Nutritional modulation of lifespan in Drosophila

描述（由申请人提供）：热量限制（CR），在不引起营养不良的情况下降低营养水平，众所周知，可以延长从酵母到啮齿动物等物种的寿命。因此，随意取食可以被视为对寿命有毒害作用。事实上，人类营养过剩是与年龄有关的疾病和死亡的主要危险因素之一。我们建议描述营养过剩对果蝇的影响，并通过寻找对营养过剩表现出增强敏感性或抗性的突变体来寻求减轻它们的方法。通过引导我们找到表现寿命变化的下游基因，所涉及的分子途径的识别应该为理解这一现象提供工具。检查正常和突变果蝇的营养过剩引起的病理和生理变化将揭示它们在衰老和与年龄相关的疾病中的作用。大多数研究都把营养不良作为延长寿命的有利因素。这一建议代表了另一种方法，关注营养过剩以夸大有害影响，从而提供一个敏感的系统，在这个系统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.