Metformin improves healthspan and lifespan in mice

By A. Martín-Montalvo, E. Mercken, S. Mitchell, Hector H. Palacios, P. Mote, M. Scheibye-Knudsen, A. P. Gomes, Theresa M. Ward, R. Minor, M. Blouin and 12 more. Nature Communications, 2013

1,361 citations recorded by the source corpus.

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.

Subfields: Aging, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/847fd05df7166a2d44d3ab27f2c0d1bde10d490f

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Citations in the corpus

Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019, background): “, by low levels of intracellular adenosine triphosphate (ATP), leading to the extension of healthy lifespan in model organisms (95).”
Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status (2016, positive): “…of BMI and DM. 46 Blockade of CCL11 can suppress aspects of age-related cellular dysfunction, 47 and it is possible that observed effects of metformin on mammalian longevity, 48,49 where suppression of NF-κ B is also observed, 49 may owe at least in part to suppression of this cytokine.”
Metformin as a Tool to Target Aging (2016, positive): “…in these studies, metformin also increased AMPK activity and increased antioxidant protection, resulting in reductions in both chronic inflammation and accumulation of oxidative damage (Martin-Montalvo et al., 2013), all of which may contribute to health span and lifespan seen in animal models.”
Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges (2014, background): “We postulate that increased healthspan of mice on TRF likely reflects better metabolic responses tomobilize energy stores (Martin-Montalvo et al., 2013).”
The mechanisms of action of metformin (2017, background): “It is possible that recent observations, consistent with the ability of metformin to prolong mammalian lifespan [54, 55], may, at”
Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease (2019, background): “Elderly animals had an increased lifespan and healthspan as a result of suppression of inflammation and oxidative damage [184].”
β-Hydroxybutyrate (2017, positive): “Inhibition of the TOR (target of rapamycin) signaling complex by rapamycin (46), activation of AMPK by metformin (81), or provision of NAD+ precursors (161) recapitulates some of the beneficial effects of dietary restriction on diseases of aging and longevity.”