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Science 299 (5606): 572-574

Copyright © 2003 by the American Association for the Advancement of Science

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}

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