Genetic and molecular characterization of CLK-1/mCLK1, a conserved determinant of the rate of aging.
The clk-1 gene of the nematode Caenorhabditis elegans encodes an evolutionarily conserved enzyme that is necessary for ubiquinone biosynthesis. Loss-of-function mutations in clk-1, as well as in its mouse orthologue mclk1, increase lifespan in both organisms. In nematodes, clk-1 extends lifespan by a mechanism that is distinct from the insulin signaling-like pathway but might have similarities to calorie restriction. The evolutionary conservation of the effect of clk-1/mclk1 on lifespan suggests that the gene affects a fundamental mechanism of aging. The clk-1/mclk1 system could allow for the understanding of this mechanism by combining genetic and molecular investigations in worms with studies in mice, where age-dependent disease processes relevant to human health can be modeled.
Stepanyan
Zaruhi
Z
Department of Biology, McGill University, Montréal, Que., Canada.
Hughes
Bryan
B
Cliche
Dominic O
DO
Camp
Darius
D
Hekimi
Siegfried
S
D000375:Aging / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D004032:Diet; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008136:Longevity / Q000235:genetics; D019656:Loss of Heterozygosity / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D006899:Mixed Function Oxygenases; D009154:Mutation; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013696:Temperature; D014451:Ubiquinone / Q000008:administration & dosage / Q000096:biosynthesis / Q000378:metabolism
C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D006899:Mixed Function Oxygenases; C434481:Coq7 protein, mouse