Wednesday, August 20, 2025 8/20/2025

MG53 function in muscle aging

Award Number: R01AG071676
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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MG53 function in muscle aging - PROJECT SUMMARY Elderly persons are susceptible to injury with compromised regenerative capacity of the skeletal muscle, leading to gradual muscle weakness and loss of physical activity. Impaired myogenic satellite cell function is associated with muscle aging. While it is known that exercise has many beneficial effects on aging and can improve satellite cell function, searching for the putative myogenic factors that facilitate exercise-mediated improvement of muscle function presents an attractive area for geriatric research. We know that exercise induces secretion of MG53 from skeletal muscle into circulation, which serves as a myokine to protect multiple tissues from injuries. However, exercise-induced MG53 release is severely attenuated in aging. Chronic oxidative stress associated with aging leads to MG53 aggregation that compromises MG53’s function in tissue repair and regeneration. We hypothesize rejuvenating MG53’s myokine function will have benefits to aging. We have produced a transgenic mouse model with sustained elevation of MG53 in the bloodstream, and found that these mice display remarkable muscle regeneration following injury. We have data to show that treatment with recombinant human MG53 (rhMG53) protein promotes proliferation and protects against stress-induced injury to muscle satellite cells. Therefore, we propose to test if improvement of muscle satellite cell function by MG53 can provide long-term benefits to muscle aging. Chronic oxidative stress and inflammation associated with aging may cause tissue injury and consequently the elevation of MG53 in circulation. We will use a combination of live cell imaging, proteomic, and CRISPR-gene editing tools to test if post-translational modification of MG53 in the serum can be a contributing factor for MG53’s compromised tissue repair function during aging. Outcomes of the studies in this project can lay the foundation and pave the way for our long-term goal of translating the basic findings of the benefits of MG53 into therapeutic treatments of age-related muscle dysfunctions.


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 = $604,073 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	4	7/30/2025	NON-COMPETING CONTINUATION	$604,073
														Subtotal = $604,073

Issue Date FY: 2024 ( Subtotal = $617,042 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	3	7/2/2024	NON-COMPETING CONTINUATION	$617,042
														Subtotal = $617,042

Issue Date FY: 2023 ( Subtotal = $617,673 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	001	2	7/7/2023	NON-COMPETING CONTINUATION	$617,673
2023	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	1	2/14/2023	NEW	$0
														Subtotal = $617,673

Issue Date FY: 2022 ( Subtotal = $649,040 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	1	9/16/2022	NEW	$649,040
														Subtotal = $649,040

Grand Total All Awards = $2,487,828

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MG53 function in muscle aging

Award Number: R01AG071676

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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