，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记物。此外，还有许多 即使在没有发生体重减轻的情况下，也能获得TrE的好处。为回应RFA-AG-21-016，我们 提出一个新的规划项目，以确定CR和TRE的可行性和初步效果，该项目将 将以传统干预形式和联合技术援助的形式交付。来自规划项目的数据将用于 选择CR干预，并确定在未来5年的试验中是否测试TRE干预以及测试哪种类型的TRE干预。 此外，与更传统的方法相比，对CR和TRE JITAI的评估是至关重要的，以便我们能够 将疗效与这些截然不同的干预措施的负担和满意度进行权衡 接近了。我们的项目还将提供一套初级和次级老化的效果大小估计 结果足以支持一项为期5年的试验，它将提供关于依从性和 主体满意度和安全性。最后，规划项目将汇集一个多学科的团队 来自美国各地的科学家，并允许这两个研究地点建立共同的协议并标准化 执行为期5年的审判所需的程序。

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.