Metformin improves healthspan and lifespan in mice

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, Matthias Schwab, Michael Pollak, Yongqing Zhang, Yinbing Yu, Kevin G. Becker, Vilhelm A. Bohr, Donald K. Ingram, David A. Sinclair, Norman S. Wolf, Stephen R. Spindler, Michel Bernier and Rafael de Cabo ()
Additional contact information
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
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

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3192

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