The rRNA gene, which consists of tandem repetitive arrays (ribosomal DNA [rDNA] repeat), is one of the most unstable regions in the genome. The rDNA repeat in the budding yeast Saccharomyces cerevisiae is known to become unstable as the cell ages. However, it is unclear how the rDNA repeat changes in aging mammalian cells. Using quantitative single-cell analyses, we identified age-dependent alterations in rDNA copy number and levels of methylation in mice. The degree of methylation and copy number of rDNA from bone marrow cells of 2-year-old mice were increased by comparison to levels in 4-week-old mice in two mouse strains, BALB/cA and C57BL/6. Moreover, the level of pre-rRNA transcripts was reduced in older BALB/cA mice. We also identified many sequence variations in the rDNA. Among them, three mutations were unique to old mice, and two of them were found in the conserved region in budding yeast. We established yeast strains with the old-mouse-specific mutations and found that they shortened the life span of the cells. Our findings suggest that rDNA is also fragile in mammalian cells and that alterations within this region have a profound effect on cellular function.

中文翻译：

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小鼠中年龄依赖性核糖体DNA变异。

由串联重复阵列（核糖体DNA [rDNA]重复序列）组成的rRNA基因是基因组中最不稳定的区域之一。rDNA在萌芽的酿酒酵母中重复随着细胞的衰老，它变得不稳定。然而，尚不清楚rDNA在衰老的哺乳动物细胞中如何重复变化。使用定量单细胞分析，我们确定了小鼠中rDNA拷贝数和甲基化水平的年龄依赖性变化。通过与两种小鼠品系BALB / cA和C57BL / 6中4周龄小鼠的水平比较，可以提高2年龄小鼠骨髓细胞的rDNA甲基化程度和拷贝数。此外，在较年长的BALB / cA小鼠中，rRNA前转录物的水平降低了。我们还鉴定了rDNA中的许多序列变异。其中，三个突变是老年小鼠特有的，其中两个在发芽酵母的保守区中发现。我们建立了具有旧小鼠特异性突变的酵母菌株，发现它们缩短了细胞的寿命。