Torcinaro Alessio, Cappetta Donato, De Santa Francesca, Telesca Marialucia, Leigheb Massimiliano, Berrino Liberato, Urbanek Konrad, De Angelis Antonella, Ferraro Elisabetta
Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), Via Ercole Ramarini, 32, Monterotondo, 00015 Rome, Italy.
Istituto Dermopatico dell'Immacolata (IDI), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Experimental Immunology Laboratory, Via Monti di Creta, 104, 00167 Rome, Italy.
Metabolites. 2022 Jul 18;12(7):663. doi: 10.3390/metabo12070663.
Sarcopenia is defined as the loss of muscle mass associated with reduced strength leading to poor quality of life in elderly people. The decline of skeletal muscle performance is characterized by bioenergetic impairment and severe oxidative stress, and does not always strictly correlate with muscle mass loss. We chose to investigate the ability of the metabolic modulator Ranolazine to counteract skeletal muscle dysfunctions that occur with aging. For this purpose, we treated aged C57BL/6 mice with Ranolazine/vehicle for 14 days and collected the and muscles for histological and gene expression analyses, respectively. We found that Ranolazine treatment significantly increased the muscle strength of aged mice. At the histological level, we found an increase in centrally nucleated fibers associated with an up-regulation of genes encoding MyoD, Periostin and Osteopontin, thus suggesting a remodeling of the muscle even in the absence of physical exercise. Notably, these beneficial effects of Ranolazine were also accompanied by an up-regulation of antioxidant and mitochondrial genes as well as of NADH-dehydrogenase activity, together with a more efficient protection from oxidative damage in the skeletal muscle. These data indicate that the protection of muscle from oxidative stress by Ranolazine might represent a valuable approach to increase skeletal muscle strength in elderly populations.
肌肉减少症的定义是，老年人肌肉质量流失并伴有力量下降，导致生活质量不佳。骨骼肌功能下降的特征是生物能量受损和严重氧化应激，且并不总是与肌肉质量损失严格相关。我们选择研究代谢调节剂雷诺嗪对抗衰老过程中发生的骨骼肌功能障碍的能力。为此，我们用雷诺嗪/赋形剂处理老年C57BL/6小鼠14天，分别收集 和 肌肉用于组织学和基因表达分析。我们发现，雷诺嗪治疗显著提高了老年小鼠的肌肉力量。在组织学水平上，我们发现中央核纤维增加，同时编码MyoD、骨膜蛋白和骨桥蛋白的基因上调，这表明即使在没有体育锻炼的情况下肌肉也发生了重塑。值得注意的是，雷诺嗪的这些有益作用还伴随着抗氧化和线粒体基因的上调以及NADH脱氢酶活性的增加，同时对骨骼肌氧化损伤的保护作用更强。这些数据表明，雷诺嗪对肌肉氧化应激的保护作用可能是增加老年人群骨骼肌力量的一种有价值的方法。
