Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Logo for

Science 298 (5594): 830-834

Copyright © 2002 by the American Association for the Advancement of Science

Timing Requirements for Insulin/IGF-1 Signaling in C. elegans

Andrew Dillin,* Douglas K. Crawford, Cynthia Kenyondagger

The insulin/IGF-1 (where IGF-1 is insulin-like growth factor-1) signaling pathway influences longevity, reproduction, and diapause in many organisms. Because of the fundamental importance of this system in animal physiology, we asked when during the animal's life it is required to regulate these different processes. We find that in Caenorhabditis elegans, the pathway acts during adulthood, to relatively advanced ages, to influence aging. In contrast, it regulates diapause during development. In addition, the pathway controls longevity and reproduction independently of one another. Together our findings show that life-span regulation can be dissociated temporally from phenotypes that might seem to decrease the quality of life.

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143-0448, USA.
*   Present address: Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

dagger    To whom correspondence should be addressed. E-mail: ckenyon{at}biochem.ucsf.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Systematic Identification of Gene Activities Promoting Hypoxic Death.
M. E. Mabon, X. Mao, Y. Jiao, B. A. Scott, and C. M. Crowder (2009)
Genetics 181, 483-496
   Abstract »    Full Text »    PDF »
Stem Cells, Their Niches and the Systemic Environment: An Aging Network.
D. Drummond-Barbosa (2008)
Genetics 180, 1787-1797
   Abstract »    Full Text »    PDF »
C. elegans dauer formation and the molecular basis of plasticity.
N. Fielenbach and A. Antebi (2008)
Genes & Dev. 22, 2149-2165
   Abstract »    Full Text »    PDF »
PKC-Induced Intracellular Trafficking of CaV2 Precedes Its Rapid Recruitment to the Plasma Membrane.
Y. Zhang, J. S. Helm, A. Senatore, J. D. Spafford, L. K. Kaczmarek, and E. A. Jonas (2008)
J. Neurosci. 28, 2601-2612
   Abstract »    Full Text »    PDF »
Akt and CHIP coregulate tau degradation through coordinated interactions.
C. A. Dickey, J. Koren, Y.-J. Zhang, Y.-f. Xu, U. K. Jinwal, M. J. Birnbaum, B. Monks, M. Sun, J. Q. Cheng, C. Patterson, et al. (2008)
PNAS 105, 3622-3627
   Abstract »    Full Text »    PDF »
DAF-16-Dependent Suppression of Immunity During Reproduction in Caenorhabditis elegans.
S. Miyata, J. Begun, E. R. Troemel, and F. M. Ausubel (2008)
Genetics 178, 903-918
   Abstract »    Full Text »    PDF »
Distinct Activities of the Germline and Somatic Reproductive Tissues in the Regulation of Caenorhabditis elegans' Longevity.
T. M. Yamawaki, N. Arantes-Oliveira, J. R. Berman, P. Zhang, and C. Kenyon (2008)
Genetics 178, 513-526
   Abstract »    Full Text »    PDF »
Hydrogen sulfide increases thermotolerance and lifespan in Caenorhabditis elegans.
D. L. Miller and M. B. Roth (2007)
PNAS 104, 20618-20622
   Abstract »    Full Text »    PDF »
Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans.
C. T. Murphy, S.-J. Lee, and C. Kenyon (2007)
PNAS 104, 19046-19050
   Abstract »    Full Text »    PDF »
Arabidopsis CPR5 is a senescence-regulatory gene with pleiotropic functions as predicted by the evolutionary theory of senescence.
H.-C. Jing, L. Anderson, M. J.G. Sturre, J. Hille, and P. P. Dijkwel (2007)
J. Exp. Bot.
   Abstract »    Full Text »    PDF »
Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants.
A. V. Samuelson, C. E. Carr, and G. Ruvkun (2007)
Genes & Dev. 21, 2976-2994
   Abstract »    Full Text »    PDF »
Caenorhabditis elegans SDF-9 Enhances Insulin/Insulin-Like Signaling Through Interaction With DAF-2.
V. L. Jensen, P. S. Albert, and D. L. Riddle (2007)
Genetics 177, 661-666
   Abstract »    Full Text »    PDF »
Quantitative Mass Spectrometry Identifies Insulin Signaling Targets in C. elegans.
M.-Q. Dong, J. D. Venable, N. Au, T. Xu, S. K. Park, D. Cociorva, J. R. Johnson, A. Dillin, and J. R. Yates III (2007)
Science 317, 660-663
   Abstract »    Full Text »    PDF »
Specificity and Complexity of the Caenorhabditis elegans Innate Immune Response.
S. Alper, S. J. McBride, B. Lackford, J. H. Freedman, and D. A. Schwartz (2007)
Mol. Cell. Biol. 27, 5544-5553
   Abstract »    Full Text »    PDF »
Temporal and spatial transcriptional profiles of aging in Drosophila melanogaster.
M. Zhan, H. Yamaza, Y. Sun, J. Sinclair, H. Li, and S. Zou (2007)
Genome Res. 17, 1236-1243
   Abstract »    Full Text »    PDF »
Vitellogenin, juvenile hormone, insulin signaling, and queen honey bee longevity.
M. Corona, R. A. Velarde, S. Remolina, A. Moran-Lauter, Y. Wang, K. A. Hughes, and G. E. Robinson (2007)
PNAS 104, 7128-7133
   Abstract »    Full Text »    PDF »
Genetic modulation of hormone levels and life span in hybrids between laboratory and wild-derived mice..
J. M. Harper, S. J. Durkee, R. C. Dysko, S. N. Austad, and R. A. Miller (2006)
J. Gerontol. A Biol. Sci. Med. Sci. 61, 1019-1029
   Abstract »    Full Text »    PDF »
Opposing Activities Protect Against Age-Onset Proteotoxicity.
E. Cohen, J. Bieschke, R. M. Perciavalle, J. W. Kelly, and A. Dillin (2006)
Science 313, 1604-1610
   Abstract »    Full Text »    PDF »
No extension of lifespan by ablation of germ line in Drosophila.
A. I Barnes, J. M Boone, J. Jacobson, L. Partridge, and T. Chapman (2006)
Proc R Soc B 273, 939-947
   Abstract »    Full Text »    PDF »
From the Cover: Reproductive protein protects functionally sterile honey bee workers from oxidative stress.
S.-C. Seehuus, K. Norberg, U. Gimsa, T. Krekling, and G. V. Amdam (2006)
PNAS 103, 962-967
   Abstract »    Full Text »    PDF »
The Hexosamine Signaling Pathway: Deciphering the "O-GlcNAc Code".
D. C. Love and J. A. Hanover (2005)
Sci. STKE 2005, re13
   Abstract »    Full Text »    PDF »
Aging-Dependent and -Independent Modulation of Associative Learning Behavior by Insulin/Insulin-Like Growth Factor-1 Signal in Caenorhabditis elegans.
H. Murakami, K. Bessinger, J. Hellmann, and S. Murakami (2005)
J. Neurosci. 25, 10894-10904
   Abstract »    Full Text »    PDF »
Interfering with Longevity.
S. S. Lee (2005)
Sci. Aging Knowl. Environ. 2005, pe26
   Abstract »    Full Text »
Insulin Signaling in the Central Nervous System: A Critical Role in Metabolic Homeostasis and Disease From C. elegans to Humans.
D. Porte Jr., D. G. Baskin, and M. W. Schwartz (2005)
Diabetes 54, 1264-1276
   Abstract »    Full Text »    PDF »
Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands.
S. J. Broughton, M. D. W. Piper, T. Ikeya, T. M. Bass, J. Jacobson, Y. Driege, P. Martinez, E. Hafen, D. J. Withers, S. J. Leevers, et al. (2005)
PNAS 102, 3105-3110
   Abstract »    Full Text »    PDF »
Response to Comment on "Long-Lived Drosophila with Overexpressed dFOXO in Adult Fat Body".
M. E. Giannakou, M. Goss, M. A. Junger, E. Hafen, S. J. Leevers, and L. Partridge (2005)
