Study Highlights Skeletal Muscle Changes During Disuse and Rehabilitation
A recent study from the lab of Blake Rasmussen, PhD, and published in Physiological Reports examined how short-term skeletal muscle disuse and subsequent rehabilitation affect muscle function and gene expression in healthy middle-aged adults. Participants underwent seven days of unilateral lower-limb suspension followed by a two-week rehabilitation period that included either resistance exercise or walking. Muscle strength declined after disuse, accompanied by coordinated transcriptomic changes marked by reduced expression of genes involved in mitochondrial function and cellular respiration, alongside increased inflammatory and apoptotic signaling.
During rehabilitation, resistance exercise induced substantially greater molecular and functional recovery than walking, reversing many of the disuse-associated gene expression changes and supporting improvements in muscle strength. These findings provide insight into the biological pathways underlying muscle plasticity in midlife and highlight the importance of targeted resistance training to mitigate the effects of inactivity and support muscle health with aging.
Key takeaways:
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Seven days of limb immobilization led to measurable losses in muscle strength and widespread transcriptomic changes affecting energy metabolism, inflammation, and cell survival pathways.
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Resistance exercise during rehabilitation reversed many disuse-associated gene expression changes and supported superior strength recovery compared with walking.
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The findings underscore the importance of targeted resistance training to counteract inactivity-related muscle decline and promote healthy aging.
Dr. Rasmussen is Professor and Chair of the Department of Cellular & Integrative Physiology at UT Health San Antonio and an investigator at the Sam and Ann Barshop Institute for Longevity and Aging Studies.
Transcriptomic time course of skeletal muscle disuse and rehabilitation in middle-aged adults
Zachary D Von Ruff, Sean P Kilroe, Erik D Marchant, Emily J Arentson-Lantz, Steven Widen, Jill Thompson, Alejandro Villasante-Tezanos, Elena Volpi, Doug Paddon-Jones, Blake B Rasmussen
Physiol Rep. 2025 Aug;13(15):e70497. doi: 10.14814/phy2.70497.
Abstract:
Disuse drives rapid muscle atrophy and metabolic dysfunction. This study aimed to characterize phenotypic and transcriptomic skeletal muscle changes in middle-aged individuals during disuse and rehabilitation. Eleven healthy middle-aged adults (6 males, 5 females; age; 57 ± 5 years) underwent 7 days of unilateral lower limb suspension (ULLS). Following disuse, participants participated in a rehabilitation program consisting of either a lower-body resistance exercise (RE) or walking control (WC) three times weekly for 2 weeks. Bilateral skeletal muscle biopsies were collected at Day 0 and Day 7 of disuse and 2 h post-exercise on Days 7, 9, 11, and 21. Strength testing was conducted, and RNA sequencing was performed on muscle samples. Seven days of disuse reduced knee extension strength (14%; p < 0.05) and isometric force (13%; p < 0.05). Over-representation analysis revealed a downregulation of mRNAs related to cellular respiration and NADH dehydrogenase complex assembly. Resistance exercise induced robust, but different, transcriptional changes in both disuse- and control-legs. Walking had minimal effect on the muscle transcriptome. We conclude that 7 days of disuse reduced leg strength, decreased mitochondrial gene expression, and increased inflammation and apoptosis-related genes. We also conclude that resistance exercise enhanced recovery from disuse by improving strength, associated with significant transcriptomic changes.
Keywords: aging; disuse atrophy; resistance exercise; transcriptomics.