MicroRNA‐150 Knockout (miR150‐KO) Prevents Age‐Related Glucose Intolerance and Extends Life‐Span

Abstract

Background and HypothesesAgeing is associated with metabolic syndrome. The purpose of this study is to assess if miR150 regulates glucose tolerance, insulin sensitivity, and lifespan in male mice.Methods and ResultsThirteen wild‐type (WT) and 32 Mir150‐KO male mice were used. Mir150‐KO decreased insulin sensitivity and improved aging‐related glucose intolerance. Mir150‐KO extended lifespan in male mice compared with the age‐matched WT mice. The longest lifespan was 37 months in Mir150‐KO mice and 30 months for WT controls (p<0.05 Kaplan Meier Analysis). The survival percentage was 28.1% in the Mir150‐KO group and 7.7% in the wild type group at the age of 30 months. IHC data showed that the pancreatic insulin content was increased by Mir150‐KO. Western blot analysis indicated that Mir150‐KO decreased insulin/IGF‐1 receptor and Akt activity in the kidneys but increased ACCs and p‐ACCs in the liver of aged mice.ConclusionMir150‐KO extended lifespan by suppressing the renal insulin/IGF‐1/Akt activity and upregulating the hepatic ACC activity.