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Vol. 15, Issue 3, 1297-1312, March 2004
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* Braun Laboratories 147-75, California Institute of Technology, Pasadena, California 91125;
Laboratoire Bordelais de Recherche en Informatique, Universite Bordeaux I, Talence 33405, France
Submitted October 16, 2003;
Revised November 30, 2003;
Accepted November 30, 2003
Monitoring Editor: David Botstein
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.
Abbreviations used: ESR, environmental stress response; HEO, high external osmolarity; LOH, loss of heterozygosity; MMS, methyl methanesulfonate; TCA, tricarboxylic-acid pathway; TDR, telomerase-deficient response; TDS, telomerase-deficient signature.
Corresponding author. E-mail address: jcampbel{at}cco.caltech.edu.
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