Metformin use history and genome-wide DNA methylation profile: potential molecular mechanism for aging and longevity

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; Gen Shinozaki

doi:10.18632/aging.204498

Back

Journal article

Open access

Metformin use history and genome-wide DNA methylation profile: potential molecular mechanism for aging and longevity

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, …

Aging (Albany, NY.), Vol.15(3), pp.601-616

02/02/2023

DOI: 10.18632/aging.204498

PMCID: PMC9970305

PMID: 36734879

Files and links (1)

url

https://doi.org/10.18632/aging.204498View

Published (Version of record) Open Access

Abstract

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. 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. 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 ( < 5E-08). This study may elucidate metformin's potential role in longevity through epigenetic modifications and other possible mechanisms of action.

Aging

Diabetes

Epigenetics

Inflammation

methylation

longevity

metformin

Details

Title: Subtitle: Metformin use history and genome-wide DNA methylation profile: potential molecular mechanism for aging and longevity
Creators: Pedro S Marra - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Takehiko Yamanashi - Tottori University
Kaitlyn J Crutchley - University of Nebraska Medical Center
Nadia E Wahba - Department of Psychiatry, Oregon Health and Science University School of Medicine, Portland, OR 97239, USA
Zoe-Ella M Anderson - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Manisha Modukuri - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Gloria Chang - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Tammy Tran - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Masaaki Iwata - Tottori University
Hyunkeun Ryan Cho - University of Iowa
Gen Shinozaki - University of Iowa
Resource Type: Journal article
Publication Details: Aging (Albany, NY.), Vol.15(3), pp.601-616
DOI: 10.18632/aging.204498
PMID: 36734879
PMCID: PMC9970305
NLM abbreviation: Aging (Albany NY)
eISSN: 1945-4589
Language: English
Date published: 02/02/2023
Academic Unit: Psychiatry; Biostatistics; Neurosurgery
Record Identifier: 9984365159502771

Metrics

14 Record Views

13 Times Cited - Web of Science

See more details