Oxidative stress is associated with tissue dysfunctions that can lead to reduced health. Prior work has shown that oxidative stress contributes to both muscle atrophy and cellular senescence, which is a hallmark of aging that may drive in muscle atrophy and muscle contractile dysfunction. The purpose of the study was to test the hypothesis that cellular senescence contributes to muscle atrophy or weakness. To increase potential senescence in skeletal muscle, we used a model of oxidative stress-induced muscle frailty, the CuZn superoxide dismutase knockout (Sod1KO) mouse. We treated 6-month-old wildtype (WT) and Sod1KO mice with either vehicle or a senolytic treatment of combined dasatinib (5 mg/kg) + quercetin (50 mg/kg) (D + Q) for 3 consecutive days every 15 days. We continued treatment for 7 months and sacrificed the mice at 13 months of age. Treatment with D + Q did not preserve muscle mass, reduce NMJ fragmentation, or alter muscle protein synthesis in Sod1KO mice when compared to the vehicle-treated group. However, we observed an improvement in muscle-specific force generation in Sod1KO mice treated with D + Q when compared to Sod1KO-vehicle mice. Overall, these data suggest that reducing cellular senescence via D + Q is not sufficient to mitigate loss of muscle mass in a mouse model of oxidative stress-induced muscle frailty but may mitigate some aspects of oxidative stress-induced muscle dysfunction.

氧化应激与组织功能障碍有关，从而导致健康状况下降。先前的研究表明，氧化应激会导致肌肉萎缩和细胞衰老，这是衰老的标志，可能会导致肌肉萎缩和肌肉收缩功能障碍。该研究的目的是检验细胞衰老导致肌肉萎缩或无力的假设。为了增加骨骼肌的潜在衰老，我们使用了氧化应激诱导的肌肉衰弱模型，即 CuZn 超氧化物歧化酶敲除 ( Sod1 KO) 小鼠。我们用载体或达沙替尼 (5 mg/kg) + 槲皮素 (50 mg/kg) (D + Q) 联合治疗的6 个月大野生型 (WT) 和Sod1 KO 小鼠每 15 连续 3 天进行治疗天。我们继续治疗 7 个月，并在 13 个月大时处死小鼠。与载体治疗组相比，D + Q 治疗没有保留Sod1 KO 小鼠的肌肉质量、减少 NMJ 碎片或改变肌肉蛋白合成。然而，我们观察到，与Sod1 KO 载体小鼠相比，用 D + Q 治疗的Sod1 KO 小鼠的肌肉特异性力产生有所改善。总体而言，这些数据表明，通过 D + Q 减少细胞衰老不足以减轻氧化应激诱导的肌肉虚弱小鼠模型中的肌肉质量损失，但可能会减轻氧化应激诱导的肌肉功能障碍的某些方面。