# Sex-specific determinants of early-phase recovery from skeletal muscle disuse

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $504,379

## Abstract

PROJECT SUMMARY .
Despite the well-characterized consequences of disuse, we have a limited understanding of the early changes
in the molecular environment that influence rehabilitation efforts in men and women. We propose a 2-phase,
randomized, clinical trial that includes 7-days of unilateral leg disuse (Phase 1), immediately followed by 14-
days of bilateral leg rehabilitation (Phase 2). We will recruit middle-aged men and women; a historically
neglected research demographic who present with a largely youthful phenotype, but are at risk of accelerated
disuse atrophy.
! In Phase 1, we will explore the sex-specific effects of skeletal muscle disuse and characterize subjects
 most-and least-susceptible to disuse atrophy. In male and female volunteers, single-leg muscle atrophy will
 be induced using an established knee-brace/disuse protocol. We will obtain skeletal muscle biopsies to
 characterize the sex-specific, molecular signature of skeletal muscle disuse, while highlighting differences
 in traditional morphologic and functional outcomes.
! In Phase 2, we will map the early molecular time-course of rehabilitation in men and women and determine
 if disused and healthy muscle respond similarly to an exercise / rehabilitation intervention. Sex-specific
 volunteer cohorts will complete: i) a structured bilateral, resistance-exercise rehabilitation protocol, or ii) a
 passive, ambulatory recovery (Control). We will obtain muscle biopsies after 0, 48, 96 h of rehabilitation to
 characterize the early time course of recovery of molecular transducers of disuse. These early, pre-clinical
 molecular changes will be supported by traditional morphologic, body composition and muscle function
outcomes.
This project will address critical knowledge gaps that limit the efficacy of current strategies to restore muscle
health following periods of disuse. Current strategies, while well intentioned, are largely inconsistent with the
practice of evidence-based medicine and place a financial and human resource burden on our health care
delivery system. By characterizing changes in the molecular, morphologic and functional landscape of skeletal
muscle during disuse and rehabilitation and reposing our RNASeq data within the Gene Expression Omnibus
(GEO) website, this study may serve as the foundation for future, targeted studies of skeletal muscle disuse in
clinical populations with comorbid conditions.

## Key facts

- **NIH application ID:** 10168427
- **Project number:** 5R01AG064386-03
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Blake B Rasmussen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $504,379
- **Award type:** 5
- **Project period:** 2019-08-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168427

## Citation

> US National Institutes of Health, RePORTER application 10168427, Sex-specific determinants of early-phase recovery from skeletal muscle disuse (5R01AG064386-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10168427. Licensed CC0.

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