The general goal of the prospective studies is to understand the causes of the aging process in animals. Endogenously-generated oxygen free radicals 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 purpose of the proposed experiments is to directly test the main prediction of this hypothesis: that a decrease in the level of oxidative stress should slow down the aging process. Extra copies of genes that play key roles in the antioxidative system will be introduced into the Drosophila melanogaster genome and the impact of overexpression on age-related biochemical and physiological changes will be assessed. Effects of the overexpression of the Mn superoxide dismutase, glutathione reductase, glutamylcysteine synthetase and glucose-6-phosphate dehydrogenase will be studied; we have previously examined the effects of Cu-Zn superoxide dismutase and catalase. Because the overexpression of single antioxidative genes may create a biochemical imbalance in an inter- related defense mechanism, a major effort will be made to construct transgenic strains with balanced antioxidative defenses. Results of this study should critically test the veracity of the free radical hypothesis of aging by indicating if the major defenses against reactive oxygen species play a causal role in the aging process of Drosophila. Knowledge gained from this study should help in developing strategies for the manipulation of the aging process in mammalian systems.
Showing the most recent 10 out of 14 publications
