Repeated Disuse Atrophy Imprints a Molecular Memory in Skeletal Muscle: Transcriptional Resilience in Young Adults and Susceptibility in Aged Muscle - PubMed
4 hours ago
- #molecular memory
- #aging muscle
- #disuse atrophy
- Repeated disuse atrophy creates a molecular memory in skeletal muscle, affecting transcriptional responses differently in young and aged individuals.
- Young muscle shows transcriptional resilience with attenuated oxidative and mitochondrial pathway disruptions despite atrophy.
- Aged muscle exhibits a detrimental memory, leading to greater atrophy, suppressed aerobic metabolism genes, and NAD+ depletion.
- DNA hypermethylation and downregulation of aerobic metabolism genes occur across species with repeated disuse.
- NR4A1 and NR4A3 genes are strongly suppressed by disuse, with NR4A1 remaining repressed due to hypermethylation.
- Acetylcholine receptor genes (CHRNA1, CHRND, CHRNG) are epigenetically primed and upregulated after disuse.
- NMRK2, an NAD+ biosynthesis gene, is significantly downregulated; nicotinamide riboside (NR) supplementation improves myotube size.
- Aged rats fail to recover muscle mass after disuse, unlike young rats.
- The study integrates physiological, multi-omic, and cellular analyses to explore disuse atrophy mechanisms.