Extended longevity in mice lacking the insulin receptor in adipose tissue.
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 approximately 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.
Blüher
Matthias
M
Joslin Diabetes Center and Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA, 02215 USA.
Kahn
Barbara B
BB
Kahn
C Ronald
CR
D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000378:metabolism*; D000375:Aging; D000818:Animals; D001824:Body Constitution; D001835:Body Weight; D031204:Caloric Restriction; D004435:Eating; D005260:Female; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008136:Longevity; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013851:Thinness
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin