Metformin improves putative longevity effectors in peripheral mononuclear cells from subjects with prediabetes. A randomized controlled trial
| Autor: | Giulio Ceolotto, S. Vigili de Kreutzenberg, Anna Maria Cattelan, Paolo Garagnani, Vincenzo Borelli, Marta Mazzucato, Angelo Avogaro, Elisa Pagnin, Maria Giulia Bacalini, Claudio Franceschi, Gian Paolo Fadini |
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| Přispěvatelé: | Vigili de Kreutzenberg, S., Ceolotto, G., Cattelan, A., Pagnin, E., Mazzucato, M., Garagnani, P., Borelli, V., Bacalini, M.G., Franceschi, C., Fadini, G.P., Avogaro, A. |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Aging endocrine system diseases Endocrinology Diabetes and Metabolism Medicine (miscellaneous) AMP-Activated Protein Kinases Placebo Peripheral blood mononuclear cell Dysmetabolism Monocytes Prediabetic State Sirtuin 1 Polysaccharides Internal medicine Gene expression medicine Humans Hypoglycemic Agents Prediabetes PI3K/AKT/mTOR pathway Telomere Shortening Inflammation Nutrition and Dietetics Cell Death business.industry TOR Serine-Threonine Kinases AMPK Middle Aged medicine.disease Longevity gene Metformin Endocrinology Ageing Female Insulin Resistance Cardiology and Cardiovascular Medicine business Biomarkers medicine.drug |
| Popis: | Background and aims: Prediabetes increases cardiovascular risk and is associated with excess mortality. In preclinical models, metformin has been shown to exert anti-ageing effects. In this study, we sought to assess whether metformin modulates putative effector longevity pro- grams in prediabetic subjects. Methods and results: In a randomized, single-blind, placebo-controlled trial, 38 prediabetic sub- jects received metformin (1500 mg/day) or placebo for 2 months. At baseline and after treat- ment, we collected anthropometric and metabolic parameters. Gene and protein levels of SIRT1, mTOR, p53, p66Shc, SIRT1 activity, AMPK activation, telomere length, and SIRT1 promoter chromatin accessibility were determined in peripheral blood mononuclear cells (PBMCs). Plasma N-glycans, non-invasive surrogate markers of ageing, were also analysed. Compared to baseline, metformin significantly improved metabolic parameters and insulin sensitivity, increased SIRT1 gene/protein expression and SIRT1 promoter chromatin accessibility, elevated mTOR gene expression with concomitant reduction in p70S6K phosphorylation in sub- jects' PBMCs, and modified the plasma N-glycan profile. Compared to placebo, metformin increased SIRT1 protein expression and reduced p70S6K phosphorylation (a proxy of mTOR ac- tivity). Plasma N-glycans were also favourably modified by metformin compared to placebo. Conclusion: In individuals with prediabetes, metformin ameliorated effector pathways that have been shown to regulate longevity in animal models. ClinicalTrials.gov Identifier: NCT01765946 e January 2013. |
| Databáze: | OpenAIRE |
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