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Mechanism of mitochondria-induced myokine activation and implications for healthy aging.

Award Number: F31AG087692
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/25/2024
PERIOD OF PERFORMANCE END DATE: 06/24/2029

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Mechanism of mitochondria-induced myokine activation and implications for healthy aging. - PROJECT SUMMARY/ABSTRACT Excess body weight is a significant contributor to mortality rates in the United States, with class 2+ obesity increasing the risk of mortality by up to 91%. Physical activity plays a crucial role in managing prevalent diseases such as obesity, type 2 diabetes, and cardiovascular disease. Recently, exercise-stimulated myokines have been found to play a crucial role in inter-tissue signaling, promoting metabolic health and cardioprotection. However, the mechanism by which myokine expression is activated is poorly understood. Furthermore, therapeutically effective myokines are yet to be identified. Mitochondrial Precursor Overaccumulation Stress (mPOS) is a novel mediator of mitochondria-induced stress signaling, triggered by mitochondrial protein import stress and the accumulation of unimported mitochondrial proteins in the cytosol. In our preliminary study, we found the drastic activation of candidate myokines in a newly established mouse model of mPOS. This is accompanied with a strong lean phenotype and increased cardiac ejection fraction. These observations invited the hypothesis that mPOS may mediate myokine signaling, which ultimately promotes metabolic and cardiac health. In this predoctoral fellowship application, we will test the hypothesis that mitochondrial protein import stress can specifically induce myokine signaling by specific transcriptional factors in a bioenergetic-independent manner (Specific Aim 1). We will also test the hypothesis that mPOS-induced myokine release mediates fat loss and the improvement of cardiac health during aging (Specific Aim 2). Success of the proposed research represents a significant advancement in understanding mitochondria-induced myokine signaling and its potential implications for metabolic and cardiovascular health. Utilizing the murine and cell-based models, this study will uncover the mechanisms underlying myokine signaling and its impact on inter- tissue communication. These findings may lead to the discovery of novel health- promoting myokines and identification of therapeutic targets for metabolic and cardiovascular diseases, offering potential interventions to improve overall health, especially for aging populations and individuals unable to engage in physical exercise.


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: 2026 ( Subtotal = $55,114 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Aging Research	000	3	5/14/2026	NON-COMPETING CONTINUATION	$55,114
														Subtotal = $55,114

Issue Date FY: 2025 ( Subtotal = $54,538 )
2025	2025	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Aging Research	002	2	8/11/2025	NON-COMPETING CONTINUATION	$54,538
2025	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Aging Research	001	1	7/16/2025	OTHER REVISION	$0
2025	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Aging Research	000	1	5/28/2025	TERMINATION	$0
														Subtotal = $54,538

Issue Date FY: 2024 ( Subtotal = $53,974 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Aging Research	000	1	6/20/2024	NEW	$53,974
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Aging Research	001	1	6/20/2024	NEW	$0
														Subtotal = $53,974

Grand Total All Awards = $163,626

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Mechanism of mitochondria-induced myokine activation and implications for healthy aging.

Award Number: F31AG087692

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/25/2024

PERIOD OF PERFORMANCE END DATE: 06/24/2029

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