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

项目摘要 热量限制（CR）是一种有前途的营养策略，有可能减缓衰老过程。的 减少能量摄入长期影响的综合评估（CALERIE）试验，由 国家老龄化研究所，是第一个临床试验，以证明实现持续， 无肥胖的健康青年和中年成人中的中度CR。在2年CR干预期间， 参与者平均达到12%的CR，与随意摄入对照组相比， 健康标志物的显著改善和生物老化速度的减缓。总体目标 这项拟议研究的目的是检查2年CR是否会导致生物学， 人类衰老的表型和功能标志。我们假设暴露于2年CR 在成年早期到中期的干预导致生物衰老的持续降低， 表型老化的表现，功能老化的上级指标，以及与 自由摄入。为了验证这一假设，我们将对CALERIE进行观察性随访研究 受试者在试验结束后10至15年。CALERIE CR组的参与者将 与由CALERIE自由采食对照组组成的自由采食对照组进行比较 以及来自巴尔的摩老龄化纵向研究（BLSA）的匹配的社区居住队列。井- 特征化的BLSA队列被包括作为比较样本，以解决高度 经过筛查的CALERIE对照组可能比一般人群更健康， 行为改变BLSA还具有严谨性、质量控制性和几个相同的结果 测量作为CALERIE试验，以便于比较。CALERIE后续研究将 包括一套全面身体和功能评估，包括静息代谢率、身体 组成，心肺功能，握力和认知功能，除了心理和 生活质量测量。还将收集血液和尿液，并分析生物老化的标志物， 心脏代谢疾病风险。将CALERIE CR参与者与合并后的 自由摄入对照组（CALERIE自由摄入对照组和BLSA队列）。评价 CALERIE试验的遗留效应将决定早期至中期CR干预的有效性。 用于预防年龄相关慢性疾病的发展或延缓其进展。的 拟议的试验将增加CALERIE数据和生物标本库，以供未来研究， 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.