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A more recent version of this article appeared on March 1, 2004
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Submitted on October 16, 2003
Revised on November 30, 2003
Accepted on November 30, 2003
1 Braun Laboratories 147-75, California Institute of Technology, Pasadena, CA 91125, Laboratoire Bordelais de Recherche en Informatique, Universite Bordeaux I, 351 cours de la Liberation, Talence, France, 33405
* Corresponding author. E-mail address: jcampbel{at}cco.caltech.edu.
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 eight 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 ESR, the environmental stress response, 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 TDR (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.
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