Role of Fyn and the interleukin-6-STAT-3-autophagy axis in sarcopenia

Abstract

Sarcopenia is the progressive loss of muscle mass wherein Fyn regulates STAT3 to decrease autophagy. To elucidate the role of inflammation in Fyn-STAT3-dependent autophagy and sarcopenia, here we aimed to investigate the underlying mechanisms using two mouse models of primary and secondary sarcopenia: (1) tail suspension and (2) sciatic denervation. In wild-type mice, the expression of Fyn and IL-6 increased significantly. The expression and phosphorylation levels of STAT3 were also significantly augmented, while autophagic activity was abolished. To investigate Fyn-dependency, we used tail suspension with Fyn-null mice. In tail-suspended wild-type mice, IL-6 expression was increased; however, it was abolished in Fyn-null mice, which maintained autophagy and the expression and ablation of STAT3 phosphorylation. In conclusion, Fyn was found to be associated with the IL-6-STAT3-autophagy axis in sarcopenia. This finding permits a better understanding of sarcopenia-associated metabolic diseases and the possible development of therapeutic interventions.