@article{1a20a5565d424d66ac273dbcb4b2deeb,
title = "Calorie restriction extends saccharomyces cerevisiae lifespan by increasing respiration",
abstract = "Calorie restriction (CR) extends lifespan in a wide spectrum of organisms and is the only regimen known to lengthen the lifespan of mammals. 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). Lifespan extension in a mutant with reduced PKA activity requires Sir2 and NAD (nicotinamide adenine dinucleotide). 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.",
author = "Lin, {Su Ju} and Matt Kaeberlein and Andalis, {Alex A.} and Sturtz, {Lori A.} and Defossez, {Pierre Antoine} and Culotta, {Valeria C.} and Fink, {Gerald R.} and Leonard Guarente",
note = "Funding Information: We thank S. Royer, C. Williams and K. Mace for technical assistance, and R. Handa, K. Beam, J. Herbers, M. Tamkun and R. Aldrich for discussions about this manuscript. This work was supported by the National Science Foundation (N.E.R.), the Muscular Dystrophy Association (N.E.R.), the March of Dimes (N.E.R.) and an MRC Career Development Award (I.M.R.). Funding Information: We thank D. McNabb and members of the Guarente laboratory for suggestions; J. Smith for providing strains; T. Galitski for his contributions in the development of microarrays and analytical software tools; and T. Ideker for suggestions with microarray analysis. This work was supported by grants to L.G. from the National Institute of Health (NIH), The Ellison Medical Foundation, The Seaver Institute, and the Howard and Linda Stern Fund. S.-J.L. is supported by a NRSA individual award. G.R.F. is supported by the NIH and is an American Cancer Society Professor of Genetics. A.A.A. is supported by the NIH Training Grant in Genomic Sciences, sponsored by the Biotechnology Process Engineering Center. V.C.C. and L.A.S. are supported by grants from the NIH.",
year = "2002",
month = jul,
day = "18",
doi = "10.1038/nature00829",
language = "English (US)",
volume = "418",
pages = "344--348",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6895",
}