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.

对细胞成分的氧化损伤被认为会加速衰老并缩短生物体的寿命。许多物种的衰老伴随着体力活动和生殖活力的下降。已经提出了各种策略来最小化氧化损伤以增加寿命。氨基酸甲硫氨酸容易氧化，氧化甲硫氨酸的修复由肽甲硫氨酸亚砜还原酶（MSRA）催化。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。以往的研究结果表明，在果蝇的整个生命周期中，组成性过表达MSRA显着延长寿命。 本文提出的研究将测试如果MSRA在动物达到成年后过表达，是否有可能延长寿命并延迟衰老诱导的体力活动水平和生殖能力下降。使用RU 486依赖性“GeneSwitch”方案实现MSRA的时间控制的过表达。研究了诱导MSRA过表达对存活分布、抗氧化应激、体力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见解，并暗示MSRA可能是一种延缓衰老和衰老诱导的生理和行为变化的治疗剂。