| First Author | Liu X | Year | 2005 |
| Journal | Genes Dev | Volume | 19 |
| Issue | 20 | Pages | 2424-34 |
| PubMed ID | 16195414 | Mgi Jnum | J:102109 |
| Mgi Id | MGI:3606819 | Doi | 10.1101/gad.1352905 |
| Citation | Liu X, et al. (2005) Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice. Genes Dev 19(20):2424-34 |
| abstractText | 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. |
