QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Powers, R. W. Articles by Fields, S. Search for Related Content PubMed PubMed Citation Articles by Powers, R. W., III Articles by Fields, S. Social Bookmarking                   What's this?

RESEARCH PAPER

Extension of chronological life span in yeast by decreased TOR pathway signaling

¹ Departments of Genome Sciences and Medicine, ² Molecular and Cellular Biology Program, ³ Department of Biochemistry, ⁴ The Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA

Chronological life span (CLS) in Saccharomyces cerevisiae, defined as the time cells in a stationary phase culture remain viable, has been proposed as a model for the aging of post-mitotic tissues in mammals. We developed a high-throughput assay to determine CLS for 4800 single-gene deletion strains of yeast, and identified long-lived strains carrying mutations in the conserved TOR pathway. TOR signaling regulates multiple cellular processes in response to nutrients, especially amino acids, raising the possibility that decreased TOR signaling mediates life span extension by calorie restriction. In support of this possibility, removal of either asparagine or glutamate from the media significantly increased stationary phase survival. Pharmacological inhibition of TOR signaling by methionine sulfoximine or rapamycin also increased CLS. Decreased TOR activity also promoted increased accumulation of storage carbohydrates and enhanced stress resistance and nuclear relocalization of the stress-related transcription factor Msn2. We propose that up-regulation of a highly conserved response to starvation-induced stress is important for life span extension by decreased TOR signaling in yeast and higher eukaryotes.

[Keywords: Saccharomyces cerevisiae; TOR; aging; life span; nutrients; yeast]

Received October 3, 2005; revised version accepted November 22, 2005.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1381406.

⁵ Corresponding author.
E-MAIL fields{at}u.washington.edu; FAX (206) 543-0754.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Lavoie and M. Whiteway Increased Respiration in the sch9{Delta} Mutant Is Required for Increasing Chronological Life Span but Not Replicative Life Span Eukaryot. Cell, July 1, 2008; 7(7): 1127 - 1135. [Abstract] [Full Text] [PDF]

				G. S. Shadel Expression and Maintenance of Mitochondrial DNA: New Insights into Human Disease Pathology Am. J. Pathol., June 1, 2008; 172(6): 1445 - 1456. [Abstract] [Full Text] [PDF]

				V. M. Boer, S. Amini, and D. Botstein Influence of genotype and nutrition on survival and metabolism of starving yeast PNAS, May 13, 2008; 105(19): 6930 - 6935. [Abstract] [Full Text] [PDF]

				G. Luo, A. Gruhler, Y. Liu, O. N. Jensen, and R. C. Dickson The Sphingolipid Long-chain Base-Pkh1/2-Ypk1/2 Signaling Pathway Regulates Eisosome Assembly and Turnover J. Biol. Chem., April 18, 2008; 283(16): 10433 - 10444. [Abstract] [Full Text] [PDF]

				A. D. Aragon, A. L. Rodriguez, O. Meirelles, S. Roy, G. S. Davidson, P. H. Tapia, C. Allen, R. Joe, D. Benn, and M. Werner-Washburne Characterization of Differentiated Quiescent and Nonquiescent Cells in Yeast Stationary-Phase Cultures Mol. Biol. Cell, March 1, 2008; 19(3): 1271 - 1280. [Abstract] [Full Text] [PDF]

				C. J. Murakami, C. R. Burtner, B. K. Kennedy, and M. Kaeberlein A Method for High-Throughput Quantitative Analysis of Yeast Chronological Life Span J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2008; 63(2): 113 - 121. [Abstract] [Full Text] [PDF]

				G. Yiu, A. McCord, A. Wise, R. Jindal, J. Hardee, A. Kuo, M. Y. Shimogawa, L. Cahoon, M. Wu, J. Kloke, et al. Pathways Change in Expression During Replicative Aging in Saccharomyces cerevisiae J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2008; 63(1): 21 - 34. [Abstract] [Full Text] [PDF]

				A. Fredriksson, M. Ballesteros, C. N. Peterson, O. Persson, T. J. Silhavy, and T. Nystrom Decline in ribosomal fidelity contributes to the accumulation and stabilization of the master stress response regulator {sigma}S upon carbon starvation Genes & Dev., April 1, 2007; 21(7): 862 - 874. [Abstract] [Full Text] [PDF]

				P. H. Patel and F. Tamanoi Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress J. Cell Sci., October 15, 2006; 119(20): 4285 - 4292. [Abstract] [Full Text] [PDF]

				S. M. Schieke, D. Phillips, J. P. McCoy Jr., A. M. Aponte, R.-F. Shen, R. S. Balaban, and T. Finkel The Mammalian Target of Rapamycin (mTOR) Pathway Regulates Mitochondrial Oxygen Consumption and Oxidative Capacity J. Biol. Chem., September 15, 2006; 281(37): 27643 - 27652. [Abstract] [Full Text] [PDF]

				E. Kvam and D. S. Goldfarb Structure and function of nucleus-vacuole junctions: outer-nuclear-membrane targeting of Nvj1p and a role in tryptophan uptake J. Cell Sci., September 1, 2006; 119(17): 3622 - 3633. [Abstract] [Full Text] [PDF]

				M. Leslie Craving an answer. Sci. Aging Knowl. Environ., February 15, 2006; 2006(6): nf7 - nf7. [Abstract] [Full Text]