# Regulation of macrophage metabolism in aged muscle during recovery

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $622,642

## Abstract

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 mechanism 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-1α and accumulation of TCA intermediates
such as succinate. Our preliminary data in impaired aged muscle during early recovery supports decreased
macrophage succinate and HIF-1α 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-1α 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).

## Key facts

- **NIH application ID:** 10834086
- **Project number:** 5R01AG076075-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Micah J Drummond
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $622,642
- **Award type:** 5
- **Project period:** 2022-05-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834086

## Citation

> US National Institutes of Health, RePORTER application 10834086, Regulation of macrophage metabolism in aged muscle during recovery (5R01AG076075-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10834086. Licensed CC0.

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