Calorie restriction reduces rDNA recombination independently of rDNA silencing.
Calorie restriction reduces rDNA recombination independently of rDNA silencing.
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DOI：
10.1111/j.1474-9726.2009.00514.x
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发表时间：
2009-12
期刊：
影响因子：
7.8
通讯作者：
Morgan A
中科院分区：
文献类型：
--
作者：
Riesen M;Morgan A
热量限制（CR）延长酵母，蠕虫，苍蝇和哺乳动物的寿命，表明它通过保守的机制发挥作用。在酵母中，通过CR激活NAD依赖性组蛋白脱乙酰酶Sir2被认为增加核糖体DNA的沉默，从而减少重组诱导的染色体外rDNA环的产生，从而增加复制寿命。尽管染色体外rDNA环的积累是酵母老化所特有的，但认为Sirtuin激活代表了一种保守的长寿机制，通过该机制，CR的有益作用在各种物种中被介导。我们在这里表明，与标准（2%葡萄糖）培养基相比，在0.05或0.5%葡萄糖（分别为重度和中度CR）上生长的酵母不会增加亚端粒或rDNA位点的沉默。此外，rDNA沉默在CR的hxk2Δ、sch9Δ和tor1Δ遗传模拟物中不受影响，但被FOB 1缺失抑制。所有这些干预措施都延长了多种酵母背景下的寿命，揭示了rDNA沉默与寿命之间的相关性较差。相反，CR和FOB1，HXK2，SCH9和TOR1基因的缺失，都显着减少rDNA重组。因此，这种抑制rDNA重组的沉默独立机制可能有助于CR介导的寿命延长。
Calorie restriction (CR) extends lifespan in yeast, worms, flies and mammals, suggesting that it acts via a conserved mechanism. In yeast, activation of the NAD-dependent histone deacetylase, Sir2, by CR is thought to increase silencing at the ribosomal DNA, thereby reducing the recombination-induced generation of extrachromosomal rDNA circles, hence increasing replicative lifespan. Although accumulation of extrachromosomal rDNA circles is specific to yeast aging, it is thought that Sirtuin activation represents a conserved longevity mechanism through which the beneficial effects of CR are mediated in various species. We show here that growing yeast on 0.05 or 0.5% glucose (severe and moderate CR, respectively) does not increase silencing at either sub-telomeric or rDNA loci compared with standard (2% glucose) media. Furthermore, rDNA silencing was unaffected in the hxk2Δ, sch9Δ and tor1Δ genetic mimics of CR, but inhibited by FOB1 deletion. All these interventions extend lifespan in multiple yeast backgrounds, revealing a poor correlation between rDNA silencing and longevity. In contrast, CR and deletion of the FOB1, HXK2, SCH9 and TOR1 genes, all significantly reduced rDNA recombination. This silencing-independent mechanism for suppressing rDNA recombination may therefore contribute to CR-mediated lifespan extension.
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