Reduced insulin/insulin-like growth factor signaling decreases translation in Drosophila and mice.
Reduced insulin/insulin-like growth factor signaling decreases translation in Drosophila and mice.
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DOI：
10.1038/srep30290
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发表时间：
2016-07-25
影响因子：
4.6
通讯作者：
Partridge L
中科院分区：
文献类型：
--
作者：
Essers P;Tain LS;Nespital T;Goncalves J;Froehlich J;Partridge L
下调胰岛素/胰岛素样生长因子信号通路（IIS）可延长C.线虫、果蝇和小鼠。In C.在线虫中，IIS减少导致翻译下调，这本身可以延长寿命。然而，在其他多细胞生物中，减少IIS对翻译的影响尚未确定。使用两种长寿的IIS模型，即缺乏三种胰岛素样肽（dilp 2 - 3，5-/-）的果蝇和缺乏胰岛素受体底物1（Irs 1-/-）的小鼠，以及两种独立的翻译测定，多核糖体分析和放射性标记的氨基酸掺入，我们表明，减少IIS降低这些生物体的翻译。在果蝇中，减少IIS降低了脂肪体和肠道中的多核糖体水平，但仅降低了脂肪体中的蛋白质合成速率。小鼠中IIS减少仅在骨骼肌中降低蛋白质合成速率，而不减少任何组织中的多聚体。肌肉中这种降低的翻译与肌肉本身的Irs 1损失无关，但这是肝脏中Irs 1损失的继发效应。总之，下调翻译是一种进化保守的反应，以减少IIS，但它发生的组织可以不同的生物体。此外，降低翻译的机制可能在小鼠中不同，可能与调控过程的复杂性有关。
Down-regulation of insulin/insulin-like growth factor signaling (IIS) can increase lifespan in C. elegans, Drosophila and mice. In C. elegans, reduced IIS results in down-regulation of translation, which itself can extend lifespan. However, the effect of reduced IIS on translation has yet to be determined in other multicellular organisms. Using two long-lived IIS models, namely Drosophila lacking three insulin-like peptides (dilp2-3,5−/−) and mice lacking insulin receptor substrate 1 (Irs1−/−), and two independent translation assays, polysome profiling and radiolabeled amino acid incorporation, we show that reduced IIS lowers translation in these organisms. In Drosophila, reduced IIS decreased polysome levels in fat body and gut, but reduced the rate of protein synthesis only in the fat body. Reduced IIS in mice decreased protein synthesis rate only in skeletal muscle, without reducing polysomes in any tissue. This lowered translation in muscle was independent of Irs1 loss in the muscle itself, but a secondary effect of Irs1 loss in the liver. In conclusion, down-regulation of translation is an evolutionarily conserved response to reduced IIS, but the tissues in which it occurs can vary between organisms. Furthermore, the mechanisms underlying lowered translation may differ in mice, possibly associated with the complexity of the regulatory processes.