Sir2-independent life span extension by calorie restriction in yeast.
Calorie restriction slows aging and increases life span in many organisms. In yeast, a mechanistic explanation has been proposed whereby calorie restriction slows aging by activating Sir2. Here we report the identification of a Sir2-independent pathway responsible for a majority of the longevity benefit associated with calorie restriction. Deletion of FOB1 and overexpression of SIR2 have been previously found to increase life span by reducing the levels of toxic rDNA circles in aged mother cells. We find that combining calorie restriction with either of these genetic interventions dramatically enhances longevity, resulting in the longest-lived yeast strain reported thus far. Further, calorie restriction results in a greater life span extension in cells lacking both Sir2 and Fob1 than in cells where Sir2 is present. These findings indicate that Sir2 and calorie restriction act in parallel pathways to promote longevity in yeast and, perhaps, higher eukaryotes.
Kaeberlein
Matt
M
Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
Kirkland
Kathryn T
KT
Fields
Stanley
S
Kennedy
Brian K
BK
D031204:Caloric Restriction; D003470:Culture Media / Q000378:metabolism; D004275:DNA, Ribosomal / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D030541:Databases, Genetic; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005821:Genetic Techniques; D006655:Histone Deacetylases / Q000235:genetics* / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology*; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics* / Q000502:physiology*; D013045:Species Specificity; D013997:Time Factors
D003470:Culture Media; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; C105579:FOB1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases