Research Paper Volume 13, Issue 19 pp 22752—22771

Exposure to ionizing radiation disrupts normal epigenetic aging in Japanese medaka

Emily M. Bertucci1,2, , Marilyn W. Mason2, , Olin E. Rhodes1,2, , Benjamin B. Parrott1,2, ,

  • 1 Odum School of Ecology, University of Georgia, Athens, GA 30602, USA
  • 2 Savannah River Ecology Laboratory, University of Georgia, Aiken, SC 29802, USA

Received: April 8, 2021       Accepted: September 3, 2021       Published: October 13, 2021
How to Cite

Copyright: © 2021 Bertucci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Alterations to the epigenome are a hallmark of biological aging and age-dependent patterning of the DNA methylome (“epigenetic aging”) can be modeled to produce epigenetic age predictors. Rates of epigenetic aging vary amongst individuals and correlate to the onset of age-related disease and all-cause mortality. Yet, the origins of epigenetic-to-chronological age discordance are not empirically resolved. Here, we investigate the relationship between aging, DNA methylation, and environmental exposures in Japanese medaka (Oryzias latipes). We find age-associated DNA methylation patterning enriched in genomic regions of low CpG density and that, similar to mammals, most age-related changes occur during early life. We construct an epigenetic clock capable of predicting chronological age with a mean error of 61.1 days (~8.4% of average lifespan). To test the role of environmental factors in driving epigenetic age variation, we exposed medaka to chronic, environmentally relevant doses of ionizing radiation. Because most organisms share an evolutionary history with ionizing radiation, we hypothesized that exposure would reveal fundamental insights into environment-by-epigenetic aging interactions. Radiation exposure disrupted epigenetic aging by accelerating and decelerating normal age-associated patterning and was most pronounced in cytosines that were moderately associated with age. These findings empirically demonstrate the role of DNA methylation in integrating environmental factors into aging trajectories.


ARE: androgen response element; DMC: differentially methylated cytosine; ERE: estrogen response element; FDR: false discovery rate; GRE: glucocorticoid response element; HRE: hormone response element; IR: ionizing radiation; LoDIF: low dose irradiation facility; PCR: polymerase chain reaction; PDR: percentage of discordant reads.