Nutritional modulation of lifespan in Drosophila

果蝇寿命的营养调节

• 批准号: 7190695
• 负责人: SEYMOUR BENZER
• 金额: $ 4.86万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7190695
• 关键词: Drosophilidae; autophagy; bioenergetics; biological models; caloric dietary content; cell component structure /function; developmental genetics; dietary restriction; gene environment interaction; gene expression; genetic regulation; geriatrics; hormone regulation /control mechanism; insulin; longevity; mitochondria; nutrient intake activity; nutrition of aging; nutrition related tag; overeating; protein structure function; transcription factor

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.

描述（由申请人提供）：众所周知，热量限制（CR）是指在不引起营养不良的情况下降低营养水平，可以延长从酵母到啮齿动物等物种的寿命。因此，随意喂养可以被视为对寿命有毒性作用。事实上，人类营养过剩是与年龄相关的疾病和死亡的主要危险因素之一。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增强的敏感性或抵抗力的突变体来寻求减轻这些影响的方法。所涉及的分子途径的识别应该为理解这种现象提供工具，引导我们找到表现寿命变化的下游基因。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阐明它们与衰老和年龄相关疾病的关系。大多数研究都针对营养不良作为延长寿命的有益因素的影响。该提案代表了另一种方法，重点关注营养过剩以夸大有害影响，从而提供一个敏感系统来发现改善营养过剩的方法。