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 affect 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.
The CLK-1 protein is engaged in the biosynthesis of coenzyme Q (ubiquinone) within the mitochondria. Deficiency in the gene leads to a dietary dependence on ubiquinone and accumulation of a precursor molecule, DMQ. Neither the high levels of DMQ nor the shortage of Q, however, appears to be responsible for the physiological changes observed in clk-1 -/- mutants; furthermore, dietary supplementation with Q doesn’t rescue the lifespan phenotype — suggesting that the CLK-1 protein itself might be performing another function in the genetic determination of lifespan.
Off the reservation for a moment (i.e., meandering on my own rather than paraphrasing the authors’ thoughts): Dietary supplementation with Q confers a number of benefits on mammals, including neuroprotection and treatment of a range of cardiac dysfunctions. Could it be that high levels of (dietary) Q might shut down the biosynthetic pathway via end-product inhibition, putting CLK-1 protein to sleep and phenocopying the beneficial cellular effects of a clk-1 knockdown?
STEPANYAN, Z., HUGHES, B., CLICHE, D., CAMP, D., & HEKIMI, S. (2006). Genetic and molecular characterization of CLK-1/mCLK1, a conserved determinant of the rate of aging Experimental Gerontology, 41 (10), 940-951 DOI: 10.1016/j.exger.2006.06.041