The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans
The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans
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DOI：
10.1016/j.bbrc.2011.02.079
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发表时间：
2011-03-18
影响因子：
3.1
通讯作者：
Swoboda, Peter
中科院分区：
文献类型：
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作者：
Carlos Fierro-Gonzalez, Juan;Gonzalez-Barrios, Maria;Swoboda, Peter
在多种动物模型中，饮食限制（DR）是已知唯一能延长成年动物寿命的环境干预措施。然而，介导DR诱导的抗衰老程序的遗传和细胞事件仍然难以捉摸。在此，我们利用秀丽隐杆线虫提供了第一个体内证据，证明硫氧还蛋白（TRX-1）调节DR诱导的成虫寿命延长。我们发现TRX-1基因的缺失完全抑制了DR的遗传替代物eat-2突变引起的寿命延长。然而，trx-1缺失仅部分抑制胰岛素样受体基因daf-2突变或感觉纤毛基因osm-5突变引起的长寿。在ASJ神经元中，由自身启动子表达的trx-1::GFP翻译融合（Ptrx-1::trx-1::GFP）挽救了trx-1缺失介导的由eat-2突变引起的寿命延长抑制。当从ges-1启动子中表达trx-1::GFP时，没有观察到这种拯救。此外，过表达Ptrx-1::trx-1::GFP在野生型中延长了寿命，而在eat-2突变体中没有延长寿命。trx-1缺失几乎完全抑制了由饮食剥夺（DD）引起的寿命延长，DD是蠕虫的一种非遗传的、基于营养的DR模型。此外，DD上调了衰老成人ASJ神经元中trx-1启动子驱动的GFP报告基因（Ptrx-1::GFP）的表达，但未上调对照组Pgpa-9::GFP（也在ASJ神经元中表达）的表达。我们认为，DR在衰老过程中激活ASJ神经元中的TRX-1，进而触发TRX-1依赖机制，延长蛔虫的成年寿命。(C) 2011爱思唯尔公司版权所有。
Dietary restriction (DR) is the only environmental intervention known to extend adult lifespan in a wide variety of animal models. However, the genetic and cellular events that mediate the anti-aging programs induced by DR remain elusive. Here, we used the nematode Caenorhabditis elegans to provide the first in vivo evidence that a thioredoxin (TRX-1) regulates adult lifespan extension induced by DR. We found that deletion of the gene trx-1 completely suppressed the lifespan extension caused by mutation of eat-2, a genetic surrogate of DR in the worm. However, trx-1 deletion only partially suppressed the long lifespan caused by mutation of the insulin-like receptor gene daf-2 or by mutation of the sensory cilia gene osm-5. A trx-1::GFP translational fusion expressed from its own promoter in ASJ neurons (Ptrx-1::trx-1::GFP) rescued the trx-1 deletion-mediated suppression of the lifespan extension caused by mutation of eat-2. This rescue was not observed when trx-1::GFP was expressed from the ges-1 promoter in the intestine. In addition, overexpression of Ptrx-1::trx-1::GFP extended lifespan in wild type, but not in eat-2 mutants. trx-1 deletion almost completely suppressed the lifespan extension induced by dietary deprivation (DD), a non-genetic, nutrient-based model of DR in the worm. Moreover, DD upregulated the expression of a trx-1 promoter-driven GFP reporter gene (Ptrx-1::GFP) in ASJ neurons of aging adults, but not that of control Pgpa-9::GFP (which is also expressed in ASJ neurons). We propose that DR activates TRX-1 in ASJ neurons during aging, which in turn triggers TRX-1-dependent mechanisms to extend adult lifespan in the worm. (C) 2011 Elsevier Inc. All rights reserved.