Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue

Blüher, Matthias; Kahn, Barbara B.; Kahn, C. Ronald

doi:10.1126/science.1078223

Cited by 1,155

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Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue

Blüher, Matthias, Kahn, Barbara B., Kahn, C. Ronald·2003·Science

DOI 10.1126/science.1078223

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Abstract

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.

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Studies with genetically modified mice, as well as by means of ectopic treatments, have proved that it is possible to ameliorate various age-related parameters (health-span), which is often accompanied by an increase of life-span.
“Studies with genetically modified mice, as well as by means of ectopic treatments, have proved that it is possible to ameliorate various age-related parameters (the so-called ‘health-span’), which is often accompanied by an increase of life-span (Bluher et al, 2003; Conboy et al, 2005; Flurkey et al, 2001; Harrison et al, 2009; Holzenberger et al, 2003; Tomas-Loba et al, 2008).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Bluher et al, 2003

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Harrison, D. E., & Archer, J. R. (1987) · The Journal of Nutrition · doi:10.1093/jn/117.2.376 · Cited by 133

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“…were suppressed, and Foxo3a was up-regulated transiently in the cerebral cortex in response to DNP. Down-regulation of insulin receptor signaling may contribute to the mechanism whereby caloric restriction extends longevity in animal models of aging (Bl€uher et al. 2003; Mercken et al. 2013).”
Background
Revisiting an age-old question regarding oxidative stress
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The role of insulin and insulin-like growth factor-I in mammalian ageing
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Authors: Blüher, M., Kahn, B. B., & Kahn, C. R.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2003-01-24
Volume: 299
Issue: 5606
Pages: 572-574
ISSN: 0036-8075
1095-9203
DOI: 10.1126/science.1078223
Cited by: 1,155
References: 2
Language: en

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Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue

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