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Treatment strategy to enhance Nrf2 signaling in older adults: combining acute exercise with the phytochemical sulforaphane

Award Number: R15AG074088
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Treatment strategy to enhance Nrf2 signaling in older adults: combining acute exercise with the phytochemical sulforaphane - PROJECT SUMMARY: Redox balance plays a key role in the age-associated increased risk for diseases. One reason for the lower resistance to oxidative stress with age is a gradual shift in the redox state toward a more oxidized cellular environment resulting in disruption of cell signaling. Nuclear erythroid factor 2-related factor 2 (Nrf2) is the master regulator of antioxidant defenses. Nrf2 drives expression of a host of genes involved in cytoprotection and antioxidant defenses. Our lab was the first to demonstrate Nrf2 activation in response to acute exercise in humans, and in agreement with animal data, we found an age-related impairment in exercise-induced Nrf2 signaling. This underscores an important problem related to aging, namely that older individuals are less sensitive to an exercise stimulus compared to younger cohorts. The focus of the proposed study is to try to solve this problem by amplifying the signal and mitigating the “exercise desensitization” exhibited by older individuals to restore redox balance. This study will test the hypothesis that combining acute exercise with sulforaphane will improve Nrf2 activation and downstream signaling in older adults compared to either alone. Sulforaphane is a phytonutrient found in high concentrations in cruciferous vegetables and a potent Nrf2 activator. The hypothesis will be tested using two different approaches; the first experiment will use an in vivo–ex vivo approach, where peripheral blood mononuclear cells (PBMCs) collected from older men and women (≥60y, n=30) pre- and post-acute exercise (in vivo) will be cultured and stimulated with SFN (ex vivo). This allows for a greater experimental control of the SFN stimulus. The second experiment will test the clinical translation applying the sulforaphane stimulus in vivo through an oral supplementation of sulforaphane in the form of whole broccoli sprout material, prior to acute exercise, in the same individuals. This second experiment will be a randomized placebo-controlled cross-over design. For all trials Nrf2 signaling will be measured by Nrf2 activation through an ARE binding assay, nuclear to whole cell ratio of Nrf2 protein, and Nrf2-dependent gene expression (HO-1, GCLC, NQO1, GR). Potential sex differences will be investigated. The insights gained from this study are whether combining simple interventions in the category of healthy lifestyle and preventive medicine can improve the adaptive response to exercise in older individuals. This could have an enormous impact by improving the health and well-being of older Americans, an important mission of the National Institutes of 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 = -$20,032 )
2025	2022	NORTHERN ARIZONA UNIVERSITY	601 S KNOLES DR RM 220	FLAGSTAFF	AZ	86011	COCONINO	USA	Aging Research	000	1	9/4/2025	NEW	-$20,032
														Subtotal = -$20,032

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	NORTHERN ARIZONA UNIVERSITY	601 S KNOLES DR RM 220	FLAGSTAFF	AZ	86011	COCONINO	USA	Aging Research	000	1	4/25/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $448,752 )
2022	2022	NORTHERN ARIZONA UNIVERSITY	601 S KNOLES DR ROOM 220	FLAGSTAFF	AZ	86011	COCONINO	USA	Aging Research	000	1	5/31/2022	NEW	$448,752
														Subtotal = $448,752

Grand Total All Awards = $428,720

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Treatment strategy to enhance Nrf2 signaling in older adults: combining acute exercise with the phytochemical sulforaphane

Award Number: R15AG074088

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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