Signaling pathways controlling skeletal muscle mass

Abstract

The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed “atrophy”, is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle.

• Cachexia
• IGF-1
• muscle atrophy
• muscle hypertrophy
• MuRF1
• myostatin
• sarcopenia
• skeletal muscle

Acknowledgements

We thank Mark Fishman, Michaela Kneissel, and the entire Muscle Group at the Novartis Institutes for Biomedical Research for their help and support. Thanks to Shou-Ih Hu, Jun Shi, and Mara Fornaro for critically reading the manuscript. Special thanks to Alan Abrams for generating the signaling figure.