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Molecular and Cellular Biology, November 2002, p. 8056-8066, Vol. 22, No. 22
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.22.8056-8066.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

High Osmolarity Extends Life Span in Saccharomyces cerevisiae by a Mechanism Related to Calorie Restriction

Matt Kaeberlein,1* Alex A. Andalis,2 Gerald R. Fink,2 and Leonard Guarente3

Longenity, Inc., Waltham, Massachusetts 02451,1 Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142,2 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 021393

Received 3 June 2002/ Returned for modification 10 July 2002/ Accepted 15 August 2002

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.

* Corresponding author. Mailing address: Longenity, Inc., Waltham, MA 02451. Phone: (781) 209-0249. Fax: (781) 209-0175. E-mail: matt{at}longenity.com.

Molecular and Cellular Biology, November 2002, p. 8056-8066, Vol. 22, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.22.8056-8066.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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