Abstract
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.
Highlights
Selective pressures resulting from environmental conditions modify the rate of aging and are hypothesized to