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Metformin's Impact on Aging and Longevity Through DNA Methylation

02-22-2023

“In this study, we compared genome-wide DNA methylation rates among metformin users and nonusers [...]”

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BUFFALO, NY- February 22, 2023 – A new research paper was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 15, Issue 3, entitled, “Metformin use history and genome-wide DNA methylation profile: potential molecular mechanism for aging and longevity.”

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. 

In this recent study, researchers Pedro S. Marra, Takehiko Yamanashi, Kaitlyn J. Crutchley, Nadia E. Wahba, Zoe-Ella M. Anderson, Manisha Modukuri, Gloria Chang, Tammy Tran, Masaaki Iwata, Hyunkeun Ryan Cho, and Gen Shinozaki from Stanford University School of Medicine, University of Iowa, Tottori University Faculty of Medicine, University of Nebraska Medical Center College of Medicine, and Oregon Health and Science University School of Medicine hypothesized that metformin’s potential mechanism of action for longevity is through its epigenetic modifications.

“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.”

The researchers 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. 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. They 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).

“This study may elucidate metformin’s potential role in longevity through epigenetic modifications and other possible mechanisms of action.”

Read the Full Paper: DOI: https://doi.org/10.18632/aging.204498 

Corresponding Author: Gen Shinozaki

Corresponding Email: gens@stanford.edu 

Keywords: metformin, longevity, diabetes, epigenetics, aging, inflammation, methylation

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About Aging-US:

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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