Speaker Dr Jeffrey Kelu, Postdoctoral Research Associate, Hughes Lab, Randall Centre, KCL

Title An intrinsic timekeeping mechanism in muscle controls growth and homeostasis

Host Simon Hughes and Fiona Wardle

 

Abstract Skeletal muscle shows significant time-of-day variations in physiology and metabolism, such as the increase in muscle strength from morning to evening in humans. However, whether muscle growth also varies with time-of-day remains unclear. By tracking live zebrafish larvae over circadian cycles, we demonstrate that muscle grows faster during the day than at night under constant conditions, independent of physical activity and feeding rhythms. This circadian regulation of muscle growth is supported by higher protein synthesis rates during the day and increased protein degradation at night. Disruption of the molecular clock in the muscle eliminates the circadian muscle growth difference, indicating the cell-autonomous role of the muscle clock. Mechanistically, proteasome- and autophagy-mediated protein degradation are suppressed at night when the muscle clock is perturbed, due to reduced MuRF abundance and elevated TORC1 activity, respectively. Fish lacking a functional muscle clock develop sarcopenia (reduced muscle mass and function) prematurely. Therefore, the muscle clock is crucial for maintaining muscle homeostasis and growth through the circadian regulation of protein turnover. Our study provides insights into how chronic circadian misalignments, such as shift work, may lead to muscle mass and strength loss, and help develop strategies to optimise muscle health and performance through circadian biology.