An integrative transcriptomic atlas of ALS and aging skeletal muscle defines shared and distinct molecular programs of degeneration.

Early-stage ALS muscle exhibits molecular features of aged muscle, suggesting premature aging in ALS skeletal muscle.

• Why it matters: Understanding the molecular differences and similarities between ALS and aging muscle can reveal shared pathways and unique mechanisms, aiding targeted therapies.
• What they did: Using the SOD1 G93A ALS mouse model and wild-type mice across their lifespan, an integrated single-nucleus transcriptomic atlas of skeletal muscle was generated, including structural and functional analyses.
• The result: The atlas identified condition-specific myonuclear states, with ALS muscle showing early molecular hallmarks of aging and a distinct ALS-enriched myonuclei subpopulation, highlighting potential therapeutic targets.