Cultured senescent myoblasts derived from human vastus lateralis exhibit normal mitochondrial ATP synthesis capacities with correlating concomitant ROS production while whole cell ATP production is decreased
Cultured senescent myoblasts derived from human vastus lateralis exhibit normal mitochondrial ATP synthesis capacities with correlating concomitant ROS production while whole cell ATP production is decreased
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DOI：
10.1007/s10522-012-9372-9
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发表时间：
2012-06-01
期刊：
影响因子：
4.5
通讯作者：
Gaster, Michael
中科院分区：
文献类型：
--
作者：
Minet, Ariane D.;Gaster, Michael
衰老的自由基理论认为，增加的氧化应激和线粒体功能障碍与衰老有关。在本研究中，我们研究了细胞衰老对肌肉能量的影响，通过比较培养的肌肉卫星细胞在早期和晚期传代次数的线粒体含量和功能。我们发现，培养的肌肉卫星细胞经历衰老表达减少线粒体质量，降低全细胞ATP水平，正常增加线粒体ATP生产下ATP利用，增加线粒体膜电位和增加超氧化物/线粒体质量和过氧化氢/线粒体质量比。此外，增加的ROS产生与相应的线粒体ATP产生相关。因此，从经历衰老的人成肌细胞分化的肌管具有减少的线粒体含量，但存在的线粒体表达正常至增加的功能能力。目前的数据表明，衰老的起源在于线粒体之外，细胞中的功能障碍可能是在单个线粒体中响应于线粒体质量降低和线粒体外能量供应减少而增加线粒体ATP合成和伴随的ROS产生之前和开始的。这可能导致线粒体的DNA，脂质和蛋白质的损伤增加，如衰老的自由基理论所假设的那样。
The free radical theory of aging says that increased oxidative stress and mitochondrial dysfunction are associated with old age. In the present study we have investigated the effects of cellular senescence on muscle energetic by comparing mitochondrial content and function in cultured muscle satellite cells at early and late passage numbers. We show that cultured muscle satellite cells undergoing senescence express a reduced mitochondrial mass, decreased whole cell ATP level, normal to increased mitochondrial ATP production under ATP utilization, increased mitochondrial membrane potential and increased superoxide/mitochondrial mass and hydrogen peroxide/mitochondrial mass ratios. Moreover, the increased ROS production correlates with the corresponding mitochondrial ATP production. Thus, myotubes differentiated from human myoblasts undergoing senescence have a reduced mitochondrial content, but the existent mitochondria express normal to increased functional capabilities. The present data suggest that the origin of aging lies outside the mitochondria and that a malfunction in the cell might be preceding and initiating the increase of mitochondrial ATP synthesis and concomitant ROS production in the single mitochondrion in response to decreased mitochondrial mass and reduced extra-mitochondrial energy supply. This then can lead to the increased damage of DNA, lipids and proteins of the mitochondria as postulated by the free radical theory of aging.