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coq7/clk-1was isolated from a long-lived mutant ofCaenorhabditis elegans, and shows sluggish behaviours and an extended lifespan. InC. elegansandSaccharomyces cerevisiae,coq7/clk-1is required for the biosynthesis of coenzyme Q (CoQ), an essential co-factor in mitochondrial respiration. Theclk-1mutant contains dietary CoQ8 fromEscherichia coliand demethoxyubiquinone 9 (DMQ9) instead of CoQ9. In a previous study, we generated COQ7-deficient mice by targeted disruption of thecoq7gene and reported that mousecoq7/clk-1is also essential for CoQ synthesis, maintenance of mitochondrial integrity and neurogenesis. In the present study, we rescued COQ7-deficient mice from embryonic lethality and established a mouse model with decreased CoQ level by transgene expression of COQ7/CLK-1. A biochemical analysis showed a concomitant decrease in CoQ9, mitochondrial respiratory enzyme activity and the generation of reactive oxygen species (ROS) in the mitochondria of CoQ-insufficient mice. This implied that the depressed activity of respiratory enzymes and the depressed production of ROS may play a physiological role in the control of lifespan in mammalian species and ofC. elegans. [ABSTRACT FROM AUTHOR]