Life-span extension /methionine sulfoxide reductase

延长寿命/蛋氨酸亚砜还原酶

• 批准号: 6611894
• 负责人: TOSHINORI HOSHI
• 金额: $ 7.93万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6611894
• 关键词: Drosophilidae; antioxidants; arthropod genetics; behavior test; body physical activity; gene induction /repression; genetic manipulation; genetic models; genetically modified animals; longevity; mature animal; methionine; mifepristone; oxidative stress; oxidoreductase; paraquat; reproduction; sex behavior

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.

据推测，细胞成分的氧化损伤会加速衰老并缩短生物体的寿命。许多物种的衰老都伴随着体力活动和生殖活力的下降。人们已经提出了多种减少氧化损伤以延长寿命的策略。氨基酸蛋氨酸很容易被氧化，氧化蛋氨酸的修复是由肽蛋氨酸亚砜还原酶（MSRA）催化的。在这里，我们将研究抗氧化剂 MSRA 在模式生物果蝇中的寿命延长作用。先前的结果表明，在果蝇的整个生命周期中MSRA的组成型过度表达显着延长了寿命。 这里提出的研究将测试如果MSRA在动物成年后过度表达，是否有可能延长寿命并延缓衰老引起的体力活动水平和生殖能力的下降。使用依赖于 RU486 的“GeneSwitch”协议实现 MSRA 的时间控制过度表达。检查诱导的 MSRA 过度表达对生存分布、氧化应激抵抗、体力活动和生殖行为的影响。预期结果将深入了解 MSRA 延长寿命作用的潜在机制，并表明 MSRA 是一种可能的治疗剂，可以减缓衰老和衰老引起的生理和行为变化。