Metformin Use History and Genome-Wide DNA Methylation Profile



February 19, 2023

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  • Aging-US published this research paper in Volume 15, Issue 3, entitled, "Metformin use history and genome-wide DNA methylation profile: potential molecular mechanism for aging and longevity" by researchers from the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA; Department of Neuropsychiatry, Tottori University Faculty of Medicine, Yonago-shi, Tottori, Japan; University of Nebraska Medical Center College of Medicine, Omaha, NE; Department of Psychiatry, Oregon Health and Science University School of Medicine, Portland, OR; Department of Biostatistics, University of Iowa College of Public Health, Iowa City, IA. DOI - Corresponding author - Gen Shinozaki - Abstract Background: Metformin, a commonly prescribed anti-diabetic medication, has repeatedly been shown to hinder aging in pre-clinical models and to be associated with lower mortality for humans. It is, however, not well understood how metformin can potentially prolong lifespan from a biological standpoint. We hypothesized that metformin’s potential mechanism of action for longevity is through its epigenetic modifications. Methods: To test our hypothesis, we conducted a post-hoc analysis of available genome-wide DNA methylation (DNAm) data obtained from whole blood collected from inpatients with and without a history of metformin use. We assessed the methylation profile of 171 patients (first run) and only among 63 diabetic patients (second run) and compared the DNAm rates between metformin users and nonusers. Results: Enrichment analysis from the Kyoto Encyclopedia of Genes and Genome (KEGG) showed pathways relevant to metformin’s mechanism of action, such as longevity, AMPK, and inflammatory pathways. We also identified several pathways related to delirium whose risk factor is aging. Moreover, top hits from the Gene Ontology (GO) included HIF-1α pathways. However, no individual CpG site showed genome-wide statistical significance (p < 5E-08). Conclusion: This study may elucidate metformin’s potential role in longevity through epigenetic modifications and other possible mechanisms of action. Sign up for free Altmetric alerts about this article - Keywords - metformin, longevity, diabetes, epigenetics, aging, inflammation, methylation About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at​​ and connect with us: SoundCloud - Facebook - Twitter - Instagram - YouTube -​ LinkedIn - Pinterest - Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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