Resistance training in patients with single, large-scale deletions of mitochondrial DNA
Resistance training in patients with single, large-scale deletions of mitochondrial DNA
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DOI：
10.1093/brain/awn252
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发表时间：
2008-11-01
期刊：
影响因子：
14.5
通讯作者：
Taivassalo, Tanja
中科院分区：
文献类型：
--
作者：
Murphy, Julie L.;Blakely, Emma L.;Taivassalo, Tanja
线粒体异质性的显著组织变异存在于散发性线粒体DNA（mtDNA）突变的患者中。尽管在成熟骨骼肌中丰度很高，但在卫星细胞中致病突变的水平很低或检测不到。这些典型的静止有丝分裂细胞的激活和随后的野生型mtDNA模板转移到成熟肌肉已被提出作为恢复这些患者更正常的线粒体基因型和功能的一种手段。由于抗阻训练被认为是活跃骨骼肌中卫星细胞诱导的刺激因素，本研究试图通过评估以下内容来评估抗阻训练对8名单次大规模mtDNA缺失患者的治疗潜力：峰值肌肉力量和氧化能力的生理决定因素以及肌肉活检衍生的损伤测量、mtDNA突变负荷、氧化损伤水平和卫星细胞数量。我们的研究结果表明，12周的渐进式超负荷腿部阻力训练导致：（i）增加肌肉力量;（ii）肌纤维损伤和再生;（iii）增加神经细胞粘附分子（NCAM）阳性卫星细胞的比例;（iv）改善肌肉氧化能力。综上所述，我们认为这些发现支持了阻力运动诱导的线粒体基因转移的假设，在含有卫星细胞的肌肉中，这些卫星细胞具有低水平或缺失的mtDNA。进一步的研究是必要的，以完善参数的运动训练方案，以最大限度地提高线粒体基因型和治疗潜力的患者与选定的，零星突变的骨骼肌线粒体DNA的训练效果。
Dramatic tissue variation in mitochondrial heteroplasmy has been found to exist in patients with sporadic mitochondrial DNA (mtDNA) mutations. Despite high abundance in mature skeletal muscle, levels of the causative mutation are low or undetectable in satellite cells. The activation of these typically quiescent mitotic cells and subsequent shifting of wild-type mtDNA templates to mature muscle have been proposed as a means of restoring a more normal mitochondrial genotype and function in these patients. Because resistance exercise is known to serve as a stimulus for satellite cell induction within active skeletal muscle, this study sought to assess the therapeutic potential of resistance training in eight patients with single, large-scale mtDNA deletions by assessing: physiological determinants of peak muscle strength and oxidative capacity and muscle biopsy-derived measures of damage, mtDNA mutation load, level of oxidative impairment and satellite cell numbers. Our results show that 12 weeks of progressive overload leg resistance training led to: (i) increased muscle strength; (ii) myofibre damage and regeneration; (iii) increased proportion of neural cell adhesion molecule (NCAM)-positive satellite cells; (iv) improved muscle oxidative capacity. Taken together, we believe these findings support the hypothesis of resistance exercise-induced mitochondrial gene-shifting in muscle containing satellite cells which have low or absent levels of deleted mtDNA. Further investigation is warranted to refine parameters of the exercise training protocol in order to maximize the training effect on mitochondrial genotype and treatment potential for patients with selected, sporadic mutations of mtDNA in skeletal muscle.