Mitochondrial DNA Oxidation

Mitochondrial diseases have been known for more than three decades. A refinement of the free radical theory of aging states that oxidative damage to mitochondria, particularly to mitochondrial DNA (mtDNA), is responsible for aging. About 10 years ago, oxidative damage to mtDNA was first reported, and human diseases were related to mutations of mtDNA. Subsequent reports suggested that oxidative mtDNA damage is more pronounced in old individuals and during certain diseases. Studies of animal models indicated that oxidative mtDNA damage can be ameliorated by dietary antioxidants and caloric restriction, an established method to increase life span. More recent data indicate that fragmented mtDNA is the predominant carrier of oxidized mtDNA bases and that fragments constitute a substantial amount of the total mtDNA. This article discusses the emerging relationship among mtDNA oxidation, diseases, and aging, and suggests experiments by which such a relationship can be further substantiated.