Age-related Differences in Dystrophin: Impact on Force Transfer Proteins, Membrane Integrity, and Neuromuscular Junction Stability
Age-related Differences in Dystrophin: Impact on Force Transfer Proteins, Membrane Integrity, and Neuromuscular Junction Stability
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DOI：
10.1093/gerona/glw109
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发表时间：
2017-05-01
影响因子：
5.1
通讯作者：
Baar, Keith
中科院分区：
文献类型：
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作者：
Hughes, David C.;Marcotte, George R.;Baar, Keith
从肌肉质量和神经肌肉接头（NMJ）稳定性下降的角度研究了肌肉力量随年龄的损失。第三个潜在因素是力量传递。本研究的目的是确定老化肌肉内力传递装置的变化以及对膜完整性和NMJ稳定性的影响。我们测量了与年龄相关的肌营养不良蛋白的损失，这是最大的屈肌。尽管抗肌萎缩蛋白mRNA增加了两倍，但仍发生了抗肌萎缩蛋白蛋白的损失。重要的是，这种差异可以通过dystromir miR-31的四到五倍上调来解释。为了补偿肌营养不良蛋白的损失，老化的肌肉含有增加的α-肌聚糖、突触营养蛋白、肌节蛋白、层粘连蛋白、β 1-整联蛋白、桥连蛋白和Z线蛋白α-辅肌动蛋白和桥连蛋白。尽管其他力传递蛋白的适应性增加，但在延长收缩后的48小时内，老年肌肉显示出更多的膜完整性受损迹象（免疫球蛋白G阳性纤维增加4倍，dysferlin mRNA增加70%）和NMJ不稳定性（Runx1，AchRd和肌细胞生成素mRNA增加14至96倍）。总的来说，这些数据表明，肌营养不良蛋白的年龄依赖性改变使肌肉膜和NMJ更容易受到收缩诱导的损伤，甚至在肌肉质量变化明显之前。
The loss of muscle strength with age has been studied from the perspective of a decline in muscle mass and neuromuscular junction (NMJ) stability. A third potential factor is force transmission. The purpose of this study was to determine the changes in the force transfer apparatus within aging muscle and the impact on membrane integrity and NMJ stability. We measured an age-related loss of dystrophin protein that was greatest in the flexor muscles. The loss of dystrophin protein occurred despite a twofold increase in dystrophin mRNA. Importantly, this disparity could be explained by the four-to fivefold upregulation of the dystromir miR-31. To compensate for the loss of dystrophin protein, aged muscle contained increased alpha-sarcoglycan, syntrophin, sarcospan, laminin, beta 1-integrin, desmuslin, and the Z-line proteins alpha-actinin and desmin. In spite of the adaptive increase in other force transfer proteins, over the 48 hours following lengthening contractions, the old muscles showed more signs of impaired membrane integrity (fourfold increase in immunoglobulin G-positive fibers and 70% greater dysferlin mRNA) and NMJ instability (14- to 96-fold increases in Runx1, AchRd, and myogenin mRNA). Overall, these data suggest that age-dependent alterations in dystrophin leave the muscle membrane and NMJ more susceptible to contraction-induced damage even before changes in muscle mass are obvious.