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

CALERIE（一种为期 2 年的热量限制干预措施）对健康寿命和衰老标志的遗留影响

• 批准号: 10365580
• 负责人: Sai Krupa Das
• 金额: $ 133.18万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10365580
• 关键词: Address; Adult; Aerobic; Age; Aging; Algorithms; Animal Model; Attenuated; Baltimore; Basal metabolic rate; Biological; Biological Aging; Biological Markers; Biological Specimen Banks; Blood; Body Composition; Body measure procedure; Brain natriuretic peptide; C-reactive protein; Caloric Restriction; Cardiometabolic Disease; Cell Aging; Chronic Disease; Clinical Trials; Cognition; Communities; Control Groups; Development; Disease; Energy Intake; Exposure to; Fatigue; Follow-Up Studies; Funding; GDF15 gene; Gait speed; General Population; Glycosylated hemoglobin A; Goals; Hand Strength; Human; Insulin; Insulin-Like Growth Factor I; Intake; Interleukin-6; Intervention; Isoprostanes; Long-Term Effects; Longitudinal Studies; Measurement; Measures; Metabolic syndrome; Metformin; Methods; N-terminal; National Institute on Aging; Nutritional; Obesity; Observational Study; Outcome; Oxidative Stress; Participant; Pattern; Phenotype; Process; Proteins; Public Health; Quality Control; Quality of life; Randomized Controlled Trials; Risk; Sampling; Sleep; TNFRSF1A gene; Testing; Urine; age related; behavior change; biobehavior; blood-based biomarker; cardiorespiratory fitness; cognitive function; cohort; comparison group; data repository; design; diet and exercise; disorder risk; effectiveness evaluation; experience; follow-up; healthspan; healthy aging; indexing; intervention participants; lifestyle intervention; middle age; motivated behavior; novel; post gamma-globulins; prevent; primary outcome; psychologic; senescence; urinary

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.

项目概要 热量限制（CR）是一种很有前途的营养策略，有可能减缓衰老过程。这 减少能量摄入的长期影响综合评估 (CALERIE) 试验，由 国家衰老研究所是第一个临床试验，证明了实现持续、 不肥胖的健康青壮年的 CR 为中等。在为期2年的CR干预期间， 参与者平均达到 12% CR，与随意摄入对照组相比，经历了 健康寿命指标显着改善，生物衰老速度减慢。总体目标 这项拟议研究的目的是检验 2 年的 CR 是否会导致生物、 人类衰老的表型和功能标志。我们假设暴露于 2 年 CR 成年早期到中期的干预可导致生物衰老率持续降低、延迟 与普通人相比，表型衰老的表现、卓越的功能衰老指数以及更高的生活质量 随意摄入。为了检验这一假设，我们将对 CALERIE 进行观察性后续研究 参与者在试验参与结束后 10 至 15 年。来自 CALERIE CR 小组的参与者将 与由 CALERIE 随意摄入对照组组成的随意摄入对照组进行比较 以及来自巴尔的摩老龄化纵向研究（BLSA）的匹配社区居住队列。井- 特征性 BLSA 队列被纳入作为比较样本，以解决高度 经过筛选的 CALERIE 对照可能比一般人群更健康，并且有很高的积极性 行为改变。 BLSA 也有严格的质量控制，并且有几个相同的结果 测量作为 CALERIE 试验，以方便比较。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 除了心理和心理健康之外，还包括成分、心肺健康、握力和认知功能。 生活质量衡量标准。还将收集血液和尿液并分析生物衰老和 心脏代谢疾病风险。将在 CALERIE CR 参与者和合并后的参与者之间进行比较 随意摄入对照组（CALERIE 随意摄入对照组和 BLSA 队列）。评估中 CALERIE 试验的遗留影响将决定早期至中期 CR 干预的有效性 成年期预防与年龄相关的慢性疾病的发生或延缓其进展。这 拟议的试验将扩大 CALERIE 数据和生物样本存储库，用于未来的研究，以推进我们的研究 对人类衰老的认识。