The role of mitochondrial oxidative stress in aging.
Mitochondria are both a major source of oxidants and a target for their damaging effects, and, therefore, mitochondrial oxidative stress appears to be a cause, rather than a consequence, of cell aging. Oxidative damage in aging is particularly high in specific molecular targets, such as mitochondrial DNA and aconitase, and mitochondrial oxidative stress may drive tissue aging through intrinsic apoptosis. Mitochondrial function and morphology are impaired upon aging, as judged by a decline in membrane potential as well as by an increase in peroxide production and size of the organelles. In view of the age-related decreases in mitochondrial protein synthesis, mitochondrial transcripts, and expression of genes involved in mitochondrial turnover, the rate of this turnover might determine its susceptibility of mitochondria to oxidative damage and mutation, thus controlling the rate of cell aging. In fact, aging is a feature of differentiated somatic cells, especially postmitotic cells such as neurons or muscle cells. The age-associated mitochondrial DNA deletions focally accumulate in brain and skeletal muscle, thus contributing significantly to aging of these postmitotic tissues. Expansion of mitochondrial DNA mutations may occur through mitochondrial complementation. The use of mutants of the mitochondrial electron transport system, as well as knockouts or transgenics of mitochondrial antioxidants or repair enzymes, may provide clear-cut evidence of the precise mitochondrial mechanisms that control the rate of cell aging.
Sastre
Juan
J
Department of Physiology, University of Valencia, Avenida Blasco Ibañez 17, 46010 Valencia, Spain.
Pallardó
Federico V
FV
Viña
José
J
D000375:Aging / Q000502:physiology; D000818:Animals; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D005978:Glutathione; D010100:Oxygen