EFFECT OF REPLICATIVE AGE ON TRANSCRIPTIONAL SILENCING NEAR TELOMERESIN 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, sub telomeric genes are subject to transcriptional silencing. It is possib le that components of the silencing machinery other than telomeres cha nge with replicative age and that these changes then lead to alteratio ns in gene expression that contribute to aging. In an initial test of this possibility, we have examined the silencing of the URA3 gene at t wo different telomeres as a function of yeast replicative age. Silenci ng declined rapidly and significantly at one telomere consistent with the involvement of silencing in aging, but it remained in comparison n early constant at the other. These changes in silencing raise the poss ibility that the transcriptional status of genes in the subtelomeric r egion may be important for the senescence of both dividing cells and p ostmitotic cells, in which telomeres remain constant in length. (C) 19 96 Academic Press, Inc.