Knockdown of Indy/CeNac2 extends Caenorhabditis elegans life span by inducing AMPK/aak-2
Knockdown of Indy/CeNac2 extends Caenorhabditis elegans life span by inducing AMPK/aak-2
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DOI：
10.18632/aging.100791
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发表时间：
2015-08-01
期刊：
影响因子：
5.2
通讯作者：
Birkenfeld, Andreas L.
中科院分区：
文献类型：
--
作者：
Schwarz, Franziska;Karadeniz, Zehra;Birkenfeld, Andreas L.
在低等生物体中，降低Indy（“I'm Not Dead，Yet”的首字母缩写）基因的表达可促进长寿，并导致类似于热量限制的各个方面的表型。In C.对于线虫，关于寿命延长的现有数据是有争议的。因此，本研究的目的是确定C。目的：探讨CeNAC 2在线虫寿命调控中的作用及其可能的分子机制。针对Indy/CeNAC 2的siRNA用于降低Indy/CeNAC 2的表达。在四个独立的实验中评估了平均寿命，以及全身脂肪含量和AMPK活化。此外，Indy/CeNAC 2基因敲除对C.研究了具有AMPK失活变体（TG 38）的线虫。与对照siRNA处理的C相比，Indy/CeNAC 2的敲除使寿命延长了22 +/-3%。elegans，以及全身脂肪含量降低了约50%。Indy/CeNAC 2减少也增加了细胞内能量传感器AMPK/aak 2的活化。在没有功能性AMPK/aak 2的蠕虫中，当Indy/CeNAC 2减少时，寿命并没有延长。用脱氧葡萄糖抑制糖酵解（一种已知可增加AMPK/aak 2活性和寿命的干预措施），当Indy/CeNAC 2被敲除时，并不能促进寿命。总之，这些数据表明，减少Indy/CeNAC 2的表达增加了C.一种至少部分由AMPK/aak 2介导的作用。
Reducing the expression of the Indy (Acronym for 'I'm Not Dead, Yet') gene in lower organisms promotes longevity and leads to a phenotype that resembles various aspects of caloric restriction. In C. elegans, the available data on life span extension is controversial. Therefore, the aim of this study was to determine the role of the C. elegans INDY homolog CeNAC2 in life span regulation and to delineate possible molecular mechanisms. siRNA against Indy/CeNAC2 was used to reduce expression of Indy/CeNAC2. Mean life span was assessed in four independent experiments, as well as whole body fat content and AMPK activation. Moreover, the effect of Indy/CeNAC2 knockdown in C. elegans with inactivating variants of AMPK (TG38) was studied. Knockdown of Indy/CeNAC2 increased life span by 22 +/- 3 % compared to control siRNA treated C. elegans, together with a decrease in whole body fat content by similar to 50%. Indy/CeNAC2 reduction also increased the activation of the intracellular energy sensor AMPK/aak2. In worms without functional AMPK/aak2, life span was not extended when Indy/CeNAC2 was reduced. Inhibition of glycolysis with deoxyglucose, an intervention known to increase AMPK/aak2 activity and life span, did not promote longevity when Indy/CeNAC2 was knocked down. Together, these data indicate that reducing the expression of Indy/CeNAC2 increases life span in C. elegans, an effect mediated at least in part by AMPK/aak2.