Analysis of functional crosstalk between anabolic and catabolic pathway in skeletal muscle for the development of novel therapeutic strategies against sarcopenia

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09230
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: The University of Tokyo
• Principal Investigator: YOSHIKAWA NORITADA 東京大学, 医科学研究所, 講師 (70396878)
• Research Collaborator: TANAKA Hirotoshi ; SHIMIZU Noriaki ; YAMAZAKI Hiroki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: サルコペニア / 加齢 / 骨格筋 / 筋萎縮 / グルココルチコイド受容体 / mTOR / 蛋白質合成 / 蛋白質異化

Outline of Final Research Achievements

We hypothesized that sarcopenia is caused by resetting the set point defining the skeletal muscle mass and in which glucocorticoid receptor (GR) and mTOR play a critical role for the functional crosstalk between anabolic and catabolic pathway. In this line, for the development of novel therapeutic strategies against sarcopenia, we analyzed such a hypothesis by using skeletal muscle-specific GR KO mice, specific stimulators and inhibitors for the GR and mTOR, and multi-omics analysis.
We identified several molecular candidates which regulated the functional crosstalk between anabolic and catabolic pathway under the control of the GR and mTOR in skeletal muscle. We, thus, speculate that such molecules could be molecular targets for mitigating the development of sarcopenia and continue further analysis.

Free Research Field

内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究は、筋肥大と筋萎縮という機能的に拮抗する生体制御系が相互に関連しつつ筋量を制御する骨格筋固有の機構を解明し、サルコペニア治療法開発へ展開する挑戦的研究である。本研究成果は、サルコペニアの新規治療法開発のみならず、ステロイド-GR制御系のさらなる理解に基づくステロイド筋症治療法、また、糖尿病、慢性腎不全、慢性閉塞性肺疾患などの慢性疾患、癌悪液質、飢餓、を原因とする筋萎縮治療にも斬新な方法論を提供することが予想される。さらに、骨格筋の生理的役割の理解を進展させ、骨格筋を起点とする多臓器連関による高次生体制御機構解明のブレークスルーともなると考えられる。