# LOOH-induced muscle atrophy with age

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $536,291

## Abstract

Project Summary
Maintenance of skeletal muscle mass is essential for healthy aging and plays a significant role in quality of life.
Age-induced skeletal muscle atrophy (sarcopenia) not only reduces mobility but also increases the propensity
to develop metabolic and cardiovascular diseases. Although skeletal muscle atrophy has broad clinical impact
in the increasingly sedentary and aging population, a pharmacologic therapy for muscle mass loss does not
exist. Reactive oxygen species (ROS) likely induce muscle atrophy by accelerating proteolysis and depressing
protein synthesis. However, ROS refers to a collection of radical molecules whose cellular signals are vast,
and it is unclear which of the downstream consequences of oxidative stress are responsible for the loss of
muscle mass and function that occurs with age or disuse. In this application, we will test our hypothesis that
lipid ROS (LOOH) promotes muscle atrophy through accelerating autophagy/lysosome-dependent protein
degradation. 1) Cellular LOOH is neutralized by phospholipid hydroperoxidase (GPx4), preventing its
accumulation and degradation to form reactive lipid aldehydes. We will determine whether neutralization of
LOOH by N-acetylcarnosine treatment (lipid aldehyde scavenger) will suppress age and/or disuse-induced
skeletal muscle atrophy. 2) Suppression of polyunsaturated fatty acid (PUFA) incorporation by
lysophosphatidylcholine acyltransferase-3 (LPCAT3) inhibition prevents LOOH-induced cell death. We will
investigate whether LPCAT3 deletion can protect mice from muscle atrophy, and perform subcellular fluxomics
to examine intracellular fate of LPCAT3 product during oxidative stress. 3) GPx4 deletion increases protein
degradation by accelerating lysosomal degradation. We will test our hypothesis that LOOH supercharges
autophagic machinery by its lipidation with LC3.

## Key facts

- **NIH application ID:** 10382124
- **Project number:** 1R01AG074535-01A1
- **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:** 2022
- **Award amount:** $536,291
- **Award type:** 1
- **Project period:** 2022-02-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10382124

## Citation

> US National Institutes of Health, RePORTER application 10382124, LOOH-induced muscle atrophy with age (1R01AG074535-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10382124. Licensed CC0.

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