Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: A longitudinal study of DNA methylation as a potential mediator of age-related diabetes risk.

Authors: Grant, Crystal D; Jafari, Nadereh; Hou, Lifang; Li, Yun; Stewart, James D; Zhang, Guosheng; Lamichhane, Archana; Manson, JoAnn E; Baccarelli, Andrea A; Whitsel, Eric A; Conneely, Karen N

Published In Geroscience, (2017 12)

Abstract: DNA methylation (DNAm) has been found to show robust and widespread age-related changes across the genome. DNAm profiles from whole blood can be used to predict human aging rates with great accuracy. We sought to test whether DNAm-based predictions of age are related to phenotypes associated with type 2 diabetes (T2D), with the goal of identifying risk factors potentially mediated by DNAm. Our participants were 43 women enrolled in the Women's Health Initiative. We obtained methylation data via the Illumina 450K Methylation array on whole blood samples from participants at three timepoints, covering on average 16 years per participant. We employed the method and software of Horvath, which uses DNAm at 353 CpGs to form a DNAm-based estimate of chronological age. We then calculated the epigenetic age acceleration, or Δage, at each timepoint. We fit linear mixed models to characterize how Δage contributed to a longitudinal model of aging and diabetes-related phenotypes and risk factors. For most participants, Δage remained constant, indicating that age acceleration is generally stable over time. We found that Δage associated with body mass index (p = 0.0012), waist circumference (p = 0.033), and fasting glucose (p = 0.0073), with the relationship with BMI maintaining significance after correction for multiple testing. Replication in a larger cohort of 157 WHI participants spanning 3 years was unsuccessful, possibly due to the shorter time frame covered. Our results suggest that DNAm has the potential to act as a mediator between aging and diabetes-related phenotypes, or alternatively, may serve as a biomarker of these phenotypes.

PubMed ID: 29159506 Exiting the NIEHS site

MeSH Terms: Age Distribution; Aged; Aging/genetics*; Aging/physiology; Body Mass Index; DNA Methylation*; Diabetes Mellitus, Type 2/epidemiology; Diabetes Mellitus, Type 2/genetics*; Diabetes Mellitus, Type 2/physiopathology; Epigenesis, Genetic*; Female; Genome-Wide Association Study; Humans; Longitudinal Studies; Middle Aged; Predictive Value of Tests; Prevalence; Risk Assessment; United States

Back
to Top