A little stress usually makes the organism stronger, a concept known as hormesis. However, activation of the acute fight-or-flight response seems to actually weaken resilience. Why there is this trade-off between acute and long-term stressors is unclear. Mark Alkema, Maria José De Rosa et al. show that repeated induction of the flight response results in the neuronal release of tyramine, C. elegans' equivalent of adrenaline/noradrenaline, which puts the brakes on conserved cytoprotective pathways and shortens the worm's lifespan. De Rosa et al further demonstrate that tyramine turns on the DAF-2/Insulin/IGF-1 signalling pathway, via a G-protein coupled receptor in the intestine, which precludes induction of stress response genes. In contrast, long-term environmental stressors actually reduce tyramine release allowing the induction of these protective genes. Thus, more or less neuronal tyramine release determines whether C. elegans engages in the acute flight or long-term stress responses respectively, with profound impacts on its lifespan. Given that many of these pathways are conserved from worm to man, it will be interesting to explore whether adrenaline/noradrenaline impact health and ageing in humans via similar pathways.
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