The eventual goal of this research is to understand the underlying causes of the aging process in animals. Endogenously-generated reactive oxygen species (ROS) have been widely postulated to play a causal role in the aging process. However, few studies have been conducted to directly test the validity of this hypothesis. the objective of the studies proposed here is to directly test an essential aspect of this hypothesis by examining the role of mitochondria in the aging process, using Drosophila melanogaster as a model system. Mitochondria are the main intracellular producers of superoxide anion radical (O2) and H2O2, which are the progenitors of various other ROS. During the aging process, the rate of mitochondrial )2, and H2O2 generation goes up and oxidative phosphorylation declines. The proposed study will test the hypothesis that 'an increase in the intramitochondrial activities of Mn superoxide desmutase (SOD) and catalase, which remove O2 and H2O2, respectively, would reduce the level of ROS generation by mitochondria and postpone the senescent changes in mitochondria as well as the organism'. Effect of increased intramitochondrial activities of Mn SOD and catalase on mitochondrial and organismic senescence will be studied. Whether the transgenic flies exhibit a slowing of the overall aging process will be determined on the basis of mortality data and physiological tests of fitness. Results of this study should critically test one of the central assumptions of the oxidative stress hypothesis of aging, namely that mitochondria are the main source of oxidants in cells and that oxidative stress is a major causal factor in mitochondrial and organismic senescence. This study should provide new knowledge about transgenic strategies to lower the level of oxidative stress, which can then be adapted to mammalian systems.
Showing the most recent 10 out of 68 publications
