High osmolarity extends life span in Saccharomyces cerevisiae by a mechanism related to calorie restriction.
Calorie restriction (CR) extends life span in many different organisms, including mammals. We describe here a novel pathway that extends the life span of Saccharomyces cerevisiae mother cells but does not involve a reduction in caloric content of the media, i.e., there is growth of yeast cells in the presence of a high concentration of external osmolytes. Like CR, this longevity-promoting response to high osmolarity requires SIR2, suggesting a common mechanism of life span regulation. Genetic and microarray analysis indicates that high osmolarity extends the life span by activating Hog1p, leading to an increase in the biosynthesis of glycerol from glycolytic intermediates. This metabolic shift likely increases NAD levels, thereby activating Sir2p and promoting longevity.
Kaeberlein
Matt
M
Longenity, Inc., Waltham, Massachusetts 02451, USA. matt@longenity.com
Andalis
Alex A
AA
Fink
Gerald R
GR
Guarente
Leonard
L
D000818:Animals; D031204:Caloric Restriction; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D005990:Glycerol / Q000737:chemistry / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D008017:Life Expectancy; D015394:Molecular Structure; D009243:NAD / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009994:Osmolar Concentration; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D013012:Sorbitol / Q000737:chemistry / Q000378:metabolism; D014993:Xylitol / Q000737:chemistry / Q000378:metabolism
D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D009243:NAD; D013012:Sorbitol; D009713:Nucleotidyltransferases; C026917:mannose 1-phosphate guanylyltransferase; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D005947:Glucose; D005990:Glycerol; D014993:Xylitol