Paradigms and pitfalls of yeast longevity research

Over the past 10 years, considerable progress has been made in the yeast aging field. Multiple lines of evidence indicate that a cause of yeast aging stems from the inherent instability of repeated ribosomal DNA (rDNA). Over 16 yeast longevity genes have now been identified and the majority of these have been found to affect rDNA silencing or stability. Environmental conditions such as calorie restriction have been shown to modulate this mode of aging via Sir2, an NAD-dependent histone deacetylase (HDAC) that binds at the rDNA locus. Although this mechanism of aging appears to be yeast-specific, the longevity function of Sir2 is conserved in at least one multicellular organism, Caenorhabditis elegans (C. elegans). These findings are consistent with the idea that aging is a by-product of natural selection but longevity regulation is a highly adaptive trait. Characterizing this and other mechanisms of yeast aging should help identify additional components of longevity pathways in higher organisms.