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 |
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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 |
format | Article |
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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.</description><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms3192</identifier><identifier>PMID: 23900241</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>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</subject><ispartof>Nature communications, 2013-07, Vol.4 (1), p.2192-9</ispartof><rights>Springer Nature Limited 2013</rights><rights>Copyright Nature Publishing Group Jul 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-p255t-19073ddca1692ef9765af5354cb79d5563a8fd6a12d25ef275fb3bc2f92d7fab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736576/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736576/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/ncomms3192$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23900241$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martin-Montalvo, Alejandro</creatorcontrib><creatorcontrib>Mercken, Evi M.</creatorcontrib><creatorcontrib>Mitchell, Sarah J.</creatorcontrib><creatorcontrib>Palacios, Hector H.</creatorcontrib><creatorcontrib>Mote, Patricia L.</creatorcontrib><creatorcontrib>Scheibye-Knudsen, Morten</creatorcontrib><creatorcontrib>Gomes, Ana P.</creatorcontrib><creatorcontrib>Ward, Theresa M.</creatorcontrib><creatorcontrib>Minor, Robin K.</creatorcontrib><creatorcontrib>Blouin, Marie-José</creatorcontrib><creatorcontrib>Schwab, Matthias</creatorcontrib><creatorcontrib>Pollak, Michael</creatorcontrib><creatorcontrib>Zhang, Yongqing</creatorcontrib><creatorcontrib>Yu, Yinbing</creatorcontrib><creatorcontrib>Becker, Kevin G.</creatorcontrib><creatorcontrib>Bohr, Vilhelm A.</creatorcontrib><creatorcontrib>Ingram, Donald K.</creatorcontrib><creatorcontrib>Sinclair, David A.</creatorcontrib><creatorcontrib>Wolf, Norman S.</creatorcontrib><creatorcontrib>Spindler, Stephen R.</creatorcontrib><creatorcontrib>Bernier, Michel</creatorcontrib><creatorcontrib>de Cabo, Rafael</creatorcontrib><title>Metformin improves healthspan and lifespan in mice</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><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.</description><subject>692/308</subject><subject>692/700/565/1436</subject><subject>Aging</subject><subject>AMP</subject><subject>AMP-activated protein kinase</subject><subject>AMP-Activated Protein Kinases</subject><subject>Animals</subject><subject>Antidiabetics</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Biomarkers - blood</subject><subject>Caloric Restriction</subject><subject>Cardiovascular disease</subject><subject>Cholesterol</subject><subject>Damage accumulation</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Drug dosages</subject><subject>Electron Transport - drug effects</subject><subject>Enzyme Activation - drug effects</subject><subject>Epidemiology</subject><subject>Gene expression</subject><subject>Gerontology</subject><subject>Health</subject><subject>Health promotion</subject><subject>Humanities and Social Sciences</subject><subject>Inflammation - blood</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - pathology</subject><subject>Insulin</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Life span</subject><subject>Longevity - drug effects</subject><subject>Male</subject><subject>Metabolic syndrome</subject><subject>Metformin</subject><subject>Metformin - pharmacology</subject><subject>Metformin - therapeutic use</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>multidisciplinary</subject><subject>Nutrient deficiency</subject><subject>Proteins</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Survival Analysis</subject><subject>Transcriptome 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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23900241</pmid><doi>10.1038/ncomms3192</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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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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