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 yeast Saccharomyces 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenylyl Cyclases / genetics
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Adenylyl Cyclases / metabolism
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Amino Acid Sequence
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Animals
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / physiology
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Culture Media
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Cyclic AMP-Dependent Protein Kinases / metabolism
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DNA Transposable Elements
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Drosophila / genetics
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Drosophila / physiology
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Drug Resistance, Microbial
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Gene Deletion
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Hot Temperature
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Longevity
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Molecular Sequence Data
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Mutagenesis, Insertional
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Oxidants / pharmacology
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Paraquat / pharmacology
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Phenotype
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Protein Kinases / chemistry
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Protein Kinases / genetics
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Protein Kinases / metabolism*
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Saccharomyces cerevisiae / enzymology
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / physiology*
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Saccharomyces cerevisiae Proteins*
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Signal Transduction
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transformation, Genetic
Substances
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Culture Media
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DNA Transposable Elements
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DNA-Binding Proteins
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MSN2 protein, S cerevisiae
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MSN4 protein, S cerevisiae
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Oxidants
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Protein Kinases
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Rim15 protein, S cerevisiae
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SCH9 protein kinase
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Cyclic AMP-Dependent Protein Kinases
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Adenylyl Cyclases
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Paraquat