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

Tsuyoshi Sasaki; Eijiro Yamada; Ryota Uehara; Shuichi Okada; Hirotaka Chikuda; Masanobu Yamada

doi:10.1016/j.isci.2023.107717

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

iScience. 2023 Aug 25;26(10):107717. doi: 10.1016/j.isci.2023.107717. eCollection 2023 Oct 20.

Authors

Tsuyoshi Sasaki¹, Eijiro Yamada², Ryota Uehara², Shuichi Okada², Hirotaka Chikuda¹, Masanobu Yamada²

Affiliations

¹ Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan.
² Department of Internal Medicine, Division of Endocrinology and Metabolism, Gunma University Graduate School of Medicine, Maebashi, Japan.

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.

Keywords: Biological sciences; Disease.