著者

細田 隆介 久野 篤史 中島 龍汰 朝倉 聖大 岩原 直敏 野島 伊世里 國本 梨沙 堀尾 嘉幸

出版者

公益社団法人 日本薬理学会

雑誌

日本薬理学会年会要旨集 第95回日本薬理学会年会 (ISSN:24354953)

巻号頁・発行日

pp.2-YIA-44, 2022 (Released:2022-03-21)

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[Background] SIRT1, an NAD+-dependent deacetylase, positively regulates autophagy, which maintains muscle mass and declines with age. We previously reported that treatment with resveratrol (RSV), an activator of SIRT1, restores muscle autophagy and preserves muscle mass in a mouse model of Duchenne muscular dystrophy. We hypothesized that RSV attenuates age-related muscle atrophy by activating SIRT1 and autophagy.[Methods and Results] DDY mice were treated with either a control diet or a diet containing RSV (0.4 g/kg diet) from 23 weeks of age, and tissues of tibialis anterior muscle were analyzed at 60 weeks old. Rotarod running time was shortened with aging; however, RSV treatment preserved running time. RSV blocked the aging-related increase in acetylated lysine levels in muscles, suggesting that RSV restored deacetylase activity of muscle SIRT1. Compared with 20 weeks old mice, the myofiber diameter was decreased in untreated 60 weeks old mice. In addition, LC3-II/LC3-I ratio, a marker of autophagic activity, was decreased and p62 and ubiquitinated protein levels, which are degraded by autophagy, were increased in muscles of 60 weeks old mice, suggesting impaired autophagy by aging. RSV treatment preserved the myofiber diameter, increased LC3-II/LC3-I ratio, and decreased p62 and ubiquitinated protein levels. RSV did not change activities of signals that regulate autophagy including AMPK and mTORC1.[Conclusion] These results suggest that RSV attenuates age-related muscle atrophy and motor dysfunction by activating SIRT1 and promoting autophagy.