Science 307, 675b
   Full Text »    PDF »
A more efficient search strategy for aging genes based on connectivity.
L. Ferrarini, L. Bertelli, J. Feala, A. D. McCulloch, and G. Paternostro (2005)
Bioinformatics 21, 338-348
   Abstract »    Full Text »    PDF »
Sexual and Temporal Dynamics of Molecular Evolution in C. elegans Development.
A. D. Cutter and S. Ward (2005)
Mol. Biol. Evol. 22, 178-188
   Abstract »    Full Text »    PDF »
Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae.
P. Fabrizio, L. Battistella, R. Vardavas, C. Gattazzo, L.-L. Liou, A. Diaspro, J. W. Dossen, E. B. Gralla, and V. D. Longo (2004)
J. Cell Biol. 166, 1055-1067
   Abstract »    Full Text »    PDF »
Deletion of the Intestinal Peptide Transporter Affects Insulin and TOR Signaling in Caenorhabditis elegans.
B. Meissner, M. Boll, H. Daniel, and R. Baumeister (2004)
J. Biol. Chem. 279, 36739-36745
   Abstract »    Full Text »    PDF »
Emerging Technologies: Trendy RNA Tools for Aging Research.
C. C. Deocaris, S. C. Kaul, K. Taira, and R. Wadhwa (2004)
J. Gerontol. A Biol. Sci. Med. Sci. 59, B771-B783
   Abstract »    Full Text »    PDF »
Long-Lived Drosophila with Overexpressed dFOXO in Adult Fat Body.
M. E. Giannakou, M. Goss, M. A. Junger, E. Hafen, S. J. Leevers, and L. Partridge (2004)
Science 305, 361
   Abstract »    Full Text »    PDF »
Inside Insulin Signaling, Communication Is Key to Long Life.
A. Antebi (2004)
Sci. Aging Knowl. Environ. 2004, pe25
   Abstract »    Full Text »
Come One, Come All.
S. S. Lee (2004)
Sci. Aging Knowl. Environ. 2004, pe18
   Abstract »    Full Text »
Intercellular signaling of reproductive development by the C. elegans DAF-9 cytochrome P450.
H. Y. Mak and G. Ruvkun (2004)
Development 131, 1777-1786
   Abstract »    Full Text »    PDF »
Regulation of Longevity in Caenorhabditis elegans by Heat Shock Factor and Molecular Chaperones.
J. F. Morley and R. I. Morimoto (2004)
Mol. Biol. Cell 15, 657-664
   Abstract »    Full Text »    PDF »
Molecular Mechanism of Maternal Rescue in the clk-1 Mutants of Caenorhabditis elegans.
J. Burgess, A. K. Hihi, C. Y. Benard, R. Branicky, and S. Hekimi (2003)
J. Biol. Chem. 278, 49555-49562
   Abstract »    Full Text »    PDF »
Effects of Exogenous Melatonin--A Review.
V. N. Anisimov (2003)
Toxicol Pathol 31, 589-603
   Abstract »    PDF »
SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response.
J. H. An and T. K. Blackwell (2003)
Genes & Dev. 17, 1882-1893
   Abstract »    Full Text »    PDF »
Caloric Restriction in trans.
B. S. Kristal and U. Paolucci (2003)
Sci. Aging Knowl. Environ. 2003, pe19-19
   Abstract »    Full Text »
Evolutionary Medicine: From Dwarf Model Systems to Healthy Centenarians?.
V. D. Longo and C. E. Finch (2003)
Science 299, 1342-1346
   Abstract »    Full Text »    PDF »
The Endocrine Regulation of Aging by Insulin-like Signals.
M. Tatar, A. Bartke, and A. Antebi (2003)
Science 299, 1346-1351
   Abstract »    Full Text »    PDF »
Genetics and the Specificity of the Aging Process.
S. Hekimi and L. Guarente (2003)
Science 299, 1351-1354
   Abstract »    Full Text »    PDF »
Rates of Behavior and Aging Specified by Mitochondrial Function During Development.
A. Dillin, A.-L. Hsu, N. Arantes-Oliveira, J. Lehrer-Graiwer, H. Hsin, A. G. Fraser, R. S. Kamath, J. Ahringer, and C. Kenyon (2002)
Science 298, 2398-2401
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882