Department of Kinesiology, McGill University, Montreal, Quebec, Canada.
Aging Cell. 2011 Dec;10(6):1047-55. doi: 10.1111/j.1474-9726.2011.00745.x.
To determine whether mitochondrial dysfunction is causally related to muscle atrophy with aging, we examined respiratory capacity, H(2) O(2) emission, and function of the mitochondrial permeability transition pore (mPTP) in permeabilized myofibers prepared from four rat muscles that span a range of fiber type and degree of age-related atrophy. Muscle atrophy with aging was greatest in fast-twitch gastrocnemius (Gas) muscle (-38%), intermediate in both the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (Sol) muscles (-21%), and non-existent in adductor longus (AL) muscle (+47%). In contrast, indices of mitochondrial dysfunction did not correspond to this differential degree of atrophy. Specifically, despite higher protein expression for oxidative phosphorylation (oxphos) system in fast Gas and EDL, state III respiratory capacity per myofiber wet weight was unchanged with aging, whereas the slow Sol showed proportional decreases in oxphos protein, citrate synthase activity, and state III respiration. Free radical leak (H(2) O(2) emission per O(2) flux) under state III respiration was higher with aging in the fast Gas, whereas state II free radical leak was higher in the slow AL. Only the fast muscles had impaired mPTP function with aging, with lower mitochondrial calcium retention capacity in EDL and shorter time to mPTP opening in Gas and EDL. Collectively, our results underscore that the age-related changes in muscle mitochondrial function depend largely upon fiber type and are unrelated to the severity of muscle atrophy, suggesting that intrinsic changes in mitochondrial function are unlikely to be causally involved in aging muscle atrophy.
为了确定线粒体功能障碍是否与衰老导致的肌肉萎缩有因果关系，我们检查了四种横跨纤维类型和衰老相关性萎缩程度范围的大鼠肌肉制备的通透肌纤维中的呼吸能力、H2O2 排放和线粒体通透性转换孔（mPTP）的功能。衰老导致的快肌比目鱼肌（Gas）肌肉萎缩最为严重（-38%），快肌伸趾长肌（EDL）和慢肌比目鱼肌（Sol）肌肉的萎缩程度中等（-21%），而内收长肌（AL）肌肉的萎缩程度不存在（+47%）。相比之下，线粒体功能障碍的指标与这种不同程度的萎缩并不对应。具体而言，尽管快肌 Gas 和 EDL 中的氧化磷酸化（oxphos）系统的蛋白表达更高，但每根肌纤维湿重的 III 状态呼吸能力在衰老过程中没有变化，而慢肌 Sol 则表现出 oxphos 蛋白、柠檬酸合酶活性和 III 状态呼吸的比例下降。III 状态呼吸下的自由基泄漏（每氧通量的 H2O2 排放）在快肌 Gas 中随着衰老而增加，而慢肌 AL 中的 II 状态自由基泄漏增加。只有快肌在衰老过程中 mPTP 功能受损，EDL 中的线粒体钙保留能力降低，Gas 和 EDL 中的 mPTP 开放时间缩短。总的来说，我们的结果强调，肌肉线粒体功能的与年龄相关变化在很大程度上取决于纤维类型，与肌肉萎缩的严重程度无关，这表明内在的线粒体功能变化不太可能是衰老肌肉萎缩的因果关系。
