R01AG071717

Legacy Effects of CALERIE, a 2-Year Calorie Restriction Intervention, on Hallmarks of Healthspan and Aging - 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 an average of 12% CR 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 will also 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.

Trustees Of Tufts College

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Boston, Massachusetts 021111524 United States

Single Zip Code

Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional) (PA-20-272)

Amendment Since initial award the End Date has been extended from 05/31/26 to 01/31/27 and the total obligations have increased 299% from $1,331,794 to $5,317,155.