Caffeine extends yeast lifespan by targeting TORC1

V Wanke, E Cameroni, A Uotila, M Piccolis… - Molecular …, 2008 - Wiley Online Library
V Wanke, E Cameroni, A Uotila, M Piccolis, J Urban, R Loewith, C De Virgilio
Molecular microbiology, 2008Wiley Online Library
Dietary nutrient limitation (dietary restriction) is known to increase lifespan in a variety of
organisms. Although the molecular events that couple dietary restriction to increased
lifespan are not clear, studies of the model eukaryote Saccharomyces cerevisiae have
implicated several nutrient‐sensitive kinases, including the t arget ofr apamycin c omplex 1
(TORC1), Sch9, protein kinase A (PKA) and Rim15. We have recently demonstrated that
TORC1 activates Sch9 by direct phosphorylation. We now show that Sch9 inhibits Rim15 …
Summary
Dietary nutrient limitation (dietary restriction) is known to increase lifespan in a variety of organisms. Although the molecular events that couple dietary restriction to increased lifespan are not clear, studies of the model eukaryote Saccharomyces cerevisiae have implicated several nutrient‐sensitive kinases, including the target of rapamycin complex 1 (TORC1), Sch9, protein kinase A (PKA) and Rim15. We have recently demonstrated that TORC1 activates Sch9 by direct phosphorylation. We now show that Sch9 inhibits Rim15 also by direct phosphorylation. Treatment of yeast cells with the specific TORC1 inhibitor rapamycin or caffeine releases Rim15 from TORC1‐Sch9‐mediated inhibition and consequently increases lifespan. This kinase cascade appears to have been evolutionarily conserved, suggesting that caffeine may extend lifespan in other eukaryotes, including man.
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