Department of Life Sciences, National Cheng Kung University, 701, Tainan, Taiwan.
Department of Nursing, Shu-Zen College of Medicine and Management, 821, Kaohsiung, Taiwan.
Mol Nutr Food Res. 2019 May;63(10):e1801102. doi: 10.1002/mnfr.201801102. Epub 2019 Feb 28.
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.
The 32-week-old senescence-accelerated mouse prone 8 (SAMP8) mice are fed with chow diet containing 200 mg kg 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.
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.
在之前的研究中，已证实 Oligonol 可调节糖尿病小鼠中线粒体生物发生、蛋白质合成和蛋白质降解。因此，假设 Oligonol 通过调节与蛋白质周转和线粒体质量相关的途径来缓解肌肉减少症。
将 32 周龄的快速老化小鼠品系 8（SAMP8）小鼠喂食含有 200mg/kg Oligonol 的标准饮食 8 周。Oligonol 补充剂增加了 SAMP8 小鼠的骨骼肌质量、横截面积和握力。Oligonol 增加了 AKT/mTOR/p70sk6 的磷酸化，抑制了 FoxO3a 和 NFκB 的核定位，并降低了 SAMP8 小鼠骨骼肌中 MuRF-1 和 MAFbx 的转录。下调线粒体生物发生基因（PGC-1α 和 Tfam）和线粒体融合基因（Mfn2 和 Opa1）、PINK1 的缺失、Atg13、LC3-II 和 p62 的过度表达，以及自噬体和溶酶体在 SAMP8 小鼠骨骼肌中的大量积累，都受到 Oligonol 的限制。此外，Oligonol 减少了 SAMP8 小鼠骨骼肌中释放的细胞色素 c 和裂解的 caspase-9 的表达。
Oligonol 通过调节蛋白质合成和降解、线粒体生物发生、线粒体融合/分裂、自噬和线粒体依赖性凋亡的途径，有助于正向的蛋白质周转和线粒体质量，从而增加 SAMP8 小鼠的肌肉质量和力量。
