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Impact of Time-Restricted Feeding in Reducing Cancer Risk Through Optimizing Mitochondria Function

Award Number: R01CA258221
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Impact of Time-Restricted Feeding in Reducing Cancer Risk Through Optimizing Mitochondria Function - Project Summary This application, in response to RFA-CA-004 “Research Answers to National Cancer Institute's (NCI) Provocative Questions (R01 Clinical Trial Optional),” will address “PQ2: How does intermittent fasting affect cancer incidence, treatment response, or outcome?” Obesity and age are two major risk factors for cancer development. Thus, therapeutic interventions that prevent or delay the development of excessive weight gain and/or age-associated physiological dysfunction hold great promise for reducing cancer risk in the increasingly obese and elderly global population. One such intervention is time-restricted eating (TRE), a pragmatic form of intermittent fasting in which daily caloric intake is constrained to a consistent window of 8–12 hours without explicitly reducing total caloric intake. In young male mice, time-restricted feeding (TRF) reduces cancer risk by preventing obesity and metabolic diseases. TRF has also been shown to reduce breast cancer xenograft progression in obese mice. In humans, short-term clinical studies of TRE have revealed metabolic improvements that predict reduced cancer risk, and epidemiological evidence suggests that prolonged nightly fasting can reduce the risk of cancer, independent of changes in body weight. This promising preliminary evidence suggests that TRE may be an effective intervention for reducing cancer risk. However, the effects of TRF in aged animals and in the context of an obesogenic Western diet have not yet been established, and the mechanisms by which TRF reduces cancer risk remain unknown. This application builds upon promising preliminary data and leverages the complementary skills of the research team to address these critical gaps in knowledge. Both obesity and aging are associated with mitochondrial dysfunction and the production of pro-tumorigenic mitochondrial metabolites. Proposed experiments test the hypothesis that TRF optimizes mitochondria function through both cell-autonomous and systemic mechanisms, thereby reducing cancer risk. In Aim 1, the impact of TRF on mitochondria function and related physiologies will be established in aged mice. Nutrient metabolism, energy consumption, and mitochondria function will be assessed in these mice. In Aim 2, an innovative combination of metabolomics and mitochondria respiration assays will be used to test the impact of TRF on mitochondria function in normal and cancer cells (assessing both cell-autonomous and non-cell-autonomous mechanisms). The effects of TRF on tumor incidence will be assessed by subjecting tumor-prone mice to TRF. In Aim 3, plasma collected from a recently concluded human TRE intervention study will be used to test the effect of TRE on mitochondria function and cancer risk in humans. The proposed comparative analysis of TRE in humans and mice will provide critical mechanistic insight into how one form of intermittent fasting can help prevent cancer onset and improve treatment outcomes.


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 = $739,637 )
2025	2025	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	5	8/7/2025	NON-COMPETING CONTINUATION	$739,637
														Subtotal = $739,637

Issue Date FY: 2024 ( Subtotal = $702,656 )
2024	2024	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	4	8/20/2024	NON-COMPETING CONTINUATION	$702,656
														Subtotal = $702,656

Issue Date FY: 2023 ( Subtotal = $913,280 )
2023	2023	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	3	8/15/2023	NON-COMPETING CONTINUATION	$724,846
2023	2023	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	001	3	9/13/2023	SUPPLEMENT FOR EXPANSION	$188,434
														Subtotal = $913,280

Issue Date FY: 2022 ( Subtotal = $724,846 )
2022	2022	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	2	8/24/2022	NON-COMPETING CONTINUATION	$724,846
														Subtotal = $724,846

Issue Date FY: 2021 ( Subtotal = $762,137 )
2021	2021	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	1	8/20/2021	NEW	$762,137
														Subtotal = $762,137

Grand Total All Awards = $3,842,556

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Impact of Time-Restricted Feeding in Reducing Cancer Risk Through Optimizing Mitochondria Function

Award Number: R01CA258221

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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