Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging.
Mitochondria do not only produce less ATP, but they also increase the production of reactive oxygen species (ROS) as by-products of aerobic metabolism in the aging tissues of the human and animals. It is now generally accepted that aging-associated respiratory function decline can result in enhanced production of ROS in mitochondria. Moreover, the activities of free radical-scavenging enzymes are altered in the aging process. The concurrent age-related changes of these two systems result in the elevation of oxidative stress in aging tissues. Within a certain concentration range, ROS may induce stress response of the cells by altering expression of respiratory genes to uphold the energy metabolism to rescue the cell. However, beyond the threshold, ROS may cause a wide spectrum of oxidative damage to various cellular components to result in cell death or elicit apoptosis by induction of mitochondrial membrane permeability transition and release of apoptogenic factors such as cytochrome c. Moreover, oxidative damage and large-scale deletion and duplication of mitochondrial DNA (mtDNA) have been found to increase with age in various tissues of the human. Mitochondria act like a biosensor of oxidative stress and they enable cell to undergo changes in aging and age-related diseases. On the other hand, it has recently been demonstrated that impairment in mitochondrial respiration and oxidative phosphorylation elicits an increase in oxidative stress and causes a host of mtDNA rearrangements and deletions. Here, we review work done in the past few years to support our view that oxidative stress and oxidative damage are a result of concurrent accumulation of mtDNA mutations and defective antioxidant enzymes in human aging.
D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species