BIO101 stimulates myoblast differentiation and improves muscle function in adult and old mice.

Autor: Serova M; Biophytis, Sorbonne Université, Paris, France., Didry-Barca B; Biophytis, Sorbonne Université, Paris, France., Deloux R; Biophytis, Sorbonne Université, Paris, France., Foucault AS; Biophytis, Sorbonne Université, Paris, France., Veillet S; Biophytis, Sorbonne Université, Paris, France., Lafont R; Biophytis, Sorbonne Université, Paris, France., Dilda PJ; Biophytis, Sorbonne Université, Paris, France., Latil M; Biophytis, Sorbonne Université, Paris, France.
Jazyk: angličtina
Zdroj: Journal of cachexia, sarcopenia and muscle [J Cachexia Sarcopenia Muscle] 2024 Feb; Vol. 15 (1), pp. 55-66. Date of Electronic Publication: 2023 Dec 08.
DOI: 10.1002/jcsm.13326
Abstrakt: Background: Muscle aging is associated with a consistent decrease in the ability of muscle tissue to regenerate following intrinsic muscle degradation, injury or overuse. Age-related imbalance of protein synthesis and degradation, mainly regulated by AKT/mTOR pathway, leads to progressive loss of muscle mass. Maintenance of anabolic and regenerative capacities of skeletal muscles may be regarded as a therapeutic option for sarcopenia and other muscle wasting diseases. Our previous studies have demonstrated that BIO101, a pharmaceutical grade 20-hydroxyecdysone, increases protein synthesis through the activation of MAS receptor involved in the protective arm of renin-angiotensin-aldosterone system. The purpose of the present study was to assess the anabolic and pro-differentiating properties of BIO101 on C2C12 muscle cells in vitro and to investigate its effects on adult and old mice models in vivo.
Methods: The effects of BIO101 on C2C12 differentiation were assessed using myogenic transcription factors and protein expression of major kinases of AKT/mTOR pathway by Western blot. The in vivo effects of BIO101 have been investigated in BIO101 orally-treated (50 mg/kg/day) adult mice (3 months) for 28 days. To demonstrate potential beneficial effect of BIO101 treatment in a sarcopenic mouse model, we use orally treated 22-month-old C57Bl6/J mice, for 14 weeks with vehicle or BIO101. Mice body and muscle weight were recorded. Physical performances were assessed using running capacity and muscle contractility tests.
Results: Anabolic properties of BIO101 were confirmed by the rapid activation of AKT/mTOR, leading to an increase of C2C12 myotubes diameters (+26%, P < 0.001). Pro-differentiating effects of BIO101 on C2C12 myoblasts were revealed by increased expression of muscle-specific differentiation transcription factors (MyoD, myogenin), resulting in increased fusion index and number of nuclei per myotube (+39% and +53%, respectively, at day 6). These effects of BIO101 were like those of angiotensin (1-7) and were abolished with the use of A779, a MAS receptor specific antagonist. Chronic BIO101 oral treatment induced AKT/mTOR activation and anabolic effects accompanied with improved physical performances in adult and old animals (maximal running distance and maximal running velocity).
Conclusions: Our data suggest beneficial anabolic and pro-differentiating effects of BIO101 rendering BIO101 a potent drug candidate for treating sarcopenia and possibly other muscle wasting disorders.
(© 2023 Biophytis. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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