Evolutionary Conservation Of A Mechanism Of Longevity From Worms To Mammals

The gene clk-1 in the worm, as well as mclk1 in mice, encodes an enzymenecessary for the biosynhesis of ubiquinone, an essential cofactor innumerous redox reactions such as mitochondrial respiration. Though lackof the mclk1 gene results in embryonic lethality, the authors were ableto study mclk1-/- embryonic stem (ES) cells and show that they areresistant to oxidative stress and exhibit reduced DNA damage whencompared to ES cells in which this gene is active.

Because these findings would predict that reduced expression of themclk1 gene would result in longevity, the authors compared the lifespanof mice heterozygous for mclk1 with their wild-type counterparts. Apredicted, mclk1+/- mice displayed a substantial increase in lifespanin three different genetic backgrounds tested. Moreover, when thelivers of these mice where analyzed, the authors found that a subset ofhepatocytes exhibited loss of heterozygosity (effectively becomingmclk1-/- cells) and had undergone clonal expansion. The authors suggestthat these mclk null cells were able to out-compete mclk1+/-hepatocytes, suggesting that resistance to oxidative stress upon lossof mclk1 provides a growth advantage.

Though the aging process of different organisms will most likely differdue to different physiologies and environments, Dr. Hekimi summarizesthe relevance of their findings by concluding that "... thelongevity-promoting effect of reducing clk-1/mclk1 activity that wasinitially observed in C. elegans is conserved in mice, supporting theidea that some molecular mechanisms of aging are shared throughout theanimal kingdom."