Increased Resistance to Cellular Stress Common to Many Forms of Induced Longevity
An open access paper, and an example of the way in which researchers are closing in on common mechanisms that explain the operation of many diverse ways found to extend healthy life in laboratory animals: "Many mutations that increase animal lifespan also confer stress tolerance, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of individual cytoprotective pathways is essential for lifespan extension, or merely correlated. To establish whether the regulatory pathways for the induction of cytoprotective responses are key in the extension of lifespan, we performed an RNAi screen for gene inactivations that decouple the activation of cytoprotective pathways from xenobiotic stimuli that normally induce them. The screen identified 29 genes that constitute the regulatory cascades of the unfolded protein response, oxidative stress response, and detoxification. ... If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction ... We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension."