Life-span extension /methionine sulfoxide reductase

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Oxidative damages to cellular constituents are postulated to accelerate aging and shorten the life-span of an organism. Aging in many species is accompanied by declines in physical activity and reproductive vigor. A variety of strategies to minimize oxidative damages to increase the life- span have been proposed. The amino acid methionine is easily oxidized and the repair of oxidized methionine is catalyzed by the enzyme peptide methionine sulfoxide reductase (MSRA). Here we will examine life-span extension roles of the anti-oxidant MSRA in the model organism Drosophila. Previous results suggested that constitutive over-expression of MSRA throughout the entire Drosophila life markedly extended the life-span. The study proposed here will test whether it is possible to extend the life-span and delay senescence-induced declines in the physical activity level and reproductive capacity if MSRA is over- expressed after the animal reaches adulthood. Temporally-controlled over-expression of MSRA is achieved using the RU486-dependent "GeneSwitch" protocol. The effects of induced MSRA over-expression on the survival distribution, oxidative stress resistance, physical activity and reproductive behavior are examined. The results expected will provide insights into the mechanism underlying the life-extension effect of MSRA and implicate MSRA a possible therapeutic agent to slow aging and senescence-induced changes in physiology and behavior.