Nutritional modulation of lifespan in Drosophila

描述(申请人提供)：卡路里限制(CR)，一种在不导致营养不良的情况下降低营养水平的方法，众所周知，它可以延长从酵母到啮齿动物的各种物种的寿命。因此，随意喂养可以被视为对寿命有毒性影响。事实上，人类营养过剩是与年龄相关的疾病和死亡的主要风险因素之一。我们建议描述果蝇营养过剩的影响，并通过寻找对营养过剩表现出更高的敏感性或抵抗力的突变体来寻求缓解这些影响的方法。对相关分子途径的识别应该会通过引导我们找到显示寿命变化的下游基因，为理解这一现象提供工具。对正常果蝇和突变果蝇营养过剩引起的病理和生理变化的检查将有助于揭示它们与衰老和与年龄相关的疾病的关系。大多数研究都是针对营养不良作为延长寿命的有益因素的影响。这一提议代表了另一种方法，专注于过度营养以夸大有害影响，从而提供一个敏感的系统，在其中发现改善它们的方法。

DESCRIPTION (provided by applicant): Caloric restriction (CR), a decrease in nutritional level without causing malnutrition, is well known to increase lifespan across species, from yeast to rodents. Ad libitum feeding can therefore be viewed as having a toxic effect on lifespan. Indeed, overnutrition in humans is one of the leading risk factors for age-related diseases and mortality. We propose to characterize the effects of overnutrition in Drosophila, and seek ways to mitigate them by finding mutants that show either enhanced sensitivity or resistance to overnutrition. The identification of molecular pathways involved should provide tools in the understanding of this phenomenon, by leading us to the downstream genes that manifest the lifespan changes. Examination of the pathological and physiological changes resulting from overnutrition in normal and mutant flies will cast light on their involvement in aging and age-related diseases. Most investigations have been directed at the effects of undernutrition as a beneficial factor in extending lifespan. This proposal represents an alternate approach, focusing on overnutrition to exaggerate deleterious effects, thus providing a sensitized system in which to discover methods of ameliorating them.