Regulation of Longevity and Stress Resistance by Sch9 in Yeast
Abstract
The protein kinase Akt/protein kinase B (PKB) is implicated in insulin signaling in mammals and functions in a pathway that regulates longevity and stress resistance in Caenorhabditis elegans. We screened for long-lived mutants in nondividing yeastSaccharomyces cerevisiae and identified mutations in adenylate cyclase and SCH9, which is homologous to Akt/PKB, that increase resistance to oxidants and extend life-span by up to threefold. Stress-resistance transcription factors Msn2/Msn4 and protein kinase Rim15 were required for this life-span extension. These results indicate that longevity is associated with increased investment in maintenance and show that highly conserved genes play similar roles in life-span regulation in S. cerevisiae and higher eukaryotes.
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Supported by NIH grants AG 08761-10 (J. W. Vaupel, V.D.L.) and AG09793 (T. H. McNeill), by an American Federation of Aging Research grant (V.D.L.), and by a John Douglas French Alzheimer's Foundation grant (V.D.L.). We thank J. Martin and G. Fenimore for their generous donations, C. Finch and E. Gralla for careful reading of the manuscript, D. Thiele, J. Hirsh, M. Carlson, S. Garrett, A. Mitchell, and J. Field for providing yeast plasmids, J. Vaupel for generously allowing the use of Max Planck Institute facilities and instruments, and M. Wei for performing data analysis.
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Science
Volume 292 | Issue 5515
13 April 2001
13 April 2001
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Received: 1 February 2001
Accepted: 15 March 2001
Published in print: 13 April 2001
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