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Hormesis in Caenorhabditis elegans dauer-defective mutants.

Cypser JR, Johnson TE.
Institute for Behavioral Genetics, University of Colorado, Box 447, Boulder, CO 80309, USA. James_Cypser@brown.edu

We have shown that increased longevity and stress resistance can be induced by sub-lethal exposure to stressors (hormesis). Here we ask whether genes of the dauer formation pathway that are known to modulate life span in Caenorhabditis elegans are required for this hormesis. We find that loss-of-function mutations in any of three genes (daf-16, daf-18, or daf-12) not only reduce or abolish the ability to form dauers but also block the hormetic response increasing life span following sub-lethal heat stress. Indeed, the life expectancy of these dauer-defective mutants is decreased by the same pretreatments that increase the life expectancy of wild-type animals. Additionally, we find that daf-16 and daf-12 are not required for the induction of thermotolerance, but daf-18 is required for its full induction. Our results underscore the importance of the dauer-formation pathway in specifying life span by demonstrating a similar, but not identical, role in life extension attributed to hormesis.