Genetic Model of Caloric Restriction

描述（由申请人提供） 热量限制（CR）已经成为延长寿命的最成功的方法。 几种不同实验生物的寿命。 CR减速 不可逆转的生理衰退和与年龄相关的病理学的发生 动物们。 虽然目前还不知道CR是如何导致寿命延长的 延伸，一个合理的假设是，它通过减少氧化 损害 研究人员已经确定了Indy基因的突变， 大大延长了果蝇的寿命。 该基因是一种果蝇的同源基因， 人脱羧钠协同转运蛋白，参与转运Krebs 循环中间体 这表明安迪可能在能源领域发挥作用， 生产 Indy在脂肪体、卵母细胞和消化道中均有表达， 苍蝇中间代谢的地方。 根据预测的作用， 研究人员假设，在能量平衡的基因突变， Indy基因破坏正常的能量产生并导致果蝇的一种状况 类似于CR。 因此，他们认为延长寿命的机制 在Indy突变体中的机制与热量限制动物中的机制相似。 这使得研究人员可以使用Indy突变果蝇作为遗传模型 研究CR的延寿作用，以及CR与应力的关系 抵抗和防御机制。 本研究的目的是验证 寿命延长的机制与CR相似，并确定它是否 与抗应激能力和/或更高的防御能力的增加有关 抗活性氧化物质（ROS）。 调查人员将确定 雌性突变果蝇在正常、低热量和高热量饮食下的跨度， 与对照组的果蝇进行比较。 第二，确定关键的变化， ROS的代谢，它们将决定印第蝇对 温度、饥饿、百草枯和高氧。 最后，他们将检查 通过确定Indy突变是否可以 拯救SOD和过氧化氢酶突变果蝇的缩短寿命。 的目标 这些研究的目的是了解这些疾病的分子和遗传机制， CR延长寿命。 这些研究旨在为未来的 确定CR可降低ROS的机制的研究 生产导致对生物体的多种有益效果。

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.