Impact And Mechanism Of Intermittent Fasting On Myocyte Renewal

Background and aims: Skeletal muscle is the basic component of the motor system and an important regulator of body metabolism.Skeletal muscle is one of the most prominent degenerative tissues during aging,which typical phenotype is sarcopenia,that is,the gradual loss of skeletal muscle mass and function with aging.However,effective strategies for improving sarcopenia are still very limited.Studies have shown that intermittent fasting can systematically promote autophagy,improve the aging phenotypes,and even prolong animal life.This paper explores whether intermittent fasting has an effect on myocyte renewal.In addition,considering the important role of autophagy in tissue and cell renewal,we also explore whether intermittent fasting affects myocyte renewal through autophagy.Methods: The mice were treated with every-other-day fasting(EODF)and acute fasting to explore their effects on skeletal muscle cell renewal.In addition,biochemical analysis and transcriptomic analysis were used to explore the potential mechanisms of intermittent fasting on myocyte renewal.Results: After intermittent fasting treatment in mice,the expression of proliferation marker Ki-67 in muscle tissue was increased and the myogenic factor genes Myf6 and MyhcⅡa were up-regulated;the LysoTracker Red labeled lysosome in muscle tissue was significantlyup-regulated,and the expressions of autophagy-related genes Atg7 and Lamp2 were up-regulated.In contrast,the treatment of acute fasting 24 h led to an extremely significant up-regulation of two key factors of muscle atrophy,Murf-1 and Atrogin-1.In the treatment of refeeding 24 h after acute fasting,the expressions of Murf-1 and Atrogin-1 were significantly down-regulated,and the expressions of myogenic factor Myog and Musk were significantly up-regulated.These results suggest that the cycle of fasting and refeeding may promote myocyte renewal.In addition,the results of transcriptomic studies showed that both acute fasting and intermittent fasting caused a large number of changes in autophagy-related genes expression,and gene set enrichment analysis(GSEA)also indicated that autophagy was significantly up-regulated.And further bioinformatics analysis showed that fasting mainly promotes autophagy through the FOXO and PI3K-AKT signaling pathways.Conclusions: Intermittent fasting can promote myocyte renewal,which is beneficial to improve muscle atrophy;the mechanism of intermittent fasting promoting myocyte renewal is closely related to the up-regulation of autophagy.