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Oligonol Alleviates Sarcopenia by Regulation of Signaling Pathways Involved in Protein Turnover and Mitochondrial Quality
Author(s) -
Chang YunChing,
Chen YiTien,
Liu HungWen,
Chan YinChing,
Liu MingYi,
Hu ShuHui,
Tseng WeiTai,
Wu HsinLing,
Wang MingFu,
Chang SueJoan
Publication year - 2019
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201801102
Subject(s) - mfn2 , mitochondrial biogenesis , tfam , mitochondrial fusion , pink1 , skeletal muscle , mitochondrion , sarcopenia , autophagy , microbiology and biotechnology , protein degradation , nrf1 , mitochondrial fission , downregulation and upregulation , biology , medicine , mitophagy , endocrinology , protein kinase b , protein turnover , phosphorylation , mitochondrial dna , apoptosis , biochemistry , protein biosynthesis , gene
Scope Oligonol has been shown to moderate mitochondrial biogenesis, protein synthesis, and protein degradation in diabetic mice in a previous study. It is therefore hypothesized that oligonol alleviated sarcopenia by regulating pathways involved in protein turnover and mitochondrial quality. Methods and results The 32‐week‐old senescence‐accelerated mouse prone 8 (SAMP8) mice are fed with chow diet containing 200 mg kg −1 oligonol for 8 weeks. Oligonol supplementation increased skeletal muscle mass, cross‐sectional areas, and grip strength in SAMP8 mice. Oligonol increased phosphorylation of AKT/mTOR/p70sk6, inhibited nuclear localization of FoxO3a and NFκB, and decreased transcription of MuRF‐1 and MAFbx in skeletal muscle of SAMP8 mice. Downregulation of mitochondrial biogenesis genes ( PGC‐1α and Tfam ) and mitochondrial fusion genes ( Mfn2 and Opa1) , loss of PINK1, overexpression of Atg13, LC3‐II, and p62, and abundant accumulation of autophagosomes and lysosomes in skeletal muscle of SAMP8 mice are limited by oligonol. Furthermore, oligonol reduced expression of released cytochrome c and cleaved caspase‐9 in skeletal muscle of SAMP8 mice. Conclusion Regulating pathways involved in protein synthesis and degradation, mitochondrial biogenesis, mitochondrial fusion/fission, autophagy, and mitochondria‐dependent apoptosis by oligonol contribute to positive protein turnover and mitochondrial quality, thus increasing muscle mass and strength in SAMP8 mice.