The Mental Health Research Institute, Parkville, Victoria, Australia.
Cell Metab. 2010 Sep 8;12(3):260-72. doi: 10.1016/j.cmet.2010.08.004.
The insulin-like signaling (ILS) pathway regulates metabolism and is known to modulate adult life span in C. elegans. Altered stress responses and resistance to a wide range of stressors are also associated with changes in ILS and contribute to enhanced longevity. The transcription factors DAF-16 and HSF-1 are key effectors of the longevity phenotype. We demonstrate that increased intrinsic thermotolerance, due to lower ILS, is not dependent on stress-induced transcriptional responses but instead requires active protein translation. Translation profiling experiments reveal genes that are posttranscriptionally regulated in response to altered ILS during heat shock in a DAF-16-dependent manner. Furthermore, several novel proteins are specifically required for ILS effects on thermotolerance. We propose that lowered ILS results in metabolic and physiological changes. These DAF-16-induced changes precondition a translational response under acute stress to modulate survival.
胰岛素样信号（ILS）通路调节代谢，已知可调节秀丽隐杆线虫的成年寿命。改变的应激反应和对多种应激源的抗性也与 ILS 的变化有关，并有助于延长寿命。转录因子 DAF-16 和 HSF-1 是长寿表型的关键效应因子。我们证明，由于 ILS 降低而导致的内在耐热性增加，不依赖于应激诱导的转录反应，而是需要活跃的蛋白质翻译。翻译谱分析实验揭示了在热休克期间，由于 ILS 改变，以 DAF-16 依赖的方式进行转录后调控的基因。此外，几种新的蛋白质特异性地需要 ILS 对耐热性的影响。我们提出，ILS 的降低导致代谢和生理变化。这些 DAF-16 诱导的变化预先调节急性应激下的翻译反应，以调节存活。
