Mutations that prolong the life span of worms also suppress tumor formation, report Julie Pinkston, Cynthia Kenyon, and colleagues (University of California, San Francisco).
Mutations in the gld-1 gene of Caenorhabditis elegans cause germ cells to proliferate uncontrollably, giving rise to lethal tumors. In most organisms, tumor susceptability increases with age, so Pinkston et al. were interested in how mutations that increase the life span of C. elegans might affect gld-1 mutant worms.
Four different mutations that each promote longevity also suppressed tumorigenesis. When gld-1 worms carried mutations in daf-2, eat-2, isp-1, or clk-1 genes, the proliferation rate of germ line tumor cells was dramatically reduced. Remarkably, however, none of these mutations affected the proliferation rate of germ cells in worms without the gld-1 mutation.
Mutations in daf-2 interfere with insulin signaling, eat-2 mutations restrict calorie intake, and isp-1 and clk-1 mutations impair mitochondrial activity. These apparently diverse routes may lead to both longevity and protection against cancer by limiting energy or nutrient availability to cells, says Kenyon.
In normal worms, the mutations do not cause nutrients to fall below levels necessary for cell division. In rapidly growing tumor cells, however, the demand for nutrients is higher. The mutations may then be sufficient to starve the tumor cells, inducing a stress response that ultimately shuts down the cell cycle machinery.