Long-lived Ames dwarf mice: Oxidative damage to mitochondrial DNA in heart and brain.

Abstract

The single gene mutation of Ames dwarf mice increases their maximum longevity by around 40% but the mechanism(s) responsible for this effect remain to be identified. This animal model thus offers a unique possibility of testing the mitochondrial theory of aging. In this investigation, oxidative damage to mitochondrial DNA (mtDNA) was measured for the first time in dwarf and wild type mice of both sexes. In the brain, 8-oxo,7,8-dihydro-2'-deoxyguanosine (8-oxodG) in mtDNA was significantly lower in dwarfs than in their controls both in males (by 32%) and in females (by 36%). The heart of male dwarfs also showed significantly lower mtDNA 8-oxodG levels (30% decrease) than the heart of male wild type mice, whereas no differences were found in the heart of females. The results, taken together, indicate that the single gene mutation of Ames dwarfs lowers oxidative damage to mtDNA especially in the brain, an organ of utmost relevance for aging. Together with the previous evidence for relatively lower level of oxidative damage to mtDNA in both long-lived and caloric restricted animals, these findings suggest that lowering of oxidative damage to mtDNA is a common mechanism of life extension in these three different mammalian models.