Although certain methods of lowering and/or altering mRNA translation are associated with increased lifespan, the mechanisms underlying this effect remain largely unknown. We previously showed that the increased lifespan conferred by reducing expression of eukaryotic translation initiation factor 4G (eIF4G/IFG‐1) enhances survival under starvation conditions while shifting protein expression toward factors involved with maintaining ER‐dependent protein and lipid balance. In this study, we investigated changes in ER homeostasis and found that lower eIF4G/IFG‐1 increased survival under conditions of ER stress. Enhanced survival required the ER stress sensor gene ire‐1 and the ER calcium ATPase gene sca‐1 and corresponded with increased translation of chaperones that mediate the ER unfolded protein response (UPR^ER). Surprisingly, the heat‐shock transcription factor gene hsf‐1 was also required for enhanced survival, despite having little or no influence on the ability of wild‐type animals to survive ER stress. The requirement for hsf‐1 led us to re‐evaluate the role of eIF4G/IFG‐1 on thermotolerance. Results show that lowering expression of this translation factor enhanced thermotolerance, but only after prolonged attenuation, the timing of which corresponded to increased transcription of heat‐shock factor transcriptional targets. Results indicate that restricting overall translation through eIF4G/IFG‐1 enhances ER and cytoplasmic proteostasis through a mechanism that relies heavily on hsf‐1.

中文翻译：

---

通过eIF4G / IFG-1减少翻译可提高秀丽隐杆线虫中依赖于热休克因子HSF-1的内质网应激条件下的存活率。

尽管降低和/或改变mRNA翻译的某些方法与使用寿命的延长有关，但这种作用的机制仍是未知之数。我们先前表明，通过减少真核翻译起始因子4G（eIF4G / IFG-1）的表达而延长的寿命可以提高饥饿条件下的存活率，同时将蛋白质表达转移到与维持ER依赖性蛋白质和脂质平衡有关的因子上。在这项研究中，我们研究了内质网稳态的变化，发现较低的eIF4G / IFG-1可以增加内质网应激条件下的存活率。为了提高生存率，需要ER压力传感器基因ire-1和ER钙ATPase基因sca-1并与介导ER未折叠蛋白反应（UPR ^ER）的伴侣的翻译增加相对应。出乎意料的是，尽管对野生型动物抵抗内质网应激的能力几乎没有影响，热休克转录因子基因hsf-1也需要增强存活率。HSF-1的要求使我们重新评估了eIF4G / IFG-1在耐热性方面的作用。结果表明，降低该翻译因子的表达可提高耐热性，但仅在延长的衰减后才出现，其时间与热休克因子转录靶的转录增加相对应。结果表明，通过eIF4G / IFG-1限制整体翻译可通过高度依赖hsf-1的机制增强ER和细胞质蛋白变性。