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The flight response impairs cytoprotective mechanisms by activating the insulin pathway

An animal’s stress response requires different adaptive strategies depending on the nature and duration of the stressor. While acute stressors, like predation, induce a rapid and energy-demanding fight or flight response, long-term environmental stressors induce the gradual and long-lasting activati...

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Autores principales: José De Rosa, María, Veuthey, Tania, Florman, Jeremy, Grant, Jeff, Blanco, María Gabriela, Andersen, Natalia, Donnelly, Jamie, Rayes, Diego, Alkema, Mark J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986477/
https://www.ncbi.nlm.nih.gov/pubmed/31462774
http://dx.doi.org/10.1038/s41586-019-1524-5
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author José De Rosa, María
Veuthey, Tania
Florman, Jeremy
Grant, Jeff
Blanco, María Gabriela
Andersen, Natalia
Donnelly, Jamie
Rayes, Diego
Alkema, Mark J.
author_facet José De Rosa, María
Veuthey, Tania
Florman, Jeremy
Grant, Jeff
Blanco, María Gabriela
Andersen, Natalia
Donnelly, Jamie
Rayes, Diego
Alkema, Mark J.
author_sort José De Rosa, María
collection PubMed
description An animal’s stress response requires different adaptive strategies depending on the nature and duration of the stressor. While acute stressors, like predation, induce a rapid and energy-demanding fight or flight response, long-term environmental stressors induce the gradual and long-lasting activation of highly conserved cytoprotective processes(1–3). In animals across the evolutionary spectrum the continued activation of the fight-or-flight response weakens the animal’s resistance to environmental challenges(4,5). However, the molecular and cellular mechanisms that regulate the trade-off between flight response and long-term stressors are poorly understood. Here we show that repeated induction of the C. elegans flight response shortens lifespan and inhibits conserved cytoprotective mechanisms. The flight response activates neurons that release tyramine, the invertebrate analog of adrenaline/noradrenaline. Tyramine stimulates the DAF-2/Insulin/IGF-1 pathway and precludes the induction of stress response genes by activating an adrenergic-like receptor in the intestine. In contrast, long-term environmental stressors, such as heat or oxidative stress, reduce tyramine release allowing the induction of cytoprotective genes. These findings demonstrate that a neural stress-hormone supplies a state-dependent neural switch between acute flight and long-term environmental stress responses and provides mechanistic insights into how the flight response impairs cellular defense systems and accelerates aging.
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spelling pubmed-79864772021-03-23 The flight response impairs cytoprotective mechanisms by activating the insulin pathway José De Rosa, María Veuthey, Tania Florman, Jeremy Grant, Jeff Blanco, María Gabriela Andersen, Natalia Donnelly, Jamie Rayes, Diego Alkema, Mark J. Nature Article An animal’s stress response requires different adaptive strategies depending on the nature and duration of the stressor. While acute stressors, like predation, induce a rapid and energy-demanding fight or flight response, long-term environmental stressors induce the gradual and long-lasting activation of highly conserved cytoprotective processes(1–3). In animals across the evolutionary spectrum the continued activation of the fight-or-flight response weakens the animal’s resistance to environmental challenges(4,5). However, the molecular and cellular mechanisms that regulate the trade-off between flight response and long-term stressors are poorly understood. Here we show that repeated induction of the C. elegans flight response shortens lifespan and inhibits conserved cytoprotective mechanisms. The flight response activates neurons that release tyramine, the invertebrate analog of adrenaline/noradrenaline. Tyramine stimulates the DAF-2/Insulin/IGF-1 pathway and precludes the induction of stress response genes by activating an adrenergic-like receptor in the intestine. In contrast, long-term environmental stressors, such as heat or oxidative stress, reduce tyramine release allowing the induction of cytoprotective genes. These findings demonstrate that a neural stress-hormone supplies a state-dependent neural switch between acute flight and long-term environmental stress responses and provides mechanistic insights into how the flight response impairs cellular defense systems and accelerates aging. 2019-08-28 2019-09 /pmc/articles/PMC7986477/ /pubmed/31462774 http://dx.doi.org/10.1038/s41586-019-1524-5 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
José De Rosa, María
Veuthey, Tania
Florman, Jeremy
Grant, Jeff
Blanco, María Gabriela
Andersen, Natalia
Donnelly, Jamie
Rayes, Diego
Alkema, Mark J.
The flight response impairs cytoprotective mechanisms by activating the insulin pathway
title The flight response impairs cytoprotective mechanisms by activating the insulin pathway
title_full The flight response impairs cytoprotective mechanisms by activating the insulin pathway
title_fullStr The flight response impairs cytoprotective mechanisms by activating the insulin pathway
title_full_unstemmed The flight response impairs cytoprotective mechanisms by activating the insulin pathway
title_short The flight response impairs cytoprotective mechanisms by activating the insulin pathway
title_sort flight response impairs cytoprotective mechanisms by activating the insulin pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986477/
https://www.ncbi.nlm.nih.gov/pubmed/31462774
http://dx.doi.org/10.1038/s41586-019-1524-5
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