Braeckman Bart P, Houthoofd Koen, Brys Kristel, Lenaerts Isabelle, De Vreese Annemie, Van Eygen Sylvie, Raes Hilda, Vanfleteren Jacques R
Department of Biology, Ghent University, K L Ledeganckstraat 35, B-9000, Ghent, Belgium.
Mech Ageing Dev. 2002 Sep;123(11):1447-56. doi: 10.1016/s0047-6374(02)00085-4.
Mutation in any of the four clock genes (clk-1, clk-2, clk-3, gro-1) causes an average slowing down of many temporal processes, and an increase of mean life span. The latter effect has been linked to the slow phenotype, and it has been reasoned that any reduction of the rate of living would reduce the load of oxidative damage, which is thought to drive the ageing process. To test this model we measured several parameters describing metabolic output in wild type worms and all four Clk mutants. We found no gross changes in metabolic output, as assessed from oxygen consumption and heat production rates, lucigenin-mediated light production capacity, ATP content, and lipofuscin autofluorescence. Catalase and superoxide dismutase (SOD) were variably altered, but not cooperatively, as would be expected to enhance reactive oxygen species (ROS) scavenging activity. Thus we conclude that the prolonged life span of Clk mutants cannot be attributed to reduced metabolic rate or an increased activity of the major antioxidant enzymes catalase and SOD.
四个生物钟基因（clk-1、clk-2、clk-3、gro-1）中任何一个发生突变，都会导致许多时间进程平均放缓，并延长平均寿命。后一种效应与缓慢的表型有关，据推测，任何生活速率的降低都会减少氧化损伤的负荷，而氧化损伤被认为是驱动衰老过程的因素。为了验证这一模型，我们测量了描述野生型线虫和所有四种Clk突变体代谢输出的几个参数。根据氧气消耗率、产热率、光泽精介导的发光能力、ATP含量和脂褐素自发荧光评估，我们发现代谢输出没有明显变化。过氧化氢酶和超氧化物歧化酶（SOD）发生了不同程度的改变，但并非协同改变，而如果要增强活性氧（ROS）清除活性，它们应该协同改变。因此，我们得出结论，Clk突变体寿命的延长不能归因于代谢率降低或主要抗氧化酶过氧化氢酶和SOD的活性增加。
