The flight response impairs cytoprotective mechanisms by activating the insulin pathway.
The flight response impairs cytoprotective mechanisms by activating the insulin pathway.
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DOI：
10.1038/s41586-019-1524-5
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发表时间：
2019-09
期刊：
影响因子：
64.8
通讯作者：
Alkema MJ
中科院分区：
文献类型：
--
作者：
De Rosa MJ;Veuthey T;Florman J;Grant J;Blanco MG;Andersen N;Donnelly J;Rayes D;Alkema MJ
动物的应激反应需要不同的适应策略，这取决于应激源的性质和持续时间。虽然急性应激源，如捕食，诱导快速和能量需求的战斗或逃跑反应，长期的环境应激源诱导高度保守的细胞保护过程的逐渐和持久的激活。在整个进化谱系的动物中，战斗或逃跑反应的持续激活削弱了动物对环境挑战的抵抗力。然而，调节飞行反应和长期应激之间的权衡的分子和细胞机制知之甚少。在这里，我们表明，重复诱导C。elegans飞行反应缩短寿命并抑制保守的细胞保护机制。飞行反应激活神经元，释放酪胺，肾上腺素/去甲肾上腺素的无脊椎动物类似物。酪胺通过激活肠道中的肾上腺素样受体，刺激β 2/胰岛素/IGF-1通路，并阻止应激反应基因的诱导。相反，长期的环境压力，如热或氧化应激，减少酪胺释放，允许诱导细胞保护基因。这些研究结果表明，神经应激激素在急性飞行和长期环境应激反应之间提供了一种状态依赖性神经开关，并提供了飞行反应如何损害细胞防御系统和加速衰老的机制见解。
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. In animals across the evolutionary spectrum the continued activation of the fight-or-flight response weakens the animal’s resistance to environmental challenges. 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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影响因子：
2.7
作者：
Kagawa-Nagamura Y;Gengyo-Ando K;Ohkura M;Nakai J
通讯作者：
Nakai J
影响因子：
3.7
作者：
Lee IR;Lim JW;Ormerod KL;Morrow CA;Fraser JA
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Fraser JA
DOI：
10.1073/pnas.1009300107
发表时间：
2010-08-31
影响因子：
11.1
作者：
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通讯作者：
Schmitz, Oswald J.
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作者：
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通讯作者：
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影响因子：
16.2
作者：
Alkema, MJ;Hunter-Ensor, M;Horvitz, HR
通讯作者：
Horvitz, HR