title: A mathematical model of ageing in yeast.
abstract: Budding yeast, Saccharomyces cerevisiae, is commonly used as a system to study cellular ageing. Yeast mother cells are capable of only a limited number of divisions before they undergo senescence, whereas newly formed daughters usually have their replicative age "reset" to zero. Accumulation of extrachromosomal ribosomal DNA circles (ERCs) appears to be an important contributor to ageing in yeast, and we describe a mathematical model that we developed to examine this process. We show that an age-related accumulation of ERCs readily explains the observed features of yeast ageing but that in order to match the experimental survival curves quantitatively, it is necessary that the probability of ERC formation increases with the age of the cell. This implies that some other mechanism(s), in addition to ERC accumulation, must underlie yeast ageing. We also demonstrate that the model can be used to gain insight into how an extra copy of the Sir2 gene might extend lifespan and we show how the model makes novel, testable predictions about patterns of age-specific mortality in yeast populations.
authors.affiliation: Henry Wellcome Laboratory for Biogerontology Research, SCMS-Gerontology, University of Newcastle, Newcastle General Hospital, Newcastle upon Tyne, NE4 6BE, UK. c.gillespie@ncl.ac.uk
authors.forename: Colin S
authors.initials: CS
authors.lastname: Gillespie
authors.forename: Carole J
authors.initials: CJ
authors.lastname: Proctor
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Boys
authors.forename: Daryl P
authors.initials: DP
authors.lastname: Shanley
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Wilkinson
authors.forename: Thomas B L
authors.initials: TB
authors.lastname: Kirkwood
mesh_terms: D000375:Aging / Q000235:genetics; D002455:Cell Division; D004270:DNA, Circular; D004275:DNA, Ribosomal; D020440:Gene Duplication; D006655:Histone Deacetylases / Q000235:genetics; D008957:Models, Genetic; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics
chemical_list: D004270:DNA, Circular; D004275:DNA, Ribosomal; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases