Longevity regulation in Saccharomyces cerevisiae: linking metabolism, genome stability, and heterochromatin.
When it was first proposed that the budding yeast Saccharomyces cerevisiae might serve as a model for human aging in 1959, the suggestion was met with considerable skepticism. Although yeast had proved a valuable model for understanding basic cellular processes in humans, it was difficult to accept that such a simple unicellular organism could provide information about human aging, one of the most complex of biological phenomena. While it is true that causes of aging are likely to be multifarious, there is a growing realization that all eukaryotes possess surprisingly conserved longevity pathways that govern the pace of aging. This realization has come, in part, from studies of S. cerevisiae, which has emerged as a highly informative and respected model for the study of life span regulation. Genomic instability has been identified as a major cause of aging, and over a dozen longevity genes have now been identified that suppress it. Here we present the key discoveries in the yeast-aging field, regarding both the replicative and chronological measures of life span in this organism. We discuss the implications of these findings not only for mammalian longevity but also for other key aspects of cell biology, including cell survival, the relationship between chromatin structure and genome stability, and the effect of internal and external environments on cellular defense pathways. We focus on the regulation of replicative life span, since recent findings have shed considerable light on the mechanisms controlling this process. We also present the specific methods used to study aging and longevity regulation in S. cerevisiae.
Bitterman
Kevin J
KJ
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Medvedik
Oliver
O
Sinclair
David A
DA
D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D006570:Heterochromatin / Q000235:genetics / Q000502:physiology*; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008958:Models, Molecular; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000502:physiology
D006570:Heterochromatin; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases