論文 - 詳細
| RRC ID | 59477 |
|---|---|
| 著者 | De Rosa MJ, Veuthey T, Florman J, Grant J, Blanco MG, Andersen N, Donnelly J, Rayes D, Alkema MJ. |
| タイトル | The flight response impairs cytoprotective mechanisms by activating the insulin pathway. |
| ジャーナル | Nature |
| 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 processes1-3. 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. |
| 巻・号 | 573(7772) |
| ページ | 135-138 |
| 公開日 | 2019-9-1 |
| DOI | 10.1038/s41586-019-1524-5 |
| PII | 10.1038/s41586-019-1524-5 |
| PMID | 31462774 |
| PMC | PMC7986477 |
| MeSH | Active Transport, Cell Nucleus Animals Caenorhabditis elegans / cytology* Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism Cell Nucleus / metabolism Cytoprotection* Forkhead Transcription Factors / metabolism Insulin / metabolism* Insulin-Like Growth Factor I / metabolism Intestinal Mucosa / metabolism Longevity Neurons / metabolism Receptors, Adrenergic / metabolism Receptors, Catecholamine / metabolism Signal Transduction Stress, Psychological Tyramine / metabolism* |
| IF | 43.07 |
| 引用数 | 3 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 90 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm2913 tm1815 tm1846 |