Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration

Su-Ju Lin, Matt Kaeberlein, Alex A. Andalis, Lori A. Sturtz, Pierre-Antoine Defossez, Valeria C. Culotta, Gerald R. Fink and Leonard Guarente ()
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Su-Ju Lin: Massachusetts Institute of Technology
Matt Kaeberlein: Massachusetts Institute of Technology
Alex A. Andalis: Massachusetts Institute of Technology
Lori A. Sturtz: Johns Hopkins University School of Public Health
Pierre-Antoine Defossez: Massachusetts Institute of Technology
Valeria C. Culotta: Johns Hopkins University School of Public Health
Gerald R. Fink: Massachusetts Institute of Technology
Leonard Guarente: Massachusetts Institute of Technology

Nature, 2002, vol. 418, issue 6895, 344-348

Abstract: Abstract Calorie restriction (CR) extends lifespan in a wide spectrum of organisms and is the only regimen known to lengthen the lifespan of mammals1,2,3,4. We established a model of CR in budding yeast Saccharomyces cerevisiae. In this system, lifespan can be extended by limiting glucose or by reducing the activity of the glucose-sensing cyclic-AMP-dependent kinase (PKA)5. Lifespan extension in a mutant with reduced PKA activity requires Sir2 and NAD (nicotinamide adenine dinucleotide)5. In this study we explore how CR activates Sir2 to extend lifespan. Here we show that the shunting of carbon metabolism toward the mitochondrial tricarboxylic acid cycle and the concomitant increase in respiration play a central part in this process. We discuss how this metabolic strategy may apply to CR in animals.

Date: 2002
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DOI: 10.1038/nature00829

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