Access

Letters to Nature

Nature 418, 344-348 (18 July 2002) | doi:10.1038/nature00829; Received 8 March 2002; Accepted 12 April 2002

Open Innovation Challenges

naturejobs

More science jobs
Post a job for free

Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration

Su-Ju Lin1, Matt Kaeberlein1,2, Alex A. Andalis3, Lori A. Sturtz4, Pierre-Antoine Defossez1,2, Valeria C. Culotta4, Gerald R. Fink3 & Leonard Guarente1

  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  2. Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
  3. Department of Environmental Health Sciences, Johns Hopkins University School of Public Health, Baltimore, Maryland 21205, USA
  4. Present addresses: Longenity Inc., Medford, Massachusetts 02155, USA (M.K.); and CNRS UMR 5665, Ecole Normale Superieure de Lyon, France (P.-A.D.).

Correspondence to: Leonard Guarente1 Correspondence and requests for materials should be addressed to L.G. (e-mail: Email: leng@mit.edu).

Top

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.

  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  2. Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
  3. Department of Environmental Health Sciences, Johns Hopkins University School of Public Health, Baltimore, Maryland 21205, USA
  4. Present addresses: Longenity Inc., Medford, Massachusetts 02155, USA (M.K.); and CNRS UMR 5665, Ecole Normale Superieure de Lyon, France (P.-A.D.).

Correspondence to: Leonard Guarente1 Correspondence and requests for materials should be addressed to L.G. (e-mail: Email: leng@mit.edu).