R01AG076075
Project Grant
Overview
Grant Description
Regulation of Macrophage Metabolism in Aged Muscle During Recovery - Abstract
Muscle regrowth and function following disuse atrophy in aged muscle is significantly compromised, and this increases the risk for falls, long-term disability, and loss of independence. Therapeutic strategies to enhance muscle recovery are non-existent stemming from a poor understanding of cellular mechanisms during regrowth in aging muscle.
Invasion of muscle macrophages and polarization to pro- and anti-inflammatory states are critical to promote muscle stem cell function and the full resolution of muscle and function following disuse. More recently, macrophage metabolism has been shown to be tightly coupled to the inflammatory state of activated macrophages and regulated by transcription factors such as HIF-1A and accumulation of TCA intermediates such as succinate.
Our preliminary data in impaired aged muscle during early recovery supports decreased macrophage succinate and HIF-1A corresponding to a reduced macrophage glycolytic and inflammatory program and functional characteristics. Therefore, using novel mouse genetic and bone marrow transfer experiments, along with chemical approaches and in vitro studies, we will test if succinate and HIF-1A are key regulatory steps for macrophage metabolic and inflammatory activation during regrowth from disuse in aging muscle and if this dysfunction arises from an aged immune system.
In Aim 2, we will translate our pre-clinical findings to young and older humans and confirm our hypothesis by extensively characterizing muscle macrophage metabolic and inflammatory functional states in vivo and in vitro during recovery from disuse atrophy. We anticipate that the findings will identify macrophage metabolism as a future target to accelerate the recovery of aged muscle following disuse-related events (e.g., surgery, illness).
Muscle regrowth and function following disuse atrophy in aged muscle is significantly compromised, and this increases the risk for falls, long-term disability, and loss of independence. Therapeutic strategies to enhance muscle recovery are non-existent stemming from a poor understanding of cellular mechanisms during regrowth in aging muscle.
Invasion of muscle macrophages and polarization to pro- and anti-inflammatory states are critical to promote muscle stem cell function and the full resolution of muscle and function following disuse. More recently, macrophage metabolism has been shown to be tightly coupled to the inflammatory state of activated macrophages and regulated by transcription factors such as HIF-1A and accumulation of TCA intermediates such as succinate.
Our preliminary data in impaired aged muscle during early recovery supports decreased macrophage succinate and HIF-1A corresponding to a reduced macrophage glycolytic and inflammatory program and functional characteristics. Therefore, using novel mouse genetic and bone marrow transfer experiments, along with chemical approaches and in vitro studies, we will test if succinate and HIF-1A are key regulatory steps for macrophage metabolic and inflammatory activation during regrowth from disuse in aging muscle and if this dysfunction arises from an aged immune system.
In Aim 2, we will translate our pre-clinical findings to young and older humans and confirm our hypothesis by extensively characterizing muscle macrophage metabolic and inflammatory functional states in vivo and in vitro during recovery from disuse atrophy. We anticipate that the findings will identify macrophage metabolism as a future target to accelerate the recovery of aged muscle following disuse-related events (e.g., surgery, illness).
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Salt Lake City,
Utah
841125339
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 421% from $626,914 to $3,264,844.
University Of Utah was awarded
Enhancing Aged Muscle Recovery: Targeting Macrophage Metabolism
Project Grant R01AG076075
worth $3,264,844
from National Institute on Aging in May 2022 with work to be completed primarily in Salt Lake City Utah United States.
The grant
has a duration of 5 years and
was awarded through assistance program 93.866 Aging Research.
The Project Grant was awarded through grant opportunity Research Project Grant (Parent R01 Clinical Trial Required).
Status
(Ongoing)
Last Modified 5/21/26
Period of Performance
5/15/22
Start Date
4/30/27
End Date
Funding Split
$3.3M
Federal Obligation
$0.0
Non-Federal Obligation
$3.3M
Total Obligated
Activity Timeline
Transaction History
Modifications to R01AG076075
Additional Detail
Award ID FAIN
R01AG076075
SAI Number
R01AG076075-2686768075
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
LL8GLEVH6MG3
Awardee CAGE
3T624
Performance District
UT-01
Senators
Mike Lee
Mitt Romney
Mitt Romney
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) | $1,249,220 | 100% |
Modified: 5/21/26