HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 43, 44533-44543, October 22, 2004

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 279/43/44533    most recent M406207200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McElwee, J. J. Articles by Gems, D. Search for Related Content PubMed PubMed Citation Articles by McElwee, J. J. Articles by Gems, D. Social Bookmarking                      What's this?

Shared Transcriptional Signature in Caenorhabditis elegans Dauer Larvae and Long-lived daf-2 Mutants Implicates Detoxification System in Longevity Assurance^*

Joshua J. McElwee, Eugene Schuster, Eric Blanc, James H. Thomas¶, and David Gems||

From the Department of Biology, University College London, WC1E 6BT, European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, United Kingdom, and the ^¶Department of Genome Science, University of Washington, Seattle, Washington 98195

In the nematode Caenorhabditis elegans, formation of the long-lived dauer larva and adult aging are both controlled by insulin/insulin-like growth factor-1 signaling. Potentially, increased adult life span in daf-2 insulin/insulin-like growth factor-1 receptor mutants results from mis-expression in the adult of a dauer larva longevity program. By using oligonucleotide microarray analysis, we identified a dauer transcriptional signature in daf-2 mutant adults. By means of a nonbiased statistical approach, we identified gene classes whose expression is altered similarly in dauers and daf-2 mutants, which represent potential determinants of life span. These include known determinants of longevity; the small heat shock protein/-crystallins are up-regulated in both milieus. The cytochrome P450, short-chain dehydrogenase/reductase, UDP-glucuronosyltransferase, and glutathione S-transferase (in daf-2 mutants) gene classes were also up-regulated. These four gene classes act together in metabolism and excretion of toxic endobiotic and xenobiotic metabolites. This suggests that diverse toxic lipophilic and electrophilic metabolites, disposed of by phase 1 and phase 2 drug metabolism, may be the major determinants of the molecular damage that causes aging. In addition, we observed down-regulation of genes linked to nutrient uptake, including nhx-2 and pep-2. These work together in the uptake of dipeptides in the intestine, implying dietary restriction in daf-2 mutants. Some gene groups up-regulated in dauers and/or daf-2 were enriched for certain promoter elements as follows: the daf-16-binding element, the heat shock-response element, the heat shock-associated sequence, or the hif-1-response element. By contrast, the daf-16-associated element was enriched in genes down-regulated in dauers and daf-2 mutants. Thus, particular promoter elements appear longevity-associated or aging associated.

Received for publication, June 3, 2004 , and in revised form, August 9, 2004.

^* This work was supported by grants from the Wellcome Trust, Functional Genomic Analysis of Aging (to J. J. M., E. S., E. B., and D. G.), and from the Royal Society (to D. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Fig. 1, Tables I–III, additional text, and additional Refs. 1–7.

^|| To whom all correspondence should be addressed: Dept. of Biology, University College London, Gower St., London WC1E 6BT, UK. Tel.: 44-207-679-4381; Fax.: 44-207-679-7096; E-mail: david.gems{at}ucl.ac.uk.

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

This article has been cited by other articles:

				M. M. Gaglia and C. Kenyon Stimulation of Movement in a Quiescent, Hibernation-Like Form of Caenorhabditis elegans by Dopamine Signaling J. Neurosci., June 3, 2009; 29(22): 7302 - 7314. [Abstract] [Full Text] [PDF]

				R. Mehta, K. A. Steinkraus, G. L. Sutphin, F. J. Ramos, L. S. Shamieh, A. Huh, C. Davis, D. Chandler-Brown, and M. Kaeberlein Proteasomal Regulation of the Hypoxic Response Modulates Aging in C. elegans Science, May 29, 2009; 324(5931): 1196 - 1198. [Abstract] [Full Text] [PDF]

				M. E. Mabon, X. Mao, Y. Jiao, B. A. Scott, and C. M. Crowder Systematic Identification of Gene Activities Promoting Hypoxic Death Genetics, February 1, 2009; 181(2): 483 - 496. [Abstract] [Full Text] [PDF]

				H. Schulenburg, J. Kurtz, Y. Moret, and M. T Siva-Jothy Introduction. Ecological immunology Phil Trans R Soc B, January 12, 2009; 364(1513): 3 - 14. [Abstract] [Full Text] [PDF]

				A. L. Fisher, K. E. Page, G. J. Lithgow, and L. Nash The Caenorhabditis elegans K10C2.4 Gene Encodes a Member of the Fumarylacetoacetate Hydrolase Family: A CAENORHABDITIS ELEGANS MODEL OF TYPE I TYROSINEMIA J. Biol. Chem., April 4, 2008; 283(14): 9127 - 9135. [Abstract] [Full Text] [PDF]

