Mechanisms of Skeletal Muscle Atrophy and Molecular Circuitry of Stem Cell Fate in Skeletal Muscle Regeneration and Aging

Skeletal muscle is a complex and highly adaptable tissue. With aging, there is a progressive loss of muscle mass and function, known as sarcopenia, and a reduced capacity for regeneration and repair following injury. A review of the literature shows that the primary mechanisms underlying the age-related loss of muscle mass and the attenuated growth response are multi-factorial and related to alterations in multiple processes, including proteostasis, mitochondrial function, extracellular matrix remodeling, and neuromuscular junction function. Multiple factors influence the rate of sarcopenia, including acute illness and trauma, followed by incomplete recovery and repair. Regeneration and repair of damaged skeletal muscle involve an orchestrated cross-talk between multiple cell populations, including satellite cells, immune cells, and fibro-adipogenic precursor cells. Proof-of-concept studies in mice have demonstrated that reprogramming of this disrupted orchestration, resulting in the normalization of muscle function, may be possible using small molecules that target muscle macrophages. During aging, as well as in muscular dystrophies, disruptions in multiple signaling pathways and in the cross-talk between different cell populations contribute to the failure to properly repair and maintain muscle mass and function.

Automated summary

Skeletal muscle undergoes significant changes with aging, leading to a loss of muscle mass and function. This is caused by various factors including alterations in proteostasis, mitochondrial function, extracellular matrix remodeling, and neuromuscular junction function. Factors such as acute illness and trauma contribute to the rate of sarcopenia. Repair and regeneration of skeletal muscle involve coordination between different cell populations, and targeting muscle macrophages with small molecules has shown promise in restoring muscle function. Disruptions in signaling pathways and cell communication contribute to the failure to repair and maintain muscle mass and function in aging and muscular dystrophies.