Comparative analysis of gene expression and regulation of replicative aging associated genes in S. cerevisiae

Abstract

Aging is a multi-factorial and complex phenomenon. Saccharomyces cerevisiae is developed as a model of aging and has been widely studied in order to understand the mechanism of lifespan regulation. A large number of high-throughput studies were conducted to identify the genes which modulate lifespan. These studies provide the list of genes that regulates the lifespan in yeast; however the regulation of these aging associated genes had not been fully understood. In this study, we have shown that deletion of the genes which increase the replicative lifespan (RLS) of yeast show discrete expression patterns when compared with the genes that, on deletion, cause a decrease in lifespan. Expression of longlived (LL) genes decreases as the cell progresses from mid log to stationary phase, whereas expression of shortlived (SL) genes remains unchanged. This distinct expression of LL and SL gene-sets suggests their differential gene regulation. Further analysis of transcriptional regulation by transcription factors and epigenetic regulators (acetylation and methylation) suggests that this differential expression of the two gene-sets is due to their differential epigenetic regulations, rather than regulation by transcription factors. These results accentuate the importance of epigenetic modifications in aging. We deduce that future focused studies on epigenetic modification regulation will help lead to a better understanding of the aging process.