Role of mitochondrial DNA mutations in human aging: Implications for the central nervous system and muscle
Role of mitochondrial DNA mutations in human aging: Implications for the central nervous system and muscle
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DOI：
10.1002/ana.410430212
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发表时间：
1998-02-01
影响因子：
11.2
通讯作者：
Turnbull, DM
中科院分区：
文献类型：
--
作者：
Brierley, EJ;Johnson, MA;Turnbull, DM
有人提出，随着年龄增长出现神经和肌肉功能障碍的一种机制涉及线粒体。线粒体含有哺乳动物细胞中细胞核外的唯一DNA。线粒体DNA（mtDNA）具有较高的突变率，并且在老年受试者的组织中已发现低水平的致病性突变。然而，这些突变在衰老过程中的作用并不确定，除非能够确定一种会导致生化缺陷的机制。在正常老年受试者的肌肉组织中，我们发现存在细胞色素c氧化酶活性极低的肌纤维，这表明存在mtDNA缺陷。在这些细胞色素c氧化酶缺乏的纤维中，我们发现了非常高水平的突变型mtDNA。此外，不同的纤维中存在不同的mtDNA突变，这解释了为什么在老年受试者的组织中单个突变的总体发生率较低。这些研究表明，在正常人组织中生化和遗传缺陷之间存在与年龄相关的直接关联，并且mtDNA异常参与了人类肌肉的衰老过程。
It has been proposed that one mechanism for nerve and muscle dysfunction with age involves the mitochondria. Mitochondria contain the only DNA outside the nucleus in mammalian cells. Mitochondrial DNA (mtDNA) has a high mutation rate, and low levels of pathogenic mutations have been found in tissues from elderly subjects. However, the role of these mutations in the aging process is uncertain unless a mechanism can be identified that would lead to a biochemical defect. In muscle tissue from normal elderly subjects we show that there are muscle fibers with very low activity of cytochrome c oxidase, suggestive of a mtDNA defect. In these cytochrome c oxidase-deficient fibers we have found very high levels of mutant mtDNA. In addition, different mtDNA mutations are present in different fibers, which explains why there is a low overall incidence of an individual mutation in tissues from elderly subjects. These studies show a direct age-related correlation between a biochemical and genetic defect in normal human tissues and that mtDNA abnormalities are involved in the aging process in human muscle.