The gene clk-1 in the worm, as well as mclk1 in mice, encodes an enzyme necessary for the biosynhesis of ubiquinone, an essential cofactor in numerous redox reactions such as mitochondrial respiration. Though lack of the mclk1 gene results in embryonic lethality, the authors were able to study mclk1-/- embryonic stem (ES) cells and show that they are resistant to oxidative stress and exhibit reduced DNA damage when compared to ES cells in which this gene is active.
Because these findings would predict that reduced expression of the mclk1 gene would result in longevity, the authors compared the lifespan of mice heterozygous for mclk1 with their wild-type counterparts. A predicted, mclk1+/- mice displayed a substantial increase in lifespan in three different genetic backgrounds tested. Moreover, when the livers of these mice where analyzed, the authors found that a subset of hepatocytes exhibited loss of heterozygosity (effectively becoming mclk1-/- cells) and had undergone clonal expansion. The authors suggest that these mclk null cells were able to out-compete mclk1+/- hepatocytes, suggesting that resistance to oxidative stress upon loss of mclk1 provides a growth advantage.
Though the aging process of different organisms will most likely differ due to different physiologies and environments, Dr. Hekimi summarizes the relevance of their findings by concluding that "�the longevity-promoting effect of reducing clk-1/mclk1 activity that was initially observed in C. elegans is conserved in mice, supporting the idea that some molecular mechanisms of aging are shared throughout the animal kingdom."