With age, somatically derived mitochondrial DNA (mtDNA) deletion mutations arise in many tissues and species. In skeletal muscle, deletion mutations clonally accumulate along the length of individual fibers. At high intrafiber abundances, these mutations disrupt individual cell respiration and are linked to the activation of apoptosis, intrafiber atrophy, breakage, and necrosis, contributing to fiber loss. This sequence of molecular and cellular events suggests a putative mechanism for the permanent loss of muscle fibers with age. To test whether mtDNA deletion mutation accumulation is a significant contributor to the fiber loss observed in aging muscle, we pharmacologically induced deletion mutation accumulation. We observed a 1200% increase in mtDNA deletion mutation‐containing electron transport chain‐deficient muscle fibers, an 18% decrease in muscle fiber number and 22% worsening of muscle mass loss. These data affirm the hypothesized role for mtDNA deletion mutation in the etiology of muscle fiber loss at old age.

中文翻译：

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潜在的线粒体 DNA 缺失突变导致老年时肌肉纤维丢失。

随着年龄的增长，许多组织和物种中都会出现体细胞来源的线粒体 DNA (mtDNA) 缺失突变。在骨骼肌中，缺失突变沿着单根纤维的长度克隆性地积累。在高纤维内丰度下，这些突变会破坏单个细胞呼吸，并与细胞凋亡、纤维内萎缩、断裂和坏死的激活有关，从而导致纤维损失。这一系列的分子和细胞事件表明了肌肉纤维随着年龄的增长而永久丧失的推定机制。为了测试 mtDNA 缺失突变积累是否是老化肌肉中观察到的纤维损失的重要贡献者，我们在药理学上诱导了缺失突变积累。我们观察到含有 mtDNA 缺失突变的电子传递链缺陷肌纤维增加了 1200%，肌纤维数量减少 18%，肌肉质量减少 22%。这些数据证实了 mtDNA 缺失突变在老年肌纤维丢失病因学中的假设作用。