美国麻省大学Mark J. Alkema和Diego Rayes等研究人员合作揭示，动物逃跑反应会通过激活胰岛素通路来损害细胞保护机制。相关论文2019年8月28日在线发表于《自然》。
研究人员发现反复诱导秀丽隐杆线虫的逃跑反应会缩短寿命，并抑制保守的细胞保护机制。逃跑反应能够激活释放酪胺的神经元，酪胺是肾上腺素和去甲肾上腺素的无脊椎动物类似物。酪胺刺激胰岛素-IGF-1信号传导途径，并通过激活肠中的肾上腺素样受体来排除应激反应基因的诱导。相比之下，长期的环境压力因素，如热或氧化应激，会减少酪胺的释放，从而可以诱导细胞保护基因。这些研究结果表明，神经应激激素在急性逃跑和长期环境应激反应之间提供了一种状态依赖性的神经转换，并为逃跑反应如何损害细胞防御系统和加速衰老提供机制见解。
据介绍，动物的压力反应需要不同的适应性策略，具体取决于压力源的性质和持续时间。尽管急性应激源（如捕食）会引起快速且能量需求的搏斗或逃跑反应，但长期环境压力因素会诱导高度保守的细胞保护过程逐渐和持久地激活。在进化谱的不同动物中，持续激活战斗或逃跑反应会削弱动物对环境挑战的抵抗力。然而，调节逃跑反应和长期压力因素之间权衡的分子和细胞机制却知之甚少。
附：英文原文
Title: The flight response impairs cytoprotective mechanisms by activating the insulin pathway
Author: Mara Jos De Rosa, Tania Veuthey, Jeremy Florman, Jeff Grant, Mara Gabriela Blanco, Natalia Andersen, Jamie Donnelly, Diego Rayes, Mark J. Alkema
Issue&Volume: 2019-08-28
Abstract: An animal’s stress response requires different adaptive strategies depending on the nature and duration of the stressor. Whereas acute stressors, such as 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 processes1,2,3. In animals across the evolutionary spectrum, continued activation of the fight-or-flight response weakens the animal’s resistance to environmental challenges4,5. However, the molecular and cellular mechanisms that regulate the trade-off between the flight response and long-term stressors are poorly understood. Here we show that repeated induction of the flight response in Caenorhabditis elegans shortens lifespan and inhibits conserved cytoprotective mechanisms. The flight response activates neurons that release tyramine, an invertebrate analogue of adrenaline and noradrenaline. Tyramine stimulates the insulin–IGF-1 signalling (IIS) pathway and precludes the induction of stress response genes by activating an adrenergic-like receptor in the intestine. By contrast, long-term environmental stressors, such as heat or oxidative stress, reduce tyramine release and thereby allow 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 defence systems and accelerates ageing.
DOI: 10.1038/s41586-019-1524-5
Source: https://www.nature.com/articles/s41586-019-1524-5
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
