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Published March 2004 | Published
Journal Article Open

The Transcriptome of Prematurely Aging Yeast Cells Is Similar to That of Telomerase-deficient Cells


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.

Additional Information

Copyright © 2004 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0). Submitted October 16, 2003; Revised November 30, 2003; Accepted November 30, 2003. Originally published as MBC in Press, 10.1091/mbc.E03-10-0742 on January 12, 2004 We thank Shelley Diamond for assistance with the elutriation centrifuge and flow cytometry. We thank Laura Hoopes for stimulating discussions throughout the course of this work and for comments on the manuscript. We are also very grateful for the suggestions of Sagar Damle. Microarray analyses were performed in the Gene Expression Facility of the Biology Division at Caltech. We thank Barbara Wold for advice and the use of a server. Isabelle Lesur is a participant in the Initiative in Computational Molecular Biology, which is funded, in part, by an award from the Burroughs Wellcome Fund Interfaces program. This work was supported by national Institutes of Health grant GM-25508.

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