Molecular Genetics of Caloric Restriction in Aging Flies

衰老果蝇热量限制的分子遗传学

• 批准号: 6853563
• 负责人: BLANKA ROGINA
• 金额: $ 33.73万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6853563
• 关键词: Drosophilidae; aging; arthropod genetics; caloric dietary content; dietary restriction; gene mutation; genetic transcription; glucose metabolism; lipid metabolism; longevity; messenger RNA; microarray technology; molecular genetics; northern blottings; nutrition related tag; polymerase chain reaction

DESCRIPTION (provided by applicant): The goal of this proposal is to determine the molecular genetic, biochemical and physiological changes associated with two related life-extending interventions, caloric restriction and the long-lived Indy mutation. Caloric restriction (CR) is the most successful way to increase life span and delay the onset of age-related symptoms in animals. CR slows down the physiological decline and occurrence of age-related pathologies in a number of different experimental organisms. Mutations in the Indy gene in the fruit fly, Drosophila melanogaster, dramatically extend life span without a decrease in metabolic rate, physical activity or fertility. INDY is a dicarboxylate transporter of Krebs cycle intermediates and is primarily found in the plasma membrane of midgut, fat body, and oneocytes, tissues important for intermediary metabolism in the fly. The life extending effect of reducing Indy activity has been proposed to result from changes similar to those associated with CR. We will test whether Indy long-lived mutations have induced a state of CR by comparing the mortality rate, metabolic profile (e.g. lipids, glucose, glycogen, etc.) and genomic transcriptional responses of Indy long-lived flies and calorically restricted flies. In the course of these studies we will focus on determining the physiological and molecular responses to caloric restriction that lead to life span extension in the fly in order to achieve our long-term goal of understanding the molecular genetic mechanisms underlying the process of aging.

描述（由申请人提供）：该提案的目的是确定与两种相关的寿命延长干预措施，热量限制和长期寿命的Indy突变相关的分子遗传，生化和生理变化。热量限制（CR）是提高寿命并延迟动物年龄相关症状发作的最成功的方法。 CR减慢了许多不同实验生物中与年龄相关的病理的生理下降和发生的情况。果蝇，果蝇果蝇中的Indy基因突变大大延长了寿命，而不会降低代谢率，体育活动或生育能力。 Indy是Krebs循环中间体的二羧酸盐转运蛋白，主要发现在中肠，脂肪体和Oneocytes的质膜中，对果蝇中的中间代谢很重要。已经提出，减少Indy活性的寿命扩展效应是由于与CR相似的变化所致。我们将通过比较死亡率，代谢率（例如脂质，葡萄糖，糖原等）以及Indy长寿命长蝇和热量限制的果蝇的死亡率，代谢率（例如，脂质，葡萄糖，糖原等）以及基因组转录反应来诱导CR状态。在这些研究的过程中，我们将重点介绍确定对热量限制的生理和分子反应，从而导致寿命延伸，以实现我们的长期目标，即了解衰老过程的分子遗传机制。