Convergent Early Dysregulation of Sarcopenia-Associated Genes in Skeletal Muscle During Aging and SOD1G93A ALS Models

Skeletal muscle undergoes structural and functional decline due to aging and neuromuscular disorders such as amyotrophic lateral sclerosis (ALS), both of which impact protein expression and contribute to muscle atrophy. This study investigates how aging and the SOD1G93A ALS-related mutation affect the expression of eight genes previously linked to sarcopenia (PF4, OIT3, MMRN1, MASP1, C1R, SVEP1, VCAN and SPTB) but not yet characterized in muscle tissue. To this end, we analyzed their expression (1) during muscle aging in WT mice (5 and 24 months), (2) in SOD1G93A-transfected myotube cells in vitro, (3) in a muscle-specific SOD1G93A mouse model (5 and 24 months), and (4) in a systemic SOD1G93A transgenic mouse at different disease stages (60 and 120 days) by quantitative PCR. All eight target genes were expressed in skeletal muscle and most of them showed increased transcription with aging. In ALS models, gene expression was significantly overexpressed at early stages, particularly in muscle-specific (MLC/SOD1G93A) and systemic (SOD1G93A) models, mimicking aging-related profiles. These alterations attenuated with disease progression, suggesting an early transient muscle response to ALS-linked SOD1 mutations. Hence, this study demonstrates that sarcopenia-associated proteins are actively expressed and modulated in skeletal muscle during aging and ALS and suggests convergent response mechanisms.