Resistance to Stress Can Be Experimentally Dissociated From Longevity

On the basis of multiple experiments demonstrating that high resistance to stress is associated with long lifespan, it has been proposed that stress resistance is a key determinant of longevity. However, the extent to which high resistance to stress is necessary or sufficient for long life is currently unclear. In this work, we use a genetic approach to disrupt different stress response pathways and examine the resulting effect on the longevity of the long-lived insulin-like growth factor 1 (IGF1) receptor mutant daf-2. Although mutation of the heat shock factor gene hsf-1, deletion of sod genes, deletion of the p38 MAPK kinase gene pmk-1, or deletion of the transcription factor gene egl-27 all resulted in decreased resistance to at least one form of stress and decreased lifespan, the magnitude of change in stress resistance did not correspond to the magnitude of change in lifespan. In addition, we found that deletion of the glycerol-3-phosphate dehydrogenase genes gpdh-1 and gpdh-2 or deletion of the DAF-16 cofactor gene nhl-1 also results in decreased resistance to at least one form of stress but increases lifespan. Overall, our results suggest that while increased stress resistance is associated with longevity, stress resistance, and lifespan can be experimentally dissociated.