Lifespan extension by suppression of autophagy genes in Caenorhabditis elegans
Lifespan extension by suppression of autophagy genes in Caenorhabditis elegans
复制标题
DOI：
10.1111/j.1365-2443.2009.01306.x
复制
发表时间：
2009-06-01
期刊：
影响因子：
2.1
通讯作者：
Nishida, Eisuke
中科院分区：
文献类型：
--
作者：
Hashimoto, Yasufumi;Ookuma, Sadatsugu;Nishida, Eisuke
寿命受到环境和遗传因素的复杂组合的调节。自噬是一种大分子和细胞器的整体降解系统，在各种生物事件中发挥着重要作用。在秀丽隐杆线虫中，一些自噬基因已被证明具有促进寿命的作用，但许多其他自噬基因尚未被研究其在寿命调节中的作用。在这里，我们系统地研究了RNAi抑制14个自噬基因对寿命的影响。虽然野生型蠕虫中自噬基因的母体RNAi倾向于缩短寿命，但胰岛素/IGF-1受体daf-2突变体中七个自噬基因中的每一个的母体RNAi都延长了寿命。值得注意的是，来自年轻成年人（即发育后）的unc-51/atg-1、bec-1/atg-6或atg-9的RNAi延长了野生型动物和daf-2突变体的寿命，尽管一个或两个基因的RNAi缩短了寿命。此外，我们的分析表明，发育后由unc-51、bec-1或atg-9的RNAi诱导的寿命延长，不需要转录因子daf-16、NAD（+）依赖性蛋白脱乙酰酶sir-2.1或与线粒体功能相关的基因。总的来说，我们的研究结果表明，自噬可能并不总是有益于长寿，但也可能起到限制C。优雅的
Lifespan is regulated by a complex combination of environmental and genetic factors. Autophagy, which is a bulk degradation system of macromolecules and organelles, has an important role in various biological events. In Caenorhabditis elegans, several autophagy genes have been shown to have a role in promoting longevity, but many other autophagy genes have not been examined for their role in the lifespan regulation. Here we have systematically examined the effect of RNAi suppression of 14 autophagy genes on lifespan. While maternal RNAi of autophagy genes in wild-type worms tended to reduce lifespan, maternal RNAi of each of seven autophagy genes in the insulin/IGF-1 receptor daf-2 mutants extended lifespan. Remarkably, RNAi of unc-51/atg-1, bec-1/atg-6 or atg-9, from young adult, i.e. after development, extended lifespan in both wild-type animals and daf-2 mutants, although RNAi of one or two genes shortened it. Moreover, our analysis suggests that the lifespan extension, which is induced by RNAi of unc-51, bec-1 or atg-9 after development, does not require the transcription factor daf-16, the NAD(+)-dependent protein deacetylase sir-2.1 or the genes related to mitochondrial functions. Collectively, our results suggest that autophagy may not always be beneficial to longevity, but may also function to restrict lifespan in C. elegans.