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.