PDF(Pubmed)
Abstract：
Temperature is a critical environmental cue that controls the development and lifespan of many animal species; however, mechanisms underlying low-temperature adaptation are poorly understood. Here, we describe cold-inducible diapause (CID), another type of diapause induced by low temperatures in Caenorhabditis elegans. A premature stop codon in heat shock factor 1 (hsf-1) triggers entry into CID at 9 °C, whereas wild-type animals enter CID at 4 °C. Furthermore, both wild-type and hsf-1(sy441) mutant animals undergoing CID can survive for weeks, and resume growth at 20 °C. Using epistasis analysis, we demonstrate that neural signalling pathways, namely tyraminergic and neuromedin U signalling, regulate entry into CID of the hsf-1 mutant. Overexpression of anti-ageing genes, such as hsf-1, XBP1/xbp-1, FOXO/daf-16, Nrf2/skn-1, and TFEB/hlh-30, also inhibits CID entry of the hsf-1 mutant. Based on these findings, we hypothesise that regulators of the hsf-1 mutant CID may impact longevity, and successfully isolate 16 long-lived mutants among 49 non-CID mutants via genetic screening. Furthermore, we demonstrate that the nonsense mutation of MED23/sur-2 prevents CID entry of the hsf-1(sy441) mutant and extends lifespan. Thus, CID is a powerful model to investigate neural networks involving cold acclimation and to explore new ageing mechanisms.
摘要：
温度是控制许多动物物种的发育和寿命的关键环境线索；然而，对低温适应的潜在机制知之甚少。这里,我们描述了冷诱导滞育（CID），秀丽隐杆线虫低温诱导的另一种滞育。热休克因子1（hsf-1）中的过早终止密码子在9°C触发进入CID，而野生型动物entCID在4°C。此外，野生型和hsf-1(sy441)突变动物都可以存活数周，并在20°C下恢复生长。使用上位性分析，我们证明了神经信号通路，即tyraminine能和神经medinU信号，调节hsf-1突变体进入CID。抗衰老基因的过表达，例如hsf-1、XBP1/xbp-1、FOXO/daf-16、Nrf2/skn-1和TFEB/hlh-30也抑制了hsf-1突变体的sCID进入。基于这些发现,我们假设hsf-1突变CID的调节因子可能会影响寿命，通过遗传筛选，成功分离出49个非CID突变体中的16个长寿命突变体。此外，我们证明MED23/sur-2的无义突变可预防hsf-1（sy441）突变体的CID进入并延长寿命。因此，CID是一个强大的模型，可以研究涉及冷驯化的神经网络并探索新的衰老机制。
