The multifaceted role of MyoD in adult skeletal muscle: homeostasis, regeneration, and diseases

Myogenic regulatory factors, including myoblast determination protein 1 (MyoD1 or MyoD) and myogenic factor 5 (Myf5), crucially regulate skeletal muscle lineage specification and development. Although MyoD and Myf5 exhibit overlapping functions during embryogenesis, their roles significantly diverge in adult muscles. Single MyoD knockout analysis revealed that MyoD uniquely regulates adult muscle regeneration, considerably influencing delayed myogenic differentiation, enhancing self-renewal, and modulating apoptosis resistance. These findings highlight fundamental differences between embryonic and adult myogenesis. Recent advances in single-cell technologies have revealed the heterogeneity of MyoD expression among adult muscle stem cells (MuSCs), thereby elucidating its diverse functional roles during muscle regeneration. Furthermore, MyoD has been implicated in the regulation of myofiber type specification and plasticity in mature skeletal muscles. Overall, these findings suggest that MyoD serves as a key orchestrator in cellular, functional, and pathological processes in adult skeletal muscle across multiple contexts. Although previous reviews have extensively addressed the role of MyoD in embryonic muscle development, the available literature lacks a focused discussion on its multifaceted functions in adult MuSCs, mature myofibers, and the aging process. In this review, we aimed to bridge this gap by integrating recent discoveries and offering novel insights into the dynamic roles of MyoD in adult skeletal muscles; the information discussed in this review has potential therapeutic implications in muscle regeneration, disease management, and combating age-related muscle decline.