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Science 14 November 1997:
Vol. 278. no. 5341, pp. 1319 - 1322
DOI: 10.1126/science.278.5341.1319
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Reports

daf-16: An HNF-3/forkhead Family Member That Can Function to Double the Life-Span of Caenorhabditis elegans

Kui Lin, Jennie B. Dorman, * Aylin Rodan, Cynthia Kenyon

The wild-type Caenorhabditis elegans nematode ages rapidly, undergoing development, senescence, and death in less than 3 weeks. In contrast, mutants with reduced activity of the gene daf-2, a homolog of the insulin and insulin-like growth factor receptors, age more slowly than normal and live more than twice as long. These mutants are active and fully fertile and have normal metabolic rates. The life-span extension caused by daf-2 mutations requires the activity of the gene daf-16. daf-16 appears to play a unique role in life-span regulation and encodes a member of the hepatocyte nuclear factor 3 (HNF-3)/forkhead family of transcriptional regulators. In humans, insulin down-regulates the expression of certain genes by antagonizing the activity of HNF-3, raising the possibility that aspects of this regulatory system have been conserved.

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-0554, USA.
*   Present address: Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195- 7275, USA.

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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 »
SH2-B Is a Positive Regulator of Nerve Growth Factor-mediated Activation of the Akt/Forkhead Pathway in PC12 Cells.
X. Wang, L. Chen, T. J. Maures, J. Herrington, and C. Carter-Su (2004)
J. Biol. Chem. 279, 133-141
   Abstract »    Full Text »    PDF »
Insulin Inhibition of Transcription Stimulated by the Forkhead Protein Foxo1 Is Not Solely due to Nuclear Exclusion.
W.-C. Tsai, N. Bhattacharyya, L.-Y. Han, J. A. Hanover, and M. M. Rechler (2003)
Endocrinology 144, 5615-5622
   Abstract »    Full Text »    PDF »
Convergence of Peroxisome Proliferator-activated Receptor {gamma} and Foxo1 Signaling Pathways.
P. Dowell, T. C. Otto, S. Adi, and M. D. Lane (2003)
J. Biol. Chem. 278, 45485-45491
   Abstract »    Full Text »    PDF »
Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans.
M. Barbieri, M. Bonafe, C. Franceschi, and G. Paolisso (2003)
Am J Physiol Endocrinol Metab 285, E1064-E1071
   Abstract »    Full Text »    PDF »
Neutrophil activation by fMLP regulates FOXO (forkhead) transcription factors by multiple pathways, one of which includes the binding of FOXO to the survival factor Mcl-1.
L. J. Crossley (2003)
J. Leukoc. Biol. 74, 583-592
   Abstract »    Full Text »    PDF »
Insulin's expanding control of forkheads.
M. P. Czech (2003)
PNAS 100, 11198-11200
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