Elucidation of the mechanisms of age-related muscle atrophy and development of novel therapies for sarcopenia
Description: Skeletal muscles are composed of two types of muscle fibers, and these fibers can be switched between fast and slow under several circumstances. However, it is unclear how muscle fiber type transitions are regulated. In this study, we have developed transgenic mice, which allow distinguishing each muscle fiber type by fluorescent proteins. Using cultured myotubes derived from these mice, we have identified several factors that could influence slow-to-fast or fast-to-slow fiber type transition. One of them, CCL19, C-C motif chemokine ligand 19, could induce fast-to-slow type fiber transition and reduced the basal respiration in vitro, and the phenotypes were validated in vivo. Additionally, several experiments using knockout mice have revealed that muscle fiber transition induced by CCL19 was mediated through Rgs4-Sirt1 signaling pathway. Our results were proposed the novel pathway that induced muscle fiber type transitions.
Amount: ¥4,550,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2018-04-01
End date: 2021-03-31
Investigator: Norio Motohashi
Institution: National Center of Neurology and Psychiatry(2019-2020)Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology(2018)
Funded outputs count: 8
Funder award ID: 18K11067
OpenAlex ID: G5191783052