Non-regenerative myogenesis in adult skeletal muscles: myofiber death-independent muscle satellite cell expansion

Muscle regeneration processes triggered by injuries following myofiber death have been extensively investigated owing to the availability of suitable in vivo animal models, including disease models. During muscle regeneration, skeletal muscle-resident stem cells, also known as muscle satellite cells (MuSCs), exit the quiescent state, become activated, and proliferate to generate new myofibers. These MuSC behaviors have also been observed in resistance- and endurance-training models. In these models, MuSC behaviors are thought to follow the same mechanisms as myogenesis observed during regeneration (regenerative myogenesis), as certain animal training models induce myofiber death; moreover, myofiber damage markers have been detected in human training samples. Nevertheless, accumulating evidence suggests that MuSCs can become activated, proliferate, and differentiate in the absence of overt signs of myofiber death. Considering the therapeutic potential of MuSCs for muscle atrophy, injury-independent myogenesis (non-regenerative myogenesis) must be investigated, as apparent and frequent myofiber death does not occur in many atrophic conditions. In this review, we introduce the concept and evidence for “non-regenerative myogenesis” in adult skeletal muscle and highlight its characteristics and the remaining research questions.