INSULIN & AGING

insulin & aging


Reduced Circulating Insulin Enhances Insulin Sensitivity and Extends Lifespan


The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+littermate controls, on a genetically stable Ins1null background. Proteomic and transcriptomicanalyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.


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  254. DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth
  255. insulin‐like growth factor‐I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats
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  257. Dietary (−)-Epigallocatechin-3-gallate supplementation counteracts aging-associated skeletal muscle insulin resistance and fatty liver in senescence-accelerated …
  258. Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 levels in aging and age-associated diseases
  259. Post-developmental microRNA expression is required for normal physiology, and regulates aging in parallel to insulin/IGF-1 signaling in C. elegans
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