Circadian Rhythms and their affect on Skeletal muscles

 In Dr. Cavanaugh's talk about his paper " The cell-intrinsic circadian clock is dispensable for lateral posterior clock neuron regulation of Drosophila rest-activity rhythms", he references how there are genes that regulate our circadian clock. It is a negative feedback loop where the activation of CLK and CYC induce the production of TIM and PER genes. these genes get made into RNA, leave the nucleus, get turned into proteins, go back into the cell and turn off the production of the RNA. These genes are the ones that are used in the fruit fly, but in humans they use CRY and BMAL instead of CYC and TIM. Dr. Cavanaugh also shows us the SCN, which in mammals is where the circadian clock's rhythmicity is regulated. If it is cut or removed there would be no rhythmicity. He also talked about the fact that almost all cells in the body exhibit some form of rhythmicity, and with that in mind it would make sense that the circadian rhythm is important for muscle growth as well, and the lack of rhythmicity would be detrimental, and that is exactly what the paper "The Role of the Molecular Clock in Promoting Skeletal Muscle Growth and Protecting against Sarcopenia" by Jacopo A Vitale showed.

When looking at the significance of clock genes to skeletal muscles, they decided to use knock out mice and knock out BMAL. They saw that  at 9 months of age, the mice decreased in about half of a normal mouse's body weight, and it indicated a premature aging phenotype. This shows how important the circadian clock is in maintaining skeletal muscles. But how does it affect muscle growth? In humans it has been shown that human muscle torque, strength, and power are higher in the late afternoon. However, while the circadian clock does matter and there are time of day that are more important for working out than others, there is are ways to manipulate them. These would be environmental factors or zeitgebers such as hormonal changes, variations in body temperature, and scheduled exercise. These factors could change the time in which the muscle clock fires. Not only is this important for exercise, but also for metabolism. The paper also explores how BMAL is necessary for skeletal muscle metabolism as about 35% percent of the rhythmic genes in skeletal muscles are involved in metabolism. They did another experiment where they tested the function of BMAL in skeletal muscles, and they did this by doing another knock out mouse. They found that the mice that had this knock out were leading to an altered insulin dependent glucose uptake and a glucose oxidation reduction. This showed that there would be issues without the rhythmicity of skeletal muscles. 

In conclusion, this paper in tandem with Dr.Cavanaugh’s paper show just how important circadian rhythms are to our overall health. To increase our muscle mass we have to sleep well, eat well, and respect the circadian rhythm.

Vitale JA, Bonato M, La Torre A, Banfiu G. The Role of the Molecular Clock in Promoting Skeletal Muscle Growth and Protecting against Sarcopenia. Int J Mol Sci. 2019 Sep 3;20(17):4318. doi: 10.3390/ijms20174318. PMID: 31484440; PMCID: PMC6747101.