CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans

Mutations in the clk-1 gene of the nematode Caenorhabditis elegans result i n an average slowing of a variety of developmental and physiological proces ses, including the cell cycle, embryogenesis, post-embryonic growth, rhythm ic behaviors and aging. In yeast, a CLK-1 homologue is absolutely required for ubiquinone biosynthesis and thus respiration. Here we show that CLK-1 i s fully active when fused to green fluorescent protein and is found in the mitochondria of all somatic cells. The activity of mutant mitochondria, how ever, is only very slightly impaired, as measured ill vivo by a dye-uptake assay, and in vitro by the activity of succinate cytochrome c reductase, Ov erexpression of CLK-1 activity in mild-type worms can increase mitochondria l activity, accelerate behavioral rates during aging acid shorten life span , indicating that clk-1 regulates and controls these processes. These obser vations also provide strong genetic evidence that mitochondria are causally involved in aging. Furthermore, the reduced respiration of the long-lived clk-1 mutants suggests that longevity is promoted by the age-dependent decr ease in mitochondrial function that is observed in most species.