Coapplication of magnesium supplementation and vibration modulate macrophage polarization to attenuate sarcopenic muscle atrophy through PI3K/Akt/mTOR signaling pathway

Can Cui, Zhengyuan Bao, Simon Kwoon-Ho Chow, Ronald Man Yeung Wong, Ailsa Welch, Ling Qin, Wing Hoi Cheung

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Abstract

Sarcopenia is an age-related geriatric syndrome characterized by the gradual loss of muscle mass and function. Low-magnitude high-frequency vibration (LMHFV) was shown to be beneficial to structural and functional outcomes of skeletal muscles, while magnesium (Mg) is a cofactor associated with better indices of skeletal muscle mass and strength. We hypothesized that LMHFV, Mg and their combinations could suppress inflammation and sarcopenic atrophy, promote myogenesis via PI3k/Akt/mTOR pathway in senescence-accelerated mouse P8 (SAMP8) mice and C2C12 myoblasts. Results showed that Mg treatment and LMHFV could significantly decrease inflammatory expression (C/EBPα and LYVE1) and modulate a CD206-positive M2 macrophage population at month four. Mg treatment also showed significant inhibitory effects on FOXO3, MuRF1 and MAFbx mRNA expression. Coapplication showed a synergistic effect on suppression of type I fiber atrophy, with significantly higher IGF-1, MyoD, MyoG mRNA (p < 0.05) and pAkt protein expression (p < 0.0001) during sarcopenia. In vitro inhibition of PI3K/Akt and mTOR abolished the enhancement effects on myotube formation and inhibited MRF mRNA and p85, Akt, pAkt and mTOR protein expressions. The present study demonstrated that the PI3K/Akt/mTOR pathway is the predominant regulatory mechanism through which LMHFV and Mg enhanced muscle regeneration and suppressed atrogene upregulation.
Original languageEnglish
Article number12944
JournalInternational Journal of Molecular Sciences
Volume23
Issue number21
Early online date26 Oct 2022
DOIs
Publication statusPublished - Nov 2022

Keywords

  • LMHFV
  • PI3K/Akt/mTOR pathway
  • atrophy
  • macrophage
  • magnesium
  • sarcopenia

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