Metformin delays satellite cell activation and maintains quiescence

Theodora Pavlidou, Milica Marinkovic, Marco Rosina, Claudia Fuoco, Simone Vumbaca, Cesare Gargioli, Luisa Castagnoli, Gianni Cesareni

Research output: Contribution to journalArticle

Abstract

The regeneration of the muscle tissue relies on the capacity of the satellite stem cell (SC) population to exit quiescence, divide asymmetrically, proliferate, and differentiate. In age-related muscle atrophy (sarcopenia) and several dystrophies, regeneration cannot compensate for the loss of muscle tissue. These disorders are associated with the depletion of the satellite cell pool or with the loss of satellite cell functionality. Recently, the establishment and maintenance of quiescence in satellite cells have been linked to their metabolic state. In this work, we aimed to modulate metabolism in order to preserve the satellite cell pool. We made use of metformin, a calorie restriction mimicking drug, to ask whether metformin has an effect on quiescence, proliferation, and differentiation of satellite cells. We report that satellite cells, when treated with metformin in vitro, ex vivo, or in vivo, delay activation, Pax7 downregulation, and terminal myogenic differentiation. We correlate the metformin-induced delay in satellite cell activation with the inhibition of the ribosome protein RPS6, one of the downstream effectors of the mTOR pathway. Moreover, in vivo administration of metformin induces a belated regeneration of cardiotoxin- (CTX-) damaged skeletal muscle. Interestingly, satellite cells treated with metformin immediately after isolation are smaller in size and exhibit reduced pyronin Y levels, which suggests that metformin-treated satellite cells are transcriptionally less active. Thus, our study suggests that metformin delays satellite cell activation and differentiation by favoring a quiescent, low metabolic state.

Original languageEnglish
Article number5980465
JournalStem Cells International
Volume2019
DOIs
Publication statusPublished - Jan 1 2019

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Pavlidou, T., Marinkovic, M., Rosina, M., Fuoco, C., Vumbaca, S., Gargioli, C., Castagnoli, L., & Cesareni, G. (2019). Metformin delays satellite cell activation and maintains quiescence. Stem Cells International, 2019, [5980465]. https://doi.org/10.1155/2019/5980465