The budding yeast Saccharomyces cerevisiae has a finite life span, limited by the number of generations the cell can undergo. Yeast cells display a variety of changes as they age. In order to determine whether age-associated changes occur in the prevalence of specific mRNAs, a differential hybridization screen has been used to identify yeast genes that are preferentially expressed in either young or in old cells. In this screen, a yeast genomic DNA library was probed with cDNA prepared to the poly(A)+ mRNA of young and old cells. Six clones representing distinct genes that showed differential patterns of expression throughout the life span were isolated, as determined by genomic blot and RNA dot blot analyses. On the basis of their expression patterns five of the genes were classified as young- and one as old-specific. These genes were all derived from the nuclear genome. Analysis of the expression during the cell cycle of two of these genes, one young cell-specific and the other old-cell-specific, revealed that it was not growth state-dependent. These results suggest that aging in yeast is accompanied by defined alterations in the levels of certain gene transcripts.