Effects Of Skeletal Muscle Mitochondrial ROS And PGC-1α On Exercise To Improve Imflammaging

Objective:To observe ROS production, mitochondrial function and biosynthesis, expression of IL-6 and inflammatory factors involved in aging mice with a moderate-intensity endurance training intervention. This study aims to associate mitochondrial quality control system and myokines, reveal a new model of skeletal muscle mitochondria affect body functions, and explore mechanisms of skeletal muscle mitochondrial ROS and PGC-1α regulating IL-6 generated and body imflammatory level.Methods:120 male C57BL/6 mice were divided into 4-month,8-month and 15-month group, each group consist of control and training group. Eight weeks endurance training was implemented to training group before the prospective age. To determine ROS levels, mitochondrial respiratory function, expression of PGC-1 α, IL-6, NFκB, Nrf2 and TNF-α mRNA and protein by RT-PCR and Westernblot, serum concentration of IL-6 and TNF-α by ELISA in skeletal muscle and serum. C2C12 myoblasts were intervened by PGC-1 a siRNA and electrical stimulation after they differentiate into myotubes. Cells were divided into control group(C), electrical stimulation group(E), PGC-1α gene silencing group(P) and PGC-1α gene silencing+electrical stimulation group(PE). MDA, myotubes respiratory function, ROS, the genes and proteins were determined in the cells.Results:1. In the aging process, the skeletal muscle mitochondrial respiratory function decreased, ROS production and mitochondrial biogenesis increased, expression of IL-6 and TNF-a decreased; with endurance training, mitochondrial respiratory function improved, ROS levels and IL-6 and TNF-α basal levels significantly lower than the control group.2. In PGC-1α expression inhibited myotubes, respiratory function decreases, ROS increased and IL-6 expression rise. It had the highest TNF-α level in PE group, but IL-6 was less than E group.Conclusion:1. With aging process, mitochondrial function was decreasing, ROS was continuous in a high level, as well as PGC-1 a expression reduced, on the contrary, training provide transient or low-level ROS and improve expression of PGC-1a.2. PGC-1 a can improve mitochondrial function, increase mitochondrial biogenesis,withstand the high levels of ROS due to aging, thereby reduce NFκB expression and r the plasma level of IL-6 and TNF-α, to suppress the pro-inflammatory response. PGC-1α also promotes Nrf2 expression at the transcriptional level, thus contributing to the high levels of expression of IL-6 after exercise, and inhibition of TNF-α and anti-inflammatory.