Effect of replicative age on transcriptional silencing near telomeres in Saccharomyces cerevisiae.

Individual yeasts have a finite replicative life span in similarity to normal human fibroblasts. Telomere loss is a hallmark of replicative senescence in normal human fibroblasts and has been proposed to play a role in cellular senescence, perhaps by affecting subtelomeric genes. While telomere loss does not occur with replicative age in yeast, subtelomeric genes are subject to transcriptional silencing. It is possible that components of the silencing machinery other than telomeres change with replicative age and that these changes then lead to alterations in gene expression that contribute to aging. In an initial test of this possibility, we have examined the silencing of the URA3 gene at two different telomeres as a function of yeast replicative age. Silencing declined rapidly and significantly at one telomere consistent with the involvement of silencing in aging, but it remained in comparison nearly constant at the other. These changes in silencing raise the possibility that the transcriptional status of genes in the subtelomeric region may be important for the senescence of both dividing cells and postmitotic cells, in which telomeres remain constant in length.