Repeated temperature fluctuation extends the life span of Caenorhabditis elegans in a daf-16-dependent fashion.

Thermocyclers were utilized to regularly shift nematodes between 12 degrees C and 25 degrees C throughout their life spans. When wild-type worms (N2) were "thermocycled" between 12 degrees C and 25 degrees C at 10-min intervals they lived almost as long as those that were incubated constantly at 12 degrees C. Shifting at 1-min or 1-h intervals lessened this effect. Similar results were observed for the long-lived mutants daf-2, eat-2 and clk-1, each of which prolongs life span through different mechanisms. In contrast, the life span of a daf-16 mutant was not prolonged by thermocycling worms, indicating that the effect is mediated by an insulin-like signaling pathway. To elucidate the molecular basis for the life span extension, two transgenic strains were employed in which heat shock proteins (HSPs) drove expression of the green fluorescent protein (GFP) gene. As expected, both HSPs were expressed at significantly higher levels in animals grown at 25 degrees C. Moreover, HSP expression in the thermocycled worms approximated that of animals grown at 25 degrees C more so than animals grown at 12 degrees C. This suggests that incubation at the higher temperatures for short time intervals induced stress-responsive gene expression that led to significant life span extension.