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, critical studies testing the validity of this hypothesis have not as yet been conducted. The purpose of the proposed experiments is to determine if oxidative stress is a causal factor in governing the rate of aging in Drosophila melanogaster, using a molecular genetic approach. The effect of overexpression of antioxidant genes for superoxide dismutase, catalase and seleno-dependent glutathione peroxidase, either alone or in combination, on life span and age-related changes in Drosophila will be examined. Because the overexpression on one antioxidant gene may create a biochemical imbalance in the inter-related defense mechanisms, a major effort will be made to construct transgenic strains with balanced antioxidant defenses. Results of this study should indicate if the primary enzymatic defense against partially reduced oxygen species are a causal factor in the aging process of Drosophila.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG008459-05
Application #
3120090
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1989-07-01
Project End
1994-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Southern Methodist University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75205
Candas, M; Sohal, R S; Radyuk, S N et al. (1997) Molecular organization of the glutathione reductase gene in Drosophila melanogaster. Arch Biochem Biophys 339:323-34
Orr, W C; Orr, E C; Legan, S K et al. (1996) Molecular analysis of the Drosophila catalase gene. Arch Biochem Biophys 330:251-8
Sohal, R S; Agarwal, A; Agarwal, S et al. (1995) Simultaneous overexpression of copper- and zinc-containing superoxide dismutase and catalase retards age-related oxidative damage and increases metabolic potential in Drosophila melanogaster. J Biol Chem 270:15671-4
Orr, W C; Sohal, R S (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263:1128-30
Sohal, R S (1993) The free radical hypothesis of aging: an appraisal of the current status. Aging (Milano) 5:3-17
Orr, W C; Sohal, R S (1993) Effects of Cu-Zn superoxide dismutase overexpression of life span and resistance to oxidative stress in transgenic Drosophila melanogaster. Arch Biochem Biophys 301:34-40
Orr, W C; Arnold, L A; Sohal, R S (1992) Relationship between catalase activity, life span and some parameters associated with antioxidant defenses in Drosophila melanogaster. Mech Ageing Dev 63:287-96
Murphy, E A; Breitner, J C (1992) Threshold model in the genetics of age-dependent disease in twins: I. General principles as applied to Alzheimer disease. Am J Med Genet 42:842-50
Sohal, R S; Brunk, U T (1992) Mitochondrial production of pro-oxidants and cellular senescence. Mutat Res 275:295-304
Sohal, R S; Orr, W C (1992) Relationship between antioxidants, prooxidants, and the aging process. Ann N Y Acad Sci 663:74-84

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