Legacy Effects of CALERIE, a 2-year Calorie Restriction Intervention, on Hallmarks of Healthspan and Aging

项目总结 卡路里限制(CR)是一种很有前途的营养策略，有可能减缓衰老过程。这个 减少能量摄入的长期影响的综合评估(CALERIE)试验，由 是第一个证明实现持续的、 健康、中青年、非肥胖者CR值适中。在为期两年的CR干预期间， 参与者平均获得12%的CR，与随意摄入控制组相比，他们经历了 健康寿命的标志显著改善，生物衰老速度放缓。首要目标是 这项拟议的研究的目的是检查2年的CR是否会导致生物学上的长期改善， 人类衰老的表型和功能特征。我们假设接触两年的CR 成年早期到中期的干预导致生物衰老的比率持续较低，延迟 表型老化的表现，功能老化的优越指标，以及更高的生活质量 即席摄入量。为了验证这一假设，我们将对CALERIE进行一项观察性跟踪研究 受试者在试验结束后10至15年。CALERIE CR组的参与者将 与自由摄入量对照组比较，自由摄入量对照组由自由摄入量对照组组成 和来自巴尔的摩老龄化纵向研究(BLSA)的匹配的社区居住队列。这口井- 特性化的BLSA队列作为比较样本包括在内，以解决人们对高度 筛查的CALERIE控制组可能比普通人群更健康，对 行为改变。BLSA也具有严谨、质量控制和几个相同的结果 测量结果与CALERIE试验相同，以便于比较。拟议的CALERIE后续研究将 包括一套全面的身体和功能评估，包括静息代谢率、身体 成分，心肺健康，握力和认知功能，除了心理和 生活质量衡量标准。血液和尿液也将被收集和分析，以确定生物老化和 心脏代谢性疾病风险。将对CALERIE CR参与者和合并后的 自由摄入量对照组(CALERIE自由摄入量对照组和BLSA队列)。正在评估 CALERIE试验的遗留效应将决定CR干预在早期到中期的有效性 预防或延缓与年龄相关的慢性疾病进展的成年期。这个 拟议的试验将增强CALERIE数据和生物质谱库，用于未来的研究，以促进我们的 对人类衰老的理解。

PROJECT SUMMARY Calorie restriction (CR) is a promising nutritional strategy with the potential to slow the aging process. The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, funded by the National Institute on Aging, was the first clinical trial to demonstrate the feasibility of achieving sustained, moderate CR in healthy, young and middle-aged adults without obesity. During the 2-year CR intervention, participants achieved 12% CR on average and, compared to an ad libitum intake control group, experienced remarkable improvements in markers of healthspan and a slower rate of biological aging. The overarching goal of this proposed study is to examine whether 2 years of CR results in long-term improvements in the biological, phenotypic, and functional hallmarks of human aging. We hypothesize that exposure to a 2-year CR intervention in early to mid-adulthood results in sustained lower rates of biological aging, delayed manifestations of phenotypic aging, superior indices of functional aging, and greater quality of life compared to ad libitum intake. To test this hypothesis, we will conduct an observational follow-up study of CALERIE participants 10 to 15 years after the end of their trial participation. Participants from the CALERIE CR group will be compared with an ad libitum intake comparison group composed of the CALERIE ad libitum control group and a matched community-dwelling cohort from the Baltimore Longitudinal Study of Aging (BLSA). The well- characterized BLSA cohort is included as a comparison sample to address the concern that the highly screened CALERIE controls may have been healthier than the general population and highly motivated for behavior change. The BLSA also has the rigor, quality control, and several of the same outcome measurements as the CALERIE trial to facilitate comparisons. The proposed CALERIE follow-up study will include a comprehensive set of physical and functional assessments, including resting metabolic rate, body composition, cardiorespiratory fitness, grip strength, and cognitive function, in addition to psychological and quality-of-life measures. Blood and urine also will be collected and analyzed for markers of biological aging and cardiometabolic disease risk. Comparisons will be made between CALERIE CR participants and the combined ad libitum intake comparison group (the CALERIE ad libitum control group and the BLSA cohort). Evaluating legacy effects of the CALERIE trial will determine the effectiveness of a CR intervention in early to mid- adulthood for preventing the development or delaying the progression of age-related chronic disease. The proposed trial will augment the CALERIE data and biospecimen repository for future research to advance our understanding of human aging.