Genetic and molecular characterization of CLK-1/mCLK1, a conserved determinant of the rate of aging

• Published in: Experimental gerontology 2006-10, Vol.41 (10), p.940-951
• Main Authors: Stepanyan, Zaruhi, Hughes, Bryan, Cliche, Dominic O., Camp, Darius, Hekimi, Siegfried
• Format: Article
• Language: English
• Subjects: Age-dependent disease; Aging; Aging - genetics; Animals; C. elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins - genetics; clk-1; Co-enzyme Q; Diet; Evolutionary conservation; Humans; Lifespan; Lipid Metabolism - genetics; Longevity - genetics; Loss of Heterozygosity - genetics; mclk1; Membrane Proteins - genetics; Mice; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Mouse; Mutation; Phenotype; Reactive Oxygen Species - metabolism; Signal Transduction - genetics; Temperature; Ubiquinone; Ubiquinone - administration & dosage; Ubiquinone - biosynthesis; Ubiquinone - metabolism
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2006.06.041

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.