Clock-Mediated Rhythms and Phase Shifts in Skeletal Muscle Through Transcriptional-Translational Feedback Loops: Effects of Exercise

Paul Hwang, Darryn Willoughby


The circadian clock, which composites an autoregulatory transcriptional-translational feedback loop to mediate diurnal oscillations is regulated by the transcription factors, CLOCK and BMAL1, and their respective target genes; Per1, Per2, Cry1, and Cry2. Connections between the molecular clock and intracellular signaling pathway markers in skeletal muscle have been discovered, suggesting that metabolic sensors, such as AMPK and PGC1α, constitute overlapping modulation within the molecular clock involved in regulating skeletal muscle metabolism in response to nutrient availability, muscle contraction, energy balance, and redox status. A greater understanding of the mechanisms underlying these core clock components may potentially provide insights into the development of therapeutic interventions against metabolic disorders or methodologically incur a paradigmatic shift in exercise training to improve exercise performance. Furthermore, implications from these time-of-day studies may be generalizable to encourage temporal specificity in exercise training programs, whether it involves cardiovascular exercise or resistance training. However, there is a paucity of research investigating whether the circadian expression and translation of core clock components may underlie muscle protein accretion and subsequent exercise performance outcomes. Moreover, with the continuous emergent research discoveries upon the functions of the skeletal muscle clock, it is conceivable that interventions targeting the myogenic-mediating activities of the molecular clock can be established to generate novel approaches for not only improving adaptations to exercise training, but also in preventing and treating muscle-wasting diseases such as sarcopenia. Therefore, additional studies attempting to elucidate mechanisms that underlie circadian clock function and subsequent mediation in skeletal muscle during exercise warrants further research.


chronobiology; circadian rhythm, clock genes; signaling sensors; skeletal muscle; exercise performance


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Cell Mol Exerc Physiol (CMEP) Online ISSN: 2049-419X Prefix DOI: 10.7457