				D. S. Patel, A. Garza-Garcia, M. Nanji, J. J. McElwee, D. Ackerman, P. C. Driscoll, and D. Gems Clustering of Genetically Defined Allele Classes in the Caenorhabditis elegans DAF-2 Insulin/IGF-1 Receptor Genetics, February 1, 2008; 178(2): 931 - 946. [Abstract] [Full Text] [PDF]

				M. Waters, S. Stasiewicz, B. Alex Merrick, K. Tomer, P. Bushel, R. Paules, N. Stegman, G. Nehls, K. J. Yost, C. H. Johnson, et al. CEBS Chemical Effects in Biological Systems: a public data repository integrating study design and toxicity data with microarray and proteomics data Nucleic Acids Res., January 11, 2008; 36(suppl_1): D892 - D900. [Abstract] [Full Text] [PDF]

				M. Hasshoff, C. Bohnisch, D. Tonn, B. Hasert, and H. Schulenburg The role of Caenorhabditis elegans insulin-like signaling in the behavioral avoidance of pathogenic Bacillus thuringiensis FASEB J, June 1, 2007; 21(8): 1801 - 1812. [Abstract] [Full Text] [PDF]

				C. Selman, N. D. Kerrison, A. Cooray, M. D. W. Piper, S. J. Lingard, R. H. Barton, E. F. Schuster, E. Blanc, D. Gems, J. K. Nicholson, et al. Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice Physiol Genomics, November 21, 2006; 27(3): 187 - 200. [Abstract] [Full Text] [PDF]

				A. R. Mendenhall, B. LaRue, and P. A. Padilla Glyceraldehyde-3-Phosphate Dehydrogenase Mediates Anoxia Response and Survival in Caenorhabditis elegans Genetics, November 1, 2006; 174(3): 1173 - 1187. [Abstract] [Full Text] [PDF]

				R. Baumeister, E. Schaffitzel, and M. Hertweck Endocrine signaling in Caenorhabditis elegans controls stress response and longevity. J. Endocrinol., August 1, 2006; 190(2): 191 - 202. [Abstract] [Full Text] [PDF]

				D. O'Rourke, D. Baban, M. Demidova, R. Mott, and J. Hodgkin Genomic clusters, putative pathogen recognition molecules, and antimicrobial genes are induced by infection of C. elegans with M. nematophilum Genome Res., August 1, 2006; 16(8): 1005 - 1016. [Abstract] [Full Text] [PDF]

				M. C. W. van den Berg, J. Z. Woerlee, H. Ma, and R. C. May Sex-Dependent Resistance to the Pathogenic Fungus Cryptococcus neoformans Genetics, June 1, 2006; 173(2): 677 - 683. [Abstract] [Full Text] [PDF]

				P. Mourikis, G. D. Hurlbut, and S. Artavanis-Tsakonas Enigma, a mitochondrial protein affecting lifespan and oxidative stress response in Drosophila PNAS, January 31, 2006; 103(5): 1307 - 1312. [Abstract] [Full Text] [PDF]

				H. Li and M. Zhan Systematic intervention of transcription for identifying network response to disease and cellular phenotypes Bioinformatics, January 1, 2006; 22(1): 96 - 102. [Abstract] [Full Text] [PDF]

				J. C. Corton and H. M. Brown-Borg Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1 in Caloric Restriction and Other Models of Longevity J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2005; 60(12): 1494 - 1509. [Abstract] [Full Text] [PDF]

				T. Yabe, N. Suzuki, T. Furukawa, T. Ishihara, and I. Katsura Multidrug resistance-associated protein MRP-1 regulates dauer diapause by its export activity in Caenorhabditis elegans Development, July 15, 2005; 132(14): 3197 - 3207. [Abstract] [Full Text] [PDF]

				C. Shen, D. Nettleton, M. Jiang, S. K. Kim, and J. A. Powell-Coffman Roles of the HIF-1 Hypoxia-inducible Factor during Hypoxia Response in Caenorhabditis elegans J. Biol. Chem., May 27, 2005; 280(21): 20580 - 20588. [Abstract] [Full Text] [PDF]

				J. C. Greene, A. J. Whitworth, L. A. Andrews, T. J. Parker, and L. J. Pallanck Genetic and genomic studies of Drosophila parkin mutants implicate oxidative stress and innate immune responses in pathogenesis Hum. Mol. Genet., March 15, 2005; 14(6): 799 - 811. [Abstract] [Full Text] [PDF]

				C. L. Brett, M. Donowitz, and R. Rao Evolutionary origins of eukaryotic sodium/proton exchangers Am J Physiol Cell Physiol, February 1, 2005; 288(2): C223 - C239. [Abstract] [Full Text] [PDF]