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Science 6 April 2001:
Vol. 292. no. 5514, pp. 107 - 110
DOI: 10.1126/science.1057987
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Reports

A Mutant Drosophila Insulin Receptor Homolog That Extends Life-Span and Impairs Neuroendocrine Function

M. Tatar,1* A. Kopelman,1 D. Epstein,1 M.-P. Tu,12 C.-M. Yin,2 R. S. Garofalo3

The Drosophila melanogaster gene insulin-like receptor (InR) is homologous to mammalian insulin receptors as well as to Caenorhabditis elegans daf-2, a signal transducer regulating worm dauer formation and adult longevity. We describe a heteroallelic, hypomorphic genotype of mutant InR, which yields dwarf females with up to an 85% extension of adult longevity and dwarf males with reduced late age-specific mortality. Treatment of the long-lived InR dwarfs with a juvenile hormone analog restores life expectancy toward that of wild-type controls. We conclude that juvenile hormone deficiency, which results from InR signal pathway mutation, is sufficient to extend life-span, and that in flies, insulin-like ligands nonautonomously mediate aging through retardation of growth or activation of specific endocrine tissue.

1 Brown University, Providence, RI 02912, USA.
2 University of Massachusetts, Amherst, MA 01003, USA.
3 Pfizer Global Research and Development, Groton, CT 06340, USA.
*   To whom correspondence should be addressed. E-mail: Marc_Tatar{at}Brown.edu

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Structural, Biochemical, and Expression Analysis of Two Distinct Insulin-Like Growth Factor I Receptors and Their Ligands in Zebrafish.
T. Maures, S. J. Chan, B. Xu, H. Sun, J. Ding, and C. Duan (2002)
Endocrinology 143, 1858-1871
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High-quality life extension by the enzyme peptide methionine sulfoxide reductase.
H. Ruan, X. D. Tang, M.-L. Chen, M.-L. A. Joiner, G. Sun, N. Brot, H. Weissbach, S. H. Heinemann, L. Iverson, C.-F. Wu, et al. (2002)
PNAS 99, 2748-2753
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Growth Hormone-Induced Alterations in the Insulin-Signaling System.
F. P. Dominici and D. Turyn (2002)
Experimental Biology and Medicine 227, 149-157
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Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Hepatocyte Antioxidative Enzymes.
H. M. Brown-Borg, S. G. Rakoczy, M. A. Romanick, and M. A. Kennedy (2002)
Experimental Biology and Medicine 227, 94-104
   Abstract »    Full Text »    PDF »
Regulation of Aging by Germline Stem Cells.
M. Tatar (2002)
Sci. Aging Knowl. Environ. 2002, pe2-2
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