Metformin improves healthspan and lifespan in mice

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...

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Veröffentlicht in:Nature communications 2013-07, Vol.4 (1), p.2192-9
Hauptverfasser: Martin-Montalvo, Alejandro, Mercken, Evi M., Mitchell, Sarah J., Palacios, Hector H., Mote, Patricia L., Scheibye-Knudsen, Morten, Gomes, Ana P., Ward, Theresa M., Minor, Robin K., Blouin, Marie-José, Schwab, Matthias, Pollak, Michael, Zhang, Yongqing, Yu, Yinbing, Becker, Kevin G., Bohr, Vilhelm A., Ingram, Donald K., Sinclair, David A., Wolf, Norman S., Spindler, Stephen R., Bernier, Michel, de Cabo, Rafael
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container_issue 1
container_start_page 2192
container_title Nature communications
container_volume 4
creator Martin-Montalvo, Alejandro
Mercken, Evi M.
Mitchell, Sarah J.
Palacios, Hector H.
Mote, Patricia L.
Scheibye-Knudsen, Morten
Gomes, Ana P.
Ward, Theresa M.
Minor, Robin K.
Blouin, Marie-José
Schwab, Matthias
Pollak, Michael
Zhang, Yongqing
Yu, Yinbing
Becker, Kevin G.
Bohr, Vilhelm A.
Ingram, Donald K.
Sinclair, David A.
Wolf, Norman S.
Spindler, Stephen R.
Bernier, Michel
de Cabo, Rafael
description 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. The anti-diabetic drug metformin has been shown to increase lifespan of some model organisms, but results have been conflicting. Here, Martin-Montalvo et al . administer one of two doses of metformin to male mice and show that the lower dose increases healthspan and lifespan, while the higher dose is toxic.
doi_str_mv 10.1038/ncomms3192
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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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subjects 692/308
692/700/565/1436
Aging
AMP
AMP-activated protein kinase
AMP-Activated Protein Kinases
Animals
Antidiabetics
Antioxidants
Antioxidants - pharmacology
Biomarkers - blood
Caloric Restriction
Cardiovascular disease
Cholesterol
Damage accumulation
Diabetes
Diabetes mellitus (non-insulin dependent)
Drug dosages
Electron Transport - drug effects
Enzyme Activation - drug effects
Epidemiology
Gene expression
Gerontology
Health
Health promotion
Humanities and Social Sciences
Inflammation - blood
Inflammation - drug therapy
Inflammation - pathology
Insulin
Kinases
Laboratories
Life span
Longevity - drug effects
Male
Metabolic syndrome
Metformin
Metformin - pharmacology
Metformin - therapeutic use
Mice
Mice, Inbred C57BL
Mitochondria - drug effects
Mitochondria - metabolism
multidisciplinary
Nutrient deficiency
Proteins
Science
Science (multidisciplinary)
Survival Analysis
Transcriptome - drug effects
Transcriptome - genetics
title Metformin improves healthspan and lifespan in mice
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