Life-span extension /methionine sulfoxide reductase

对细胞成分的氧化损伤被认为会加速衰老，缩短生物体的寿命。许多物种的衰老都伴随着体力活动和生殖活力的下降。人们提出了各种减少氧化损伤以延长寿命的策略。氨基酸蛋氨酸是一种易被氧化的氨基酸，被氧化的蛋氨酸的修复是由缩氨酸亚砜还原酶（methionine亚砜reductase， MSRA）催化的。在这里，我们将研究抗氧化剂MSRA在模式生物果蝇中延长寿命的作用。先前的研究结果表明，MSRA在果蝇整个生命周期中的组成性过表达显著延长了果蝇的寿命。本研究将测试在动物成年后，如果MSRA过度表达，是否有可能延长寿命并延缓衰老引起的身体活动水平和生殖能力的下降。使用ru486依赖的“GeneSwitch”协议实现暂时控制的MSRA过表达。研究了诱导的MSRA过表达对存活分布、氧化应激抵抗、身体活动和生殖行为的影响。预期的结果将为MSRA延长寿命的机制提供深入的见解，并暗示MSRA可能是减缓衰老和衰老引起的生理和行为变化的治疗药物。

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.