Circadian rhythms in muscle health and diseases

All major life forms from bacteria to humans have internal clocks that regulate essential biological processes in a roughly 24-h cycle. In mammals, the central clock in the suprachiasmatic nucleus (SCN) is historically considered the top of a hierarchical organisation that dominates subordinate clocks in peripheral tissues and dictates the circadian behaviours of an organism. Recent studies, however, underscore the importance of the local circadian oscillators, such as the skeletal muscle clock, in regulating local metabolism and physiology. Studies in animal models show that the muscle peripheral clock per se is required for the expression of genes involved in glucose, lipid, and amino acid metabolism. Disruption of the muscle clock leads to glucose intolerance, insulin resistance, and alterations in muscle size and force. This highlights the vital role of the muscle clock in controlling muscle physiology and metabolism. In humans, a perturbation in the muscle circadian rhythms is seen in metabolic disorders such as type 2 diabetes, and muscle diseases such as dystrophies. Disruption of muscle metabolism is also seen when the internal rhythms are misaligned with the external rhythms (circadian misalignments) as in shift work. Understanding the mechanisms by which the muscle clock regulates circadian functions may help the development of new strategies, such as chronotherapy, to potentially prevent or treat muscle pathologies and maintain muscle health.