Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice

Genes Dev. 2005 Oct 15;19(20):2424-34. doi: 10.1101/gad.1352905. Epub 2005 Sep 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Crosses, Genetic
  • DNA Damage / genetics
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / physiology
  • Embryo, Nonmammalian
  • Evolution, Molecular*
  • Hepatocytes / metabolism
  • Longevity / physiology*
  • Loss of Heterozygosity / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Mitochondrial Proteins
  • Mixed Function Oxygenases
  • Oxidative Stress / physiology
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Ubiquinone / biosynthesis*
  • Ubiquinone / genetics


  • CLK-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • Mitochondrial Proteins
  • Ubiquinone
  • Mixed Function Oxygenases
  • Coq7 protein, mouse