Sound silencing: the Sir2 protein and cellular senescence

The model organism Saccharomyces cerevisiae is providing new insights into the molecular and cellular changes that are related to aging. The yeast pro tein Sir2p (Silent Information Regulator 2) is a histone deacetylase involv ed in transcriptional silencing and the control of genomic stability. Recen t results have led to the identification of Sir2p as a crucial determinant of yeast life span. Dosage, intracellular localization, and activity of Sir 2p all have important effects on yeast longevity, For instance, calorie res triction apparently increases yeast life span by increasing Sir2p activity, Since Sir2p-related proteins have been identified in many prokaryotic and eukaryotic organisms, the fundamental principles derived from the studies i n yeast may prove valuable in directing our future research toward an under standing of the mechanisms of aging in higher eukaryotes, (C) 2001 John Wil ey & Sons, Inc.