title: Nutritional Control of Chronological Aging and Heterochromatin inSaccharomyces cerevisiae.
abstract: Calorie restriction extends life span in organisms as diverse as yeast and mammals through incompletely understood mechanisms.The role of NAD+-dependent deacetylases known as Sirtuins in this process, particularly in the yeastSaccharomyces cerevisiae, is controversial. We measured chronological life span of wild-type andsir2Δ strains over a higher glucose range than typically used for studying yeast calorie restriction.sir2Δ extended life span in high glucose complete minimal medium and had little effect in low glucose medium, revealing a partial role for Sir2 in the calorie-restriction response under these conditions. Experiments performed on cells grown in rich medium with a newly developed genetic strategy revealed thatsir2Δ shortened life span in low glucose while having little effect in high glucose, again revealing a partial role for Sir2 In complete minimal media, Sir2 shortened life span as glucose levels increased; whereas in rich media, Sir2 extended life span as glucose levels decreased. Using a genetic strategy to measure the strength of gene silencing atHML, we determined increasing glucose stabilized Sir2-based silencing during growth on complete minimal media. Conversely, increasing glucose destabilized Sir-based silencing during growth on rich media, specifically during late cell divisions. In rich medium, silencing was far less stable in high glucose than in low glucose during stationary phase. Therefore, Sir2 was involved in a response to nutrient cues including glucose that regulates chronological aging, possibly through Sir2-dependent modification of chromatin or deacetylation of a nonhistone protein.
authors.affiliation: Department of Molecular and Cell Biology, University of California at Berkeley, California 94720.
authors.forename: David F
authors.initials: DF
authors.lastname: McCleary
authors.affiliation: Department of Molecular and Cell Biology, University of California at Berkeley, California 94720 jrine@berkeley.edu.
authors.forename: Jasper
authors.initials: J
authors.lastname: Rine
mesh_terms: D002453:Cell Cycle; D005947:Glucose / Q000172:deficiency*; D006570:Heterochromatin / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D006570:Heterochromatin; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D005947:Glucose
keywords: Sir2; aging; gene silencing; heterochromatin; nutrition