Genetic repression of the antioxidant enzymes reduces the lifespan in Drosophila melanogaster

AbstractAging is a biological process associated with gradual loss of function caused by cellular and molecular damages ultimately leading to mortality. Free radicals are implicated in oxidative damage which affects the longevity of organisms. Natural cellular defenses involving antioxidant enzymes delay or prevent oxidative damage and, therefore, influence the aging process and longevity has been shown in many species includingDrosophila. We and others have shown that oxidative resistance is an important mechanism in the aging process inDrosophila. Therefore, we hypothesized that repressing endogenous antioxidant defenses shortens longevity inDrosophila. To study the influence of natural defense mechanisms against oxidative stress in aging, we have investigated the effect of genetic repression of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), on longevity inDrosophila using transgenic RNAi flies and in vivo inhibition of the enzymes with chemical inhibitors. RNAi lines ofDrosophila viz.,UAS-sod1-IR andUAS-cat-IR, are driven ubiquitously usingAct5C-Gal4 andTubulin-Gal4 to achieve the suppression of SOD1 and CAT activities, respectively. We show that genetic repression of SOD1 and CAT by RNAi in transgenic flies led to drastically reduced longevity (SOD1, 77%; CAT, 83%), presenting the evidence for the role of endogenous antioxidant defenses in lifespan extension inDrosophila. Further, our study shows that the enzyme inhibitors, diethyldithiocarbamate ...
Source: Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology - Category: Physiology Source Type: research