Is Cell Aging Caused by Respiration-Dependent Injury to the Mitochondrial Genome?
作者:
J.E. Fleming,
J. Miquel,
S.F. Cottrell,
L.S. Yengoyan,
A.C. Economos,
期刊:
Gerontology
(Karger Available online 1982)
卷期:
Volume 28,
issue 1
页码: 44-53
ISSN:0304-324X
年代: 1982
DOI:10.1159/000212510
出版商: S. Karger AG
关键词: Mitochondrial DNA;Cell aging;Free radicals;Mitochondrial genome
数据来源: Karger
摘要:
Though intrinsic mitochondrial aging has been considered before as a possible cause of cellular senescence, the mechanisms of such mitochondrial aging have remained obscure. In this article we expand on our hypothesis of free-radical-induced inhibition of mitochondrial replenishment in fixed postmitotic cells. We maintain that the respiration-dependent production of superoxide and hydroxyl radicals may not be fully counteracted, leading to a continuous production of lipoperoxides and malonaldehyde in actively respiring mitochondria. These compounds, in turn, can easily react with the mitochondrial DNA which is in close spatial relationship with the inner mitochondrial membrane, producing an injury that the mitochondria may be unable to counteract because of their apparent lack of adequate repair mechanisms. Mitochondrial division may thus be inhibited leading to age-related reduction of mitochondrial numbers, a deficit in energy production with a concomitant decrease in protein synthesis, deterioration of physiological performance, and, therefore, of organismic performance.
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