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

Award Number: R01AG071717
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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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 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $1,421,823 )
2025	2025	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	000	4	4/11/2025	NON-COMPETING CONTINUATION	$1,305,755
2025	2025	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	001	4	6/18/2025	NON-COMPETING CONTINUATION	$116,068
														Subtotal = $1,421,823

Issue Date FY: 2024 ( Subtotal = $1,203,796 )
2024	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	001	3	7/1/2024	NON-COMPETING CONTINUATION	$120,379
2024	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	000	3	1/31/2024	NON-COMPETING CONTINUATION	$1,083,417
														Subtotal = $1,203,796

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	001	2	6/29/2023	NON-COMPETING CONTINUATION	$0
2023	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	000	2	2/27/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $1,233,432 )
2022	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	002	2	9/2/2022	NON-COMPETING CONTINUATION	$1,233,432
2022	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	001	1	5/4/2022	NEW	$0
2022	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	000	1	11/1/2021	NEW	$0
														Subtotal = $1,233,432

Issue Date FY: 2021 ( Subtotal = $1,331,794 )
2021	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Aging Research	000	1	9/22/2021	NEW	$1,331,794
														Subtotal = $1,331,794

Grand Total All Awards = $5,190,845

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

Award Number: R01AG071717

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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