Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans.
Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans.
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DOI：
10.1111/j.1474-9726.2009.00459.x
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发表时间：
2009-04
期刊：
影响因子：
7.8
通讯作者：
Brunet A
中科院分区：
文献类型：
--
作者：
Greer EL;Brunet A
饮食限制（DR）具有延长寿命和健康的显着能力。已经在从酵母到哺乳动物的物种中描述了多种DR方案。然而，不同的DR方案是否通过普遍的、不同的或重叠的途径延长寿命仍然是一个悬而未决的问题。在这里，我们研究介导不同的DR方案在秀丽隐杆线虫长寿的遗传途径。我们以前已经表明，低能量感应AMP激活的蛋白激酶AMPK/aak-2和叉头转录因子FoxO/daf-16是必要的长寿诱导的DR方案，我们开发的（sDR）。在这里，我们发现AMPK和FoxO是另一种DR方案诱导的寿命所必需的，但对于两种不同DR方法诱导的寿命延长是不必要的。有趣的是，AMPK也是必要的寿命延长引起的白藜芦醇，天然多酚，模仿DR的某些方面。相反，我们测试，如果基因先前报道的介导寿命的各种DR方法是必要的sDR诱导的寿命。虽然参与泛醌生物合成的基因sir-1也是sDR诱导的寿命延长所必需的，但我们发现其他四个基因（sir-2.1，FoxA/pha-4，skn-1和hsf-1）都是sDR诱导的寿命延长所必需的。与不同的DR方法通过大多数独立的遗传机制延长寿命的观察结果一致，我们发现两种不同的DR方案对寿命的影响是累加的。了解不同DR方案延长寿命的遗传网络对于利用DR对寿命和健康的全部益处具有重要意义。
Dietary restriction (DR) has the remarkable ability to extend lifespan and healthspan. A variety of DR regimens have been described in species ranging from yeast to mammals. However, whether different DR regimens extend lifespan via universal, distinct, or overlapping pathways is still an open question. Here we examine the genetic pathways that mediate longevity by different DR regimens in Caenorhabditis elegans. We have previously shown that the low-energy sensing AMP-activated protein kinase AMPK/aak-2 and the Forkhead transcription factor FoxO/daf-16 are necessary for longevity induced by a DR regimen that we developed (sDR). Here we find that AMPK and FoxO are necessary for longevity induced by another DR regimen, but are dispensable for the lifespan extension induced by two different DR methods. Intriguingly, AMPK is also necessary for the lifespan extension elicited by resveratrol, a natural polyphenol that mimics some aspects of DR. Conversely, we test if genes previously reported to mediate longevity by a variety of DR methods are necessary for sDR-induced longevity. Although clk-1, a gene involved in ubiquinone biosynthesis, is also required for sDR-induced lifespan extension, we find that four other genes (sir-2.1, FoxA/pha-4, skn-1, and hsf-1) are all dispensable for longevity induced by sDR. Consistent with the observation that different DR methods extend lifespan by mostly independent genetic mechanisms, we find that the effects on lifespan of two different DR regimens are additive. Understanding the genetic network by which different DR regimens extend lifespan has important implications for harnessing the full benefits of DR on lifespan and healthspan.
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影响因子：
4
作者：
Greer, Eric L.;Brunet, Anne
通讯作者：
Brunet, Anne
影响因子：
7.8
作者：
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通讯作者：
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3.9
作者：
Anisimov, VN;Berstein, LM;Franceschi, C
通讯作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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