Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy
Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy
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DOI：
10.1016/j.freeradbiomed.2006.01.036
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发表时间：
2006-06-01
影响因子：
7.4
通讯作者：
Van Remmen, Holly
中科院分区：
文献类型：
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作者：
Muller, Florian L.;Song, Wook;Van Remmen, Holly
我们描述了一种新的表型在小鼠缺乏主要的抗氧化酶，铜锌-超氧化物歧化酶（SOD 1（-/-）小鼠），即一个显着的加速与年龄相关的骨骼肌质量损失。Sod 1（-/-）小鼠比野生型小鼠小17 - 20%，并且早在3 - 4个月大时就具有显著较低的肌肉质量。Sod 1（-/-）小鼠的肌肉质量随着年龄的增长而进一步减少，到20个月时，Sod 1（-/-）小鼠的后肢肌肉质量比年龄匹配的野生型小鼠低近50%。与来自年轻野生型小鼠的肌肉相比，来自年轻Sod 1（-/-）小鼠的骨骼肌组织对蛋白质、脂质和DNA的氧化损伤升高。肌肉质量的减少和氧化损伤的增加伴随着6个月龄时自愿轮跑减少40%和13个月龄时旋转杆测试性能下降，但与整体自发活动的下降无关。在一些老年Sod 1（-/-）小鼠中，肌肉质量的损失也与震颤和步态障碍的存在有关。因此，CuZnSOD的情况下施加升高的氧化应激，肌肉质量的损失，和生理后果，类似于正常的年龄相关的肌肉减少症的加速。(c)2006年爱思唯尔公司All rights reserved.
We describe a novel phenotype in mice lacking the major antioxidant enzyme, CuZn-superoxide dismutase (Sod1(-/-) mice), namely a dramatic acceleration of age-related loss of skeletal muscle mass. Sod1(-/-) mice are 17 to 20% smaller and have a significantly lower muscle mass than wildtype mice as early as 3 to 4 months of age. Muscle mass in the Sod1(-/-) mice is further reduced with age and by 20 months, the hind-limb muscle mass in Sod1(-/-) mice is nearly 50% lower than in age-matched wild-type mice. Skeletal muscle tissue from young Sod1(-/-) mice has elevated oxidative damage to proteins, lipids, and DNA compared to muscle from young wild-type mice. The reduction in muscle mass and elevated oxidative damage are accompanied by a 40% decrease in voluntary wheel running by 6 months of age and decreased performance on the Rota-rod test at 13 months of age, but are not associated with a decline in overall spontaneous activity. In some of the old Sod1(-/-) mice, the loss in muscle mass is also associated with the presence of tremors and gait disturbances. Thus, the absence of CuZnSOD imposes elevated oxidative stress, loss of muscle mass, and physiological consequences that resemble an acceleration of normal age-related sarcopenia. (c) 2006 Elsevier Inc. All rights reserved.