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Metformin improves healthspan and lifespan in mice

Author

Listed:
  • Alejandro Martin-Montalvo

    (Translational Gerontology Branch, National Institute on Aging, National Institutes of Health)

  • Evi M. Mercken

    (Translational Gerontology Branch, National Institute on Aging, National Institutes of Health)

  • Sarah J. Mitchell

    (Translational Gerontology Branch, National Institute on Aging, National Institutes of Health
    Kolling Institute of Medical Research, Royal North Shore Hospital
    Sydney Medical School, University of Sydney)

  • Hector H. Palacios

    (Translational Gerontology Branch, National Institute on Aging, National Institutes of Health)

  • Patricia L. Mote

    (University of California Riverside)

  • Morten Scheibye-Knudsen

    (Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health)

  • Ana P. Gomes

    (Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School)

  • Theresa M. Ward

    (Translational Gerontology Branch, National Institute on Aging, National Institutes of Health)

  • Robin K. Minor

    (Translational Gerontology Branch, National Institute on Aging, National Institutes of Health)

  • Marie-José Blouin

    (McGill University)

  • Matthias Schwab

    (Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tübingen)

  • Michael Pollak

    (McGill University)

  • Yongqing Zhang

    (Gene Expression and Genomics Unit, National Institute on Aging, National Institutes of Health)

  • Yinbing Yu

    (Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging)

  • Kevin G. Becker

    (Gene Expression and Genomics Unit, National Institute on Aging, National Institutes of Health)

  • Vilhelm A. Bohr

    (Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health)

  • Donald K. Ingram

    (Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research Center, Louisiana State University System)

  • David A. Sinclair

    (Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School)

  • Norman S. Wolf

    (University of Washington)

  • Stephen R. Spindler

    (University of California Riverside)

  • Michel Bernier

    (Translational Gerontology Branch, National Institute on Aging, National Institutes of Health)

  • Rafael de Cabo

    (Translational Gerontology Branch, National Institute on Aging, National Institutes of Health)

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.

Suggested Citation

  • Alejandro Martin-Montalvo & Evi M. Mercken & Sarah J. Mitchell & Hector H. Palacios & Patricia L. Mote & Morten Scheibye-Knudsen & Ana P. Gomes & Theresa M. Ward & Robin K. Minor & Marie-José Blouin &, 2013. "Metformin improves healthspan and lifespan in mice," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
  • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3192
    DOI: 10.1038/ncomms3192
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    Cited by:

    1. Debonneuil, Edouard & Loisel, Stéphane & Planchet, Frédéric, 2018. "Do actuaries believe in longevity deceleration?," Insurance: Mathematics and Economics, Elsevier, vol. 78(C), pages 325-338.
    2. Juewon Kim & Yunju Jo & Donghyun Cho & Dongryeol Ryu, 2022. "L-threonine promotes healthspan by expediting ferritin-dependent ferroptosis inhibition in C. elegans," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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