Metformin improves healthspan and lifespan in mice

被引:0
作者
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
Rafael de Cabo
机构
[1] Translational Gerontology Branch,Department of Biochemistry
[2] National Institute on Aging,Department of Genetics
[3] National Institutes of Health,Department of Medicine and Oncology
[4] Kolling Institute of Medical Research,Department of Pathology
[5] Royal North Shore Hospital,undefined
[6] Sydney Medical School,undefined
[7] University of Sydney,undefined
[8] University of California Riverside,undefined
[9] Laboratory of Molecular Gerontology,undefined
[10] National Institute on Aging,undefined
[11] National Institutes of Health,undefined
[12] Paul F. Glenn Laboratories for the Biological Mechanisms of Aging,undefined
[13] Harvard Medical School,undefined
[14] McGill University,undefined
[15] Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology,undefined
[16] Stuttgart and University of Tübingen,undefined
[17] Gene Expression and Genomics Unit,undefined
[18] National Institute on Aging,undefined
[19] National Institutes of Health,undefined
[20] Laboratory of Epidemiology,undefined
[21] Demography and Biometry,undefined
[22] National Institute on Aging,undefined
[23] Nutritional Neuroscience and Aging Laboratory,undefined
[24] Pennington Biomedical Research Center,undefined
[25] Louisiana State University System,undefined
[26] University of Washington,undefined
来源
Nature Communications | / 4卷
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摘要
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.
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