Lesur Isabelle, Campbell Judith L
Braun Laboratories 147-75, California Institute of Technology, Pasadena, California 91125, USA.
Mol Biol Cell. 2004 Mar;15(3):1297-312. doi: 10.1091/mbc.e03-10-0742. Epub 2004 Jan 12.
To help define the pathologies associated with yeast cells as they age, we analyzed the transcriptome of young and old cells isolated by elutriation, which allows isolation of biochemical quantities of old cells much further advanced in their life span than old cells prepared by the biotin-streptavidin method. Both 18-generation-old wild-type yeast and 8-generation-old cells from a prematurely aging mutant (dna2-1), with a defect in DNA replication, were evaluated. Genes involved in gluconeogenesis, the glyoxylate cycle, lipid metabolism, and glycogen production are induced in old cells, signifying a shift toward energy storage. We observed a much more extensive generalized stress response known as the environmental stress response (ESR), than observed previously in biotin-streptavidin-isolated cells, perhaps because the elutriated cells were further advanced in their life span. In addition, there was induction of DNA repair genes that fall in the so-called DNA damage "signature" set. In the dna2-1 mutant, energy production genes were also induced. The response in the dna2-1 strain is similar to the telomerase delete response, genes whose expression changes during cellular senescence in telomerase-deficient cells. We propose that these results suggest, albeit indirectly, that old cells are responding to genome instability.
为了帮助确定酵母细胞衰老过程中相关的病理变化，我们分析了通过淘析法分离的年轻细胞和衰老细胞的转录组，这种方法能够分离出比通过生物素-链霉亲和素法制备的衰老细胞在寿命上更老的生物化学量的衰老细胞。我们评估了18代的野生型酵母细胞以及来自早衰突变体（dna2-1）的8代细胞，该突变体在DNA复制方面存在缺陷。参与糖异生、乙醛酸循环、脂质代谢和糖原生成的基因在衰老细胞中被诱导表达，这表明细胞向能量储存方向转变。我们观察到一种比之前在生物素-链霉亲和素分离的细胞中更广泛的普遍应激反应，即环境应激反应（ESR），这可能是因为淘析法分离的细胞在寿命上更老。此外，属于所谓DNA损伤“特征”集的DNA修复基因也被诱导表达。在dna2-1突变体中，能量产生相关基因也被诱导表达。dna2-1菌株中的反应类似于端粒酶缺失反应，即在端粒酶缺陷细胞的细胞衰老过程中表达发生变化的基因。我们认为，尽管是间接的，但这些结果表明衰老细胞正在对基因组不稳定做出反应。
