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Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration

Author

Listed:
  • Su-Ju Lin

    (Massachusetts Institute of Technology)

  • Matt Kaeberlein

    (Massachusetts Institute of Technology
    Longenity Inc.)

  • Alex A. Andalis

    (Massachusetts Institute of Technology)

  • Lori A. Sturtz

    (Johns Hopkins University School of Public Health)

  • Pierre-Antoine Defossez

    (Massachusetts Institute of Technology
    CNRS UMR 5665, Ecole Normale Superieure de Lyon)

  • Valeria C. Culotta

    (Johns Hopkins University School of Public Health)

  • Gerald R. Fink

    (Massachusetts Institute of Technology)

  • Leonard Guarente

    (Massachusetts Institute of Technology)

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.

Suggested Citation

  • Su-Ju Lin & Matt Kaeberlein & Alex A. Andalis & Lori A. Sturtz & Pierre-Antoine Defossez & Valeria C. Culotta & Gerald R. Fink & Leonard Guarente, 2002. "Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration," Nature, Nature, vol. 418(6895), pages 344-348, July.
    • Handle: RePEc:nat:nature:v:418:y:2002:i:6895:d:10.1038_nature00829
    DOI: 10.1038/nature00829
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