Metformin improves healthspan and lifespan in mice

Nat Commun. 2013;4:2192. doi: 10.1038/ncomms3192.

Abstract

Metformin is a drug commonly prescribed to treat patients with type 2 diabetes. Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake. At a molecular level, metformin increases AMP-activated protein kinase activity and increases antioxidant protection, resulting in reductions in both oxidative damage accumulation and chronic inflammation. Our results indicate that these actions may contribute to the beneficial effects of metformin on healthspan and lifespan. These findings are in agreement with current epidemiological data and raise the possibility of metformin-based interventions to promote healthy aging.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Antioxidants / pharmacology
  • Biomarkers / blood
  • Caloric Restriction
  • Electron Transport / drug effects
  • Enzyme Activation / drug effects
  • Health*
  • Inflammation / blood
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Longevity / drug effects*
  • Male
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Survival Analysis
  • Transcriptome / drug effects
  • Transcriptome / genetics

Substances

  • Antioxidants
  • Biomarkers
  • Metformin
  • AMP-Activated Protein Kinases

Associated data

  • GEO/GSE40936