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Branched-chain amino acids (BCAAs) are essential for muscle protein synthesis and are widely acknowledged for mitigating sarcopenia. Oligonol ® (Olg), a low-molecular-weight polyphenol from Litchi chinensis , has also been found to attenuate sarcopenia by improving mitochondrial quality and positive protein turnover. This study aims to investigate the effect of Olg on BCAA-stimulated protein synthesis in sarcopenia. In sarcopenic C57BL/6 mice and senescence-accelerated mouse-prone 8 (SAMP8) mice, BCAAs were significantly decreased in skeletal muscle but increased in blood serum. Furthermore, the expressions of membrane L-type amino acid transporter 1 (LAT1) and branched-chain amino acid transaminase 2 (BCAT2) in skeletal muscle were lower in aged mice than in young mice. The administration of Olg for 8 weeks significantly increased the expressions of membrane LAT1 and BCAT2 in the skeletal muscle when compared with non-treated SAMP8 mice. We further found that BCAA deprivation via LAT1-siRNA in C2C12 myotubes inhibited the signaling of protein synthesis and facilitated ubiquitination degradation of BCAT2. In C2C12 cells mimicking sarcopenia, Olg combined with BCAA supplementation enhanced mTOR/p70S6K activity more than BCAA alone. However, blocked LAT1 by JPH203 reversed the synergistic effect of the combination of Olg and BCAAs. Taken together, changes in LAT1 and BCAT2 during aging profoundly alter BCAA availability and nutrient signaling in aged mice. Olg increases BCAA-stimulated protein synthesis via modulating BCAA transportation and BCAA catabolism. Combining Olg and BCAAs may be a useful nutritional strategy for alleviating sarcopenia.

Skeletal muscle function deficits result in metabolic disease development and physical dysfunction in older adults. Sarcopenia is characterized by a decrease in muscle mass and strength with advancing age, and it increases the risks of mobility impairments, disease development, and mortality. Lifestyle interventions involving a combination of diet and exercise to prevent and attenuate sarcopenia warrant substantial research attention. Resistance exercise training under supervision is a safe and the most effective approach to reducing age-related muscle loss and improving multiple aspects of overall health in the older population. The beneficial effects of resistance exercise training on skeletal muscle mass may be augmented by specific dietary supplements (i.e., green tea-derived natural products). The purpose of this mini review is to provide an up-to-date, evidence-based account of the effectiveness of green tea-derived natural products for supporting resistance training-induced adaptations to prevent or attenuate age-related muscle mass loss. Based on animal and clinical studies, we provide insights into supplementation with green tea-derived natural products, which may assist in the growth or maintenance of skeletal muscle and subsequently delay the onset of age-related metabolic diseases in older adults.

The senescence-accelerated mouse (SAM) prone 8 (SAMP8) has been demonstrated for muscular aging research including sarcopenia, but its underlying mechanisms remain scarce. Physiological indices and histology of skeletal muscle were analyzed in SAMP8 mice at different ages. SAMP8 mice exhibited typical features of sarcopenia at 40 weeks of age and were more time-efficient than that at 88 weeks of age in bothSAM resistant 1 (SAMR1) and C57BL/6 mice. Increase in FoxO3a-mediated transcription of Atrogin-1 and MuRF1 and decrease in phosphorylated mTOR/P70 s6k were observed at week 40 in SAMP8 mice. High oxidative stress was observed from week 24 and persisted to week 40 in SAMP8 mice evidenced by overexpression of protein carbonyl groups and reduced activities of CAT, SOD, and GPx. Downregulation of genes involved in mitochondrial biogenesis (PGC-1α, Nrf-1, Tfam, Ndufs8, and Cox5b) and in mitochondrial dynamics fission (Mfn2 and Opa1) from week 24 indicated dysregulation of mitochondrial quality control in SAMP8 mice. Impaired autophagic flux was observed in SAMP8 mice evidenced by elevated Atg13 and LC3-II accompanied with the accumulation of P62 and LAMP1. Increases in inflammatory factors (IL-6 and MCP-1), adipokines (leptin and resistin), and myostatin in serum at week 32 and decline in Pax7+ satellite cell resided next to muscle fibers at week 24 implied that muscle microenvironment contributed to the progression of sarcopenia in SAMP8 mice. Our data suggest that early alterations of mitochondrial quality control and autophagic flux worsen muscle microenvironment prior to the onset of sarcopenia.

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., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Stimulation of the ubiquitin-proteasome pathway-especially E3 ubiquitin ligases Atrogin-1 and MuRF1-is associated with muscle loss in diabetes. Elevated lipid metabolites impair myogenesis. Oligonol, a low molecular weight polyphenol derived from lychee, exhibited anti-diabetic and anti-obesity properties, suggesting it could be a proper supplement for attenuating muscle loss. Dietary (10 weeks) oligonol supplementation (20 or 200 mg/kg diet) on the skeletal muscle loss was investigated in diabetic db/db mice. Transcription factors NF-κB and FoxO3a involved in regulation of Atrogin-1 and MuRF1 were also investigated. Attenuation of muscle loss by oligonol (both doses) was associated with down-regulation of Atrogin-1 and MuRF1 gene expression. Oligonol supplementation decreased NF-κB expression in the nuclear fraction compared with db/db mice without oligonol supplement. Upregulation of sirtuin1 (SIRT1) expression prevented FoxO3a nuclear localization in db/db mice supplemented with oligonol. Marked increases in AMPKα activity and Ppara mRNA expression leading to lower lipid accumulation by oligonol provided additional benefits for attenuating muscle loss. Oligonol limited palmitate-induced senescent phenotype and cell cycle arrest and suppressed Atrogin-1 and MuRF1 mRNA expression in palmitate-treated C2C12 muscle cells, thus contributing to improving the impaired myotube formation. In conclusion, oligonol-mediated downregulation of Atrogin-1 and MuRF1 gene expression alleviates muscle loss and improves the impaired myotube formation, indicating that oligonol supplementation may be useful for the attenuation of myotube loss., Competing Interests: The authors declare no conflict of interest.