he causal relationships betweenย insulin levels, insulin resistance, andย longevityย are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalianย lifespan, but insulin resistance, a natural form of decreasedย insulin signaling, is associated with greater risk of age-related disease in mammals. We comparedย Ins2+/โย mice toย Ins2+/+littermate controls, on a genetically stableย Ins1nullย background.ย Proteomicย andย transcriptomicanalyses of livers from 25-week-old mice suggested potential for healthier aging and alteredย insulin sensitivityย inย Ins2+/โย mice. Halvingย Ins2ย lowered circulating insulinย by 25%โ34% in aged female mice, without alteringย Igf1ย or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover,ย lowered insulin caused significantย 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.
Mandatory FDA Disclaimer: Not intended to diagnose, treat, cure or prevent any disease.
Mandatory FDA Disclaimer: Not intended to diagnose, treat, cure or prevent any disease.
