Ab'/> Integrated stress response stimulates FGF21 expression: Systemic enhancer of longevity
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Integrated stress response stimulates FGF21 expression: Systemic enhancer of longevity

机译：综合应力反应刺激FGF21表达：寿命的全身增强剂

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AbstractFGF21 is a multifunctional metabolic and stress hormone which is normally expressed in liver but cellular stress, e.g. mitochondrial or endoplasmic reticulum (ER) stress, can induce its expression and subsequent secretion from several mammalian tissues. The stress kinases of the integrated stress response (ISR) pathway stimulate the expression of FGF21 through the activation of ATF4 transcription factor, thus enhancing cellular stress resistance. The metabolic and stress-inducible transactivation mechanisms ofFGF21gene are mostly mediated through separate pathways. FGF21 is an interorgan regulator which can alleviate many age-related metabolic and stress disorders, e.g. through the activation of AMPK signaling. FGF21 signaling is also involved in circadian and torpor regulation. Given that circulating FGF21 can attenuate organelle stress, e.g. mitochondrial and ER stresses, it resembles a stress-induced cell non-autonomous regulation of proteostasis and longevity present in model organisms. The overexpression of FGF21 can even extend the lifespan of mice, probably by improving the healthspan. We will clarify the positive and negative signaling mechanisms which control the stress-related expression of FGF21 through the ISR pathway. Moreover, we will examine the role of FGF21 as an interorgan coordinator of survival functions in metabolic and stress disorders. We conclude that FGF21 can be viewed as a cell non-autonomous enhancer of longevity in mammals.
机译：<！[cdata [ 抽象 FGF21是一种多功能代谢和应激激素，其通常在肝脏中表达但细胞应力，例如线粒体或内质网（ER）应激，可以诱导其表达和随后的几种哺乳动物组织的分泌。综合应力响应（ISR）途径的应力激酶通过ATF4转录因子的激活刺激FGF21的表达，从而提高细胞应激性。 FGF21 基因的代谢和应激诱导型转基因机制主要通过单独的途径介导。 FGF21是一种室同期调节剂，可以缓解许多与年龄相关的代谢和压力障碍，例如，通过激活AMPK信号传导。 FGF21信令也涉及昼夜节律和托河调节。鉴于循环FGF21可以衰减细胞器应力，例如，线粒体和ER应力，它类似于在模型生物中存在的应激诱导的细胞非自主调节蛋白质和寿命。 FGF21的过表达甚至可以延长小鼠的寿命，可能是通过改善卫生钢。我们将阐明通过ISR途径控制FGF21的应力相关表达的正极和负信号机制。此外，我们将研究FGF21作为代谢和应激障碍中生存功能的中东性协调器的作用。我们得出结论，FGF21可以被视为哺乳动物中寿命的细胞非自主增强剂。

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