Coapplication of Magnesium Supplementation and Vibration Modulate Macrophage Polarization to Attenuate Sarcopenic Muscle Atrophy through PI3K/Akt/mTOR Signaling Pathway

• Published in: International journal of molecular sciences Vol. 23; no. 21; p. 12944
• Main Authors: Cui, Can, Bao, Zhengyuan, Chow, Simon Kwoon-Ho, Wong, Ronald Man Yeung, Welch, Ailsa, Qin, Ling, Cheung, Wing Hoi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.10.2022; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; Aging; AKT protein; Animals; Atrophy; Body composition; Dietary Supplements; FOXO3 protein; Gene expression; Inflammation; Insulin-like growth factor I; LMHFV; macrophage; Macrophages; Macrophages - metabolism; Magnesium; Magnesium - pharmacology; Mice; Muscle strength; Muscle, Skeletal - metabolism; Muscles; Muscular Atrophy - metabolism; Musculoskeletal system; Myoblasts; MyoD protein; Myogenesis; Myotubes; Older people; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt/mTOR pathway; Proteins; Proto-Oncogene Proteins c-akt - metabolism; RNA, Messenger; Sarcopenia; Sarcopenia - pathology; Senescence; Signal Transduction; Skeletal muscle; Structure-function relationships; Synergistic effect; TOR protein; TOR Serine-Threonine Kinases - metabolism; Vibration; atrophy; macrophage; magnesium; LMHFV; PI3K/Akt/mTOR pathway; sarcopenia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232112944

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.