| Mitochondrial alterations accumulate with age and have been suggested to lead to mitochondrial and cellular dysfunction, possibly contributing to senescence and late life diseases. Evidence in support of this theory comes from the identification of mitochondrial DNA (mtDNA) mutations which accumulate with age in human and rodent post-mitotic tissues. The total pool of mutated mtDNA genomes, however, is very low (;To gain insight into mitochondrial DNA deletion formation and to further study age-related changes in mitochondrial function, D. melanogaster was utilized as a biogerontologic model. Although multiple mitochondrial DNA deletions were identified throughout development and aging they did not increase in number or abundance. However, during this period, numerous changes in mitochondrial function and gene expression were detected. The activity of several electron transport system complexes was measured, with statistically significant declines only found for complex IV: cytochrome c oxidase (COX). The abundance of ATP also decreased steadily throughout first 45 days of adulthood. To determine what factor(s) were contributing to COX activity reductions, the abundance of cytochrome oxidase I (coxI; mitochondrial-encoded component of COX) and several other mitochondrial transcripts was measured. Mitochondrial RNA steady-state abundance declined 5-10-fold with age and was associated with life-expectancy. Histological examination of aging flies revealed preferential reductions in the highly oxidative indirect flight muscles and brain, while expression in the ventriculous remained unchanged.;Oxidative stress is inversely related to longevity in D. melanogaster. Analysis of anti-oxidant enzyme mutant or hydrogen peroxide treated flies show that oxidative stress leads to preferential reductions in mtRNA and in COX activity. These studies demonstrate that oxidative stress is closely associated with reductions in mitochondrial transcript levels and support the hypothesis that oxidative stress may contribute to mitochondrial dysfunction and aging in D. melanogaster. |
