Genetic Model of Caloric Restriction

描述(由申请人提供) 卡路里限制(CR)已成为最成功的延长 在几个不同的实验生物体中的寿命。CR速度变慢 不可逆转的生理性衰退与年龄相关性病理的发生 动物的生命。虽然目前还不知道CR是如何导致寿命的 推而广之，一个看似合理的假设是，它通过减少氧化作用而起作用 损坏。研究人员已经确定了印地基因的突变 显著延长果蝇的寿命。该基因是一种苍蝇的同源基因 人脱羧酸钠共转运体参与Krebs的转运 循环中间体。这表明安迪可能在能源领域扮演一个角色。 制作。Indy在脂肪体、卵母细胞和消化道均有表达 苍蝇的中间代谢部位。根据预测的角色 能量平衡中的基因，研究人员假设 Indy基因扰乱了正常的能量生产，并导致果蝇的一种情况 类似于CR。因此，他们认为延长生命的机制 在印地突变体中的作用机制类似于卡路里限制动物的机制。 这使得研究人员可以使用印地突变果蝇作为遗传模型 研究CR延长寿命，以及CR与应激的关系 抵抗和防御机制。本研究的目的是验证 延长寿命的机制类似于CR，并确定它是否 与压力抵抗力的增强和/或更高的防御力有关 对抗活性氧化物种(ROS)。调查人员将确定 在正常、低卡路里和高卡路里饮食下的雌性突变果蝇的持续时间 把它们比作控制苍蝇。第二，找出关键的变化 ROS的代谢，它们将决定印地苍蝇对 温度、饥饿、百草枯和高氧血症。最后，他们将检查 通过确定Indy突变是否可以防御Indy Fly中的ROS 挽救超氧化物歧化酶和过氧化氢酶突变果蝇的寿命缩短。的目标是 这些研究是为了了解潜在的分子和遗传机制 使用寿命延长中的CR。这些研究旨在为未来铺平道路。 确定CR可降低ROS的机制的调查 生产对生物体有多种有益的影响。

DESCRIPTION (provided by applicant) Caloric restriction (CR) has emerged as the most successful way to extend the lifespan in several different experimental organisms. CR slows down irreversible physiological decline and occurrence of the age-related pathology of the animals. Although it is not yet known how CR leads to lifespan extension, a plausible hypothesis is that it acts by reducing oxidative damage. The investigators have identified mutations in the Indy gene that dramatically extend lifespan in fruit flies. The gene, a fly homologue of a human sodium decarboxylate co-transporter, is involved in transporting Krebs cycle intermediates. This suggests a possible role for Andy in energy production. Indy is expressed in fat body, oenocytes and digestive tract, all places of intermediary metabolism in flies. Based on the predicted role of the gene in energy balance, the investigators postulate that mutations in the Indy gene disrupt normal energy production and result in a condition in flies similar to CR. Therefore, they suggest that the mechanism of life extension in Indy mutants is similar to the mechanism in calorically-restricted animals. This allows the investigators to use the Indy mutant flies as a genetic model to study life extension by CR, as well the relationship between CR, stress resistance and defense mechanisms. The purpose of this study is to validate that the mechanism of life extension is similar to CR, and to determine if it is associated with an increase in stress resistance and/or higher defense against reactive oxidative species (ROS). The investigators will determine the span of lady mutant flies on normal-, low- and high-caloric diet and compare them to control flies. Second, to identify crucial changes in the metabolism of ROS, they will determine the resistance of Indy flies to temperature, starvation, paraquat and hyperoxia. Finally, they will examine the defense against ROS in Indy flies by determining if the Indy mutation can rescue the shortened lifespan of SOD and catalase mutant flies. The goal of these studies is to understand the molecular and genetic mechanisms underlying CR in lifespan extension. These studies aim to set the stage for future investigations to define the mechanisms by which CR may decrease ROS production leading to multiple beneficial effects for the organism.