COENZYME Q AND AGING IN CAENORHABDITIES ELEGANS

线虫秀丽线虫已被用作衰老遗传学研究的模型。线虫的Clock-1(CLK-1)基因突变会导致发育减慢和行为节律，并延长寿命。线虫CLK-1基因是酿酒酵母中辅酶Q合成辅酶Q所必需的COQ7基因的同源物。线虫、大鼠和人的CLK-1/COQ7同源物都在酵母coq7缺失突变体中恢复辅酶Q的生物合成。鉴于酵母、大鼠、人和线虫CLK-1/Coq7多肽的功能保守，测试辅酶Q水平的变化是否可能是线虫模型中发育缓慢、行为和衰老速度的原因是至关重要的。本研究旨在回答以下问题：(1)CLK-1基因突变是否会影响线虫体内辅酶Q的水平？(2)线虫CLK-1突变体在缺乏辅酶Q的大肠杆菌上生长是否会影响线虫的发育速度、成虫行为或寿命？以及(3)线虫coq零突变体的表型是什么？为了检验这些问题，CLK-1突变株和野生型菌株的辅酶Q水平、发育时间和寿命将作为类型大肠杆菌食物来源的函数来确定；辅酶Q充足和辅酶Q缺乏的大肠杆菌菌株都将被使用。这些研究将确定CLK-1突变对线虫系统中辅酶Q生物合成的影响；这是一个评估辅酶Q与衰老关系的理想模型。这些研究也可能表明线虫是否能提供一种后生动物模型，特别适合于解决有关辅酶Q的摄取、代谢和再分配的问题。

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.