Myostatin Signaling Review Integrates Myogenesis, Genetic Polymorphisms, and Therapeutic Modulation for Athletic Performance

Skeletal muscle growth and homeostasis are critically regulated by myostatin, a negative regulator encoded by the MSTN gene. Current understanding highlights its influence on satellite cell proliferation, differentiation, and protein synthesis via Smad-dependent and non-Smad pathways. Dysregulation of myostatin, such as overexpression, leads to muscle atrophy and impaired recovery, while reduced activity boosts protein synthesis and regeneration, primarily through the IGF-1/Akt/mTOR signaling pathway. Modulating myostatin offers potential benefits for metabolic function, insulin sensitivity, and musculoskeletal adaptation, addressing gaps in optimizing athletic performance and muscle health.

This comprehensive review synthesized existing literature on myostatin's multifaceted roles in skeletal muscle. Researchers systematically evaluated studies covering myogenesis, MSTN-mediated signaling pathways, genetic polymorphisms, endocrine interactions, and therapeutic modulation strategies. The primary objective was to provide an integrated overview of these areas, discussing their implications for muscle hypertrophy, inflammation, and sports performance. The review also identified future research directions in precision sports genomics and translational muscle biology, highlighting areas where current understanding remains limited despite extensive research.

The review established myostatin as a crucial negative regulator of skeletal muscle growth, influencing satellite cell proliferation, differentiation, and protein synthesis. It elucidated that myostatin acts through both Smad-dependent and non-Smad signaling pathways. > Reduced myostatin activity consistently enhances protein synthesis and muscle regeneration, primarily by modulating the IGF-1/Akt/mTOR signaling pathway. Genetic variations in the MSTN gene and its receptors, ACVR2A and ACVR2B, significantly contribute to inter-individual differences in muscle morphology, fiber-type distribution, and athletic performance. Specifically, polymorphisms like rs1805086 and rs11333758 were associated with variations in muscle strength, hypertrophy, and endurance capacity. Furthermore, myostatin modulation was linked to improved metabolic function, increased insulin sensitivity, and enhanced musculoskeletal adaptation, suggesting broad physiological impacts beyond just muscle mass.