Authors: Liu X; Jiang N; Hughes B; Bigras E; Shoubridge E; Hekimi S
Abstract: Inactivation of the Caenorhabditis elegans gene clk-1, which is required for ubiquinone biosynthesis, increases lifespan by an insulin signaling-independent mechanism. We find that homozygous inactivation of mclk1, the mouse ortholog of clk-1, yields ES cells that are protected from oxidative stress and damage to DNA. Moreover, in the livers of old mclk1(+/-) mice, hepatocytes that have lost mclk1 expression by loss of heterozygosity undergo clonal expansion, suggesting that their resistance to stress allows them to outcompete cells that still express the gene. mclk1(+/-) mice, whose growth and fertility are normal, also display a substantial increase in lifespan in each of three different genetic backgrounds. These observations indicate that the distinct mechanism by which clk-1/mclk1 affects lifespan is evolutionarily conserved from nematodes to mammals and is not tied to a particular anatomy or physiology.
Keywords: Animals; Caenorhabditis elegans/genetics/metabolism; Caenorhabditis elegans Proteins/genetics/metabolism; Crosses, Genetic; DNA Damage/genetics; Embryo, Mammalian/cytology/physiology; Embryo, Nonmammalian; *Evolution, Molecular; Hepatocytes/metabolism; Longevity/*physiology; Loss of Heterozygosity/genetics; Membrane Proteins/genetics/*metabolism; Mice; Mice, Knockout; Mitochondrial Proteins; Oxidative Stress/physiology; Stem Cells/cytology/metabolism; Ubiquinone/*biosynthesis/genetics|
Journal: Genes & development Volume: 19 Issue: 20 Pages: 2424-34 Date: Oct. 1, 2005 PMID: 16195414 |
Liu X, Jiang N, Hughes B, Bigras E, Shoubridge E, Hekimi S (2005) Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice. Genes & development 19: 2424-34.
Comment on This Data Unit