Role of mitochondrial DNA mutations in human aging: Implications for the central nervous system and muscle

被引:228
|
作者
Brierley, EJ
Johnson, MA
Lightowlers, RN
James, OFW
Turnbull, DM [1 ]
机构
[1] Univ Newcastle Upon Tyne, Sch Med, Dept Neurol, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[2] Univ Newcastle Upon Tyne, Sch Med, Dept Geriatr Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
基金
英国惠康基金;
关键词
D O I
10.1002/ana.410430212
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
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页码:217 / 223
页数:7
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