COENZYME Q AND AGING IN CAENORHABDITIES ELEGANS

辅酶 Q 与线虫衰老

• 批准号: 6129868
• 负责人: CATHERINE FREITAG CLARKE
• 金额: $ 7.65万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6129868
• 关键词: Caenorhabditis elegans; Escherichia coli; aging; bioperiodicity; biosynthesis; gene induction /repression; genetically modified animals; lipids; mutant; nutrient bioavailability; ubiquinone

The nematode Caenorhabditis elegans has been used as a model for the genetic studies of aging. Mutations in the Clock-1 (clk-1) gene of C. elegans result in slowed development and rhythmic behaviors, and an extended life span. The C. elegans clk-1 gene is a homologue of COQ7, a gene in Saccharomyces cerevisiae required for the biosynthesis of ubiquinone (coenzyme Q). The nematode, rat and human homologs of clk-1/COQ7 all function to restore coenzyme Q biosynthesis in the yeast coq7 null mutant. Given the functional conservation of yeast rat, human and C. elegans CLK-1/Coq7 polypeptides, it is crucial to test whether changes in the level of coenzyme Q may be responsible for the slowed development, behavior and rate of aging in the nematode model. The studies proposed are designed to answer the following questions: (1) Do mutations in the clk-1 gene have effects on the level of coenzyme Q in C. elegans? (2) Are rates of development, adult behaviors, or life span affected when the C. elegans clk-1 mutants are grown on E. coli lacking coenzyme Q? and (3) What is the phenotype of a C. elegans coq null mutant? In order to examine these questions, the levels of coenzyme Q, the developmental timing, and the life span of the clk-1 mutant and wild type strains will be determined as a function of the type E. coli food source; both coenzyme Q-replete and coenzyme Q- deficient E. coli strains will be used. These studies will determine the effect of the clk-1 mutations on the biosynthesis of coenzyme Q in the nematode system; a model that is ideal for evaluating the relationship between coenzyme Q and aging. It is also likely that these studies will indicate whether C. elegans can provide a metazoan model uniquely suited to address questions regarding coenzyme Q uptake, metabolism and redistribution.

线虫秀丽隐杆线虫已被用作衰老遗传研究的模型。 秀丽隐杆线虫的时钟1（CLK-1）基因中的突变导致发育速度减慢和节奏行为，并延长了寿命。 秀丽隐杆线虫CLK-1基因是coq7的同源物，coq7是泛素酮生物合成所需的酿酒酵母基因（辅酶Q）。 CLK-1/COQ7的线虫，大鼠和人类同源物均功能恢复酵母COQ7 NULL突变体中的辅酶Q生物合成。鉴于酵母大鼠，人和秀丽隐杆线虫CLK-1/COQ7多肽的功能保护，对于测试辅酶Q水平的变化是否可能导致线虫模型中的发育，行为和衰老速度放缓，至关重要。 提出的研究旨在回答以下问题：（1）CLK-1基因中的突变是否对秀丽隐杆线虫中的辅酶Q水平有影响？ （2）当秀丽隐杆线虫CLK-1突变体在缺乏辅酶Q的大肠杆菌上生长时，发育率，成人行为或生命跨度是否会影响？ （3）秀丽隐杆线虫coq null突变体的表型是什么？ 为了检查这些问题，辅酶Q的水平，发育时机以及CLK-1突变体和野生型菌株的寿命将被确定为E. Coli型食品源的函数；辅酶Q复发和辅酶Q-缺陷大肠杆菌菌株均应使用。 这些研究将确定CLK-1突变对线虫系统中辅酶Q的生物合成的影响。一个理想的模型，用于评估辅酶Q与老化之间的关系。 这些研究也可能表明秀丽隐杆线虫是否可以提供一个非常适合解决有关辅酶Q摄取，代谢和再分配的问题。