R01AG071676
Project Grant
Overview
Grant Description
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.
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.
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Virginia
United States
Geographic Scope
State-Wide
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 378% from $649,040 to $3,103,571.
Rector & Visitors Of The University Of Virginia was awarded
MG53 Myokine Therapy for Muscle Aging
Project Grant R01AG071676
worth $3,103,571
from National Institute on Aging in September 2022 with work to be completed primarily in Virginia United States.
The grant
has a duration of 4 years 9 months and
was awarded through assistance program 93.866 Aging Research.
The Project Grant was awarded through grant opportunity NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 6/22/26
Period of Performance
9/30/22
Start Date
6/30/27
End Date
Funding Split
$3.1M
Federal Obligation
$0.0
Non-Federal Obligation
$3.1M
Total Obligated
Activity Timeline
Subgrant Awards
Disclosed subgrants for R01AG071676
Transaction History
Modifications to R01AG071676
Additional Detail
Award ID FAIN
R01AG071676
SAI Number
R01AG071676-3007070865
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NN00 NIH National Insitute on Aging
Funding Office
75NN00 NIH National Insitute on Aging
Awardee UEI
JJG6HU8PA4S5
Awardee CAGE
9B982
Performance District
VA-90
Senators
Mark Warner
Timothy Kaine
Timothy Kaine
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute on Aging, National Institutes of Health, Health and Human Services (075-0843) | Health research and training | Grants, subsidies, and contributions (41.0) | $1,266,713 | 100% |
Modified: 6/22/26