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.

项目摘要 卡路里限制（CR）是一种有希望的营养策略，有可能减慢衰老过程。这 全面评估减少能源摄入量（Calerie）试验的长期影响，由 美国国家衰老研究所是第一个证明实现持续的可行性的临床试验 在没有肥胖症的健康，年轻和中年成年人中，CR中等。在两年的CR干预期间， 参与者平均获得了12％的CR，并且与自发摄入对照组相比 HealthSpan的标志物和生物衰老速度较慢的标志都显着改善。总体目标 这项拟议的研究是检查2年的CR是否会导致生物学的长期改善， 表型和人类衰老的功能标志。我们假设暴露于2年CR 干预早期至中期导致持续的生物老化率较低，延迟 与表型衰老的表现，功能衰老的出色指标以及更高的生活质量相比 随意摄入。为了检验这一假设，我们将对热量的观察性随访研究 参与者参加试验结束后10到15年。 Calerie CR组的参与者将 将其与自由摄入比较组组成 以及来自巴尔的摩衰老纵向研究（BLSA）的匹配的社区居民队列。福 包括BLSA队列的特征作为比较样本，以解决高度的关注 筛选的热量控制可能比普通人群更健康，并且有高度动力 行为改变。 BLSA还具有严格的质量控制和几个相同的结果 测量作为钙化试验，以促进比较。拟议的热门随访研究将 包括一组全面的身体和功能评估，包括静息代谢率，身体 除了心理和心理和 生活质量措施。还将收集和分析血液和尿液的生物衰老和 心脏代谢疾病风险。将在Calerie CR参与者和合并的合并中进行比较 自发摄入比较组（库列氏症对照组和BLSA队列）。评估 Calerie试验的遗产影响将决定CR干预在早期至中期的有效性 为防止发展或延迟与年龄相关的慢性疾病的发展的成年。这 拟议的试验将增强卡尔丽数据和生物循环库以未来的研究，以促进我们的 对人类衰老的理解。