Riesen M and Morgan A (2009) Calorie restriction reduces rDNA recombination independently of rDNA silencing. Aging Cell 8(6):624-632
Abstract: SUMMARY 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 ageing, 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 to standard (2% glucose) media. Furthermore, rDNA silencing was unaffected in the hxk2Delta, sch9Delta and tor1Delta 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.
|Status: Published||Type: Journal Article||PubMed ID: 19732046|
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