Mitochondrial DNA deletion mutations and sarcopenia
Mitochondrial DNA deletion mutations and sarcopenia
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DOI：
10.1111/j.1749-6632.2002.tb02111.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
McKiernan, S
中科院分区：
文献类型：
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作者：
Aiken, J;Bua, E;McKiernan, S
这篇手稿总结了我们对线粒体DNA和酶异常的研究，随着年龄的增长，在骨骼肌中积累。在这些研究中使用了特定的股四头肌，大鼠的股直肌和恒河猴的股外侧肌。这些肌肉表现出相当大的肌肉减少症，肌肉质量随着年龄的增长而减少。老年骨骼肌中mtDNA缺失突变和酶异常的局灶性积累需要组织学方法，其中每根肌肉纤维沿着其长度检查电子传递系统（ETS）酶活性。这些研究表明，ETS异常在老化肌肉纤维的小区域内积累到高水平。伴随ETS异常，我们观察到纤维内萎缩，在许多情况下，纤维断裂。激光捕获显微解剖有助于分析来自组织学切片的单个纤维，并证明mtDNA缺失突变与ETS异常之间存在密切关联。在这些结果的基础上，我们提出了骨骼肌纤维随年龄损失的分子基础，这一过程始于mtDNA缺失事件，最终以肌纤维断裂和损失告终。
This manuscript summarizes our studies on mitochondrial DNA and enzymatic abnormalities that accumulate, with age, in skeletal muscle. Specific quadricep muscles, rectus femoris in the rat and vastus lateralis in the rhesus monkey, were used in these studies. These muscles exhibit considerable sarcopenia, the loss of muscle mass with age. The focal accumulation of mtDNA deletion mutations and enzymatic abnormalities in aged skeletal muscle necessitates a histologic approach in which every muscle fiber is examined for electron transport system (ETS) enzyme activity along its length. These studies demonstrate that ETS abnormalities accumulate to high levels within small regions of aged muscle fibers. Concomitant with the ETS abnormalities, we observe intrafiber atrophy and, in many cases, fiber breakage. Laser capture microdissection facilitates analysis of individual fibers from histologic sections and demonstrates a tight association between mtDNA deletion mutations and the ETS abnormalities. On the basis of these results, we propose a molecular basis for skeletal muscle fiber loss with age, a process beginning with the mtDNA deletion event and culminating with muscle fiber breakage and loss.