Effects of lifelong decreased IGF‐1 on physiological status in mice

Caloric restriction(definition) (CR) and repression of the GH/IGF‐1/insulin signaling pathway increase lifespan, possibly via common genetic mechanisms of IGF‐1 regulation and lifespan. To elucidate effects of low plasma and tissue IGF‐1 on longevity, midi (IGF‐1 hypomorph) mice were compared to sex and age matched controls. Bone mineral density (BMD) was examined at 100±8 d (young, n=30) and 495±5 d (old, n=42) by dual energy x‐ray absorptiometry. Metabolic rate (MR), physical activity (PA) and core body temperature (CBT) were concurrently measured over 24 hrs. Data were analyzed by ANOVA with significance at p<0.05. BMD was lower in young midi mice vs. control, with no effect of sex. BMD was lower in old midi mice vs. control, with males exhibiting lower BMD than females. Length and weight were correlated in young and old mice. CBT did not vary by genotype or sex in young mice. CBT was affected by genotype and sex with a sex*genotype in old mice. CBT between young and old midi mice did not differ, though young and old control mice differed. Old midi mice displayed less PA than control with no sex effect. MR differed by genotype and sex with a sex*genotype. Lifelong depressed plasma IGF‐1 leads to some similarity between CR and midi mice (lower CBT, BMD) but not others (MR, PA) suggesting that lowered IGF‐1 is not the major factor involved in the life extending effects of CR. Supported by NIH Grant AG022443, PI C. Sell.