Metformin improves healthspan and lifespan in mice

被引:1161
作者
Martin-Montalvo, Alejandro [1 ]
Mercken, Evi M. [1 ]
Mitchell, Sarah J. [1 ,2 ,3 ]
Palacios, Hector H. [1 ]
Mote, Patricia L. [4 ]
Scheibye-Knudsen, Morten [5 ]
Gomes, Ana P. [6 ]
Ward, Theresa M. [1 ]
Minor, Robin K. [1 ]
Blouin, Marie-Jose [7 ]
Schwab, Matthias [8 ,9 ]
Pollak, Michael [7 ]
Zhang, Yongqing [10 ]
Yu, Yinbing [11 ]
Becker, Kevin G. [10 ]
Bohr, Vilhelm A. [5 ]
Ingram, Donald K. [12 ]
Sinclair, David A. [6 ]
Wolf, Norman S. [13 ]
Spindler, Stephen R. [4 ]
Bernier, Michel [1 ]
de Cabo, Rafael [1 ]
机构
[1] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA
[2] Royal N Shore Hosp, Kolling Inst Med Res, St Leonards, NSW 2065, Australia
[3] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia
[4] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA
[5] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA
[6] Harvard Univ, Sch Med, Dept Genet, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA
[7] McGill Univ, Dept Med & Oncol, Montreal, PQ H3A 2B3, Canada
[8] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany
[9] Univ Tubingen, D-70376 Stuttgart, Germany
[10] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA
[11] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA
[12] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA
[13] Univ Washington, Dept Pathol, Seattle, WA 98195 USA
基金
英国医学研究理事会;
关键词
ANTIDIABETIC DRUG METFORMIN; ACTIVATED PROTEIN-KINASE; OXIDATIVE STRESS; HEPATIC GLUCONEOGENESIS; DIETARY RESTRICTION; DNA-DAMAGE; COMPLEX I; RESPIRATION; AMPK; CANCER;
D O I
10.1038/ncomms3192
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
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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页数:9
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