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Science 24 January 2003:
Vol. 299. no. 5606, pp. 572 - 574
DOI: 10.1126/science.1078223
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Reports

Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue

Matthias Blüher,1 Barbara B. Kahn,2 C. Ronald Kahn1*

Caloric restriction has been shown to increase longevity in organisms ranging from yeast to mammals. In some organisms, this has been associated with a decreased fat mass and alterations in insulin/insulin-like growth factor 1 (IGF-1) pathways. To further explore these associations with enhanced longevity, we studied mice with a fat-specific insulin receptor knockout (FIRKO). These animals have reduced fat mass and are protected against age-related obesity and its subsequent metabolic abnormalities, although their food intake is normal. Both male and female FIRKO mice were found to have an increase in mean life-span of ~134 days (18%), with parallel increases in median and maximum life-spans. Thus, a reduction of fat mass without caloric restriction can be associated with increased longevity in mice, possibly through effects on insulin signaling.

1 Joslin Diabetes Center and Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA, 02215 USA.
2 Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215 USA.
*   To whom correspondence should be addressed. E-mail: c.ronald.kahn{at}joslin.harvard.edu

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Serum leptin level is a regulator of bone mass.
F. Elefteriou, S. Takeda, K. Ebihara, J. Magre, N. Patano, C. Ae Kim, Y. Ogawa, X. Liu, S. M. Ware, W. J. Craigen, et al. (2004)
PNAS 101, 3258-3263
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Modulation of mammalian life span by the short isoform of p53.
B. Maier, W. Gluba, B. Bernier, T. Turner, K. Mohammad, T. Guise, A. Sutherland, M. Thorner, and H. Scrable (2004)
Genes & Dev. 18, 306-319
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Update on Adipocyte Hormones: Regulation of Energy Balance and Carbohydrate/Lipid Metabolism.
P. J. Havel (2004)
Diabetes 53, S143-151
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Effect of caloric restriction on mitochondrial reactive oxygen species production and bioenergetics: reversal by insulin.
A. J. Lambert and B. J. Merry (2004)
Am J Physiol Regulatory Integrative Comp Physiol 286, R71-R79
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Power to the People.
R. J. Davenport (2003)
Sci. Aging Knowl. Environ. 2003, ns8-8
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Dietary Dehydroepiandrosterone Inhibits Bone Marrow and Leukemia Cell Transplants: Role of Food Restriction.
F. Catalina, L. Milewich, V. Kumar, and M. Bennett (2003)
Experimental Biology and Medicine 228, 1303-1320
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Linking Development and Aging.
B. J. Zwaan (2003)
Sci. Aging Knowl. Environ. 2003, pe32-32
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