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

2005; Cold Spring Harbor Laboratory Press; Volume: 19; Issue: 20 Linguagem: Inglês

10.1101/gad.1352905

1549-5477

Xingxing Liu, Ning Jiang, Bryan Hughes, Eve Bigras, Eric A. Shoubridge, Siegfried Hekimi,

Mitochondrial Function and Pathology

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.