Pathways Change in Expression During Replicative Aging in Saccharomyces cerevisiae

Abstract

Yeast replicative aging is a process resembling replicative aging in mammalian cells. During aging, wild-type haploid yeast cells enlarge, become sterile, and undergo nucleolar enlargement and fragmentation; we sought gene expression changes during the time of these phenotypic changes. Gene expression studied via microarrays and quantitative real-time reverse-transcription polymerase chain reaction (qPCR) has shown reproducible, statistically significant changes in messenger RNA (mRNA) of genes at 12 and 18-20 generations. Our findings support previously described changes towards aerobic metabolism, decreased ribosome gene expression, and a partial environmental stress response. Our findings include a pseudostationary phase, downregulation of methylation-related metabolism, increased nucleotide excision repair-related mRNA, and a strong upregulation of many of the regulatory subunits of protein phosphatase I (Glc7). These findings are correlated with aging changes in higher organisms as well as with the known involvement of protein phosphorylation states during yeast aging.

Changes in Transcription and Metabolism During the Early Stage of Replicative Cellular Senescence in Budding Yeast

“…1). Transcriptome analysis of 18 -20-generation-old wild-type cells was reported previously and showed that cellular aging is associated with a shift toward gluconeogenesis and energy storage and a response to genome instability (7,15). The transcripts at this age, however, might include information from dead cells or exclude information from lysed cells.…”

“…In all cases, a shift from glycolysis toward gluconeogenesis and energy storage (glyoxylate cycle, lipid metabolism, and glycogen production) was observed in old cells. In addition, the expression of ribosome genes and genes involved in protein synthesis, folding, and degradation all decreased (14,15). Besides changes in metabolic gene expression, environmental stress response genes were induced in aged cells (7), although oxidative stress gene expression did not change (14).…”

“…Several transcriptome analyses comparing old cells with young cells have shown pathway changes in expression during replicative aging (7,(13)(14)(15). In all cases, a shift from glycolysis toward gluconeogenesis and energy storage (glyoxylate cycle, lipid metabolism, and glycogen production) was observed in old cells.…”

“…Besides changes in metabolic gene expression, environmental stress response genes were induced in aged cells (7), although oxidative stress gene expression did not change (14). Genes involved in DNA damage repair such as homologous recombination and nucleotide excision repair were also induced in old cells (7,15). These transcriptome studies examined 18 -20-generation-old yeast cells (i.e.…”

“…These transcriptome studies examined 18 -20-generation-old yeast cells (i.e. approaching the end of an average lifespan) prepared by using biotinstreptavidin technology or a centrifugal elutriator (7,14,15). About half of the population of cells is dead by the average generation time, so the transcriptome data from the 18th to 20th generation cells may contain information from dead cells.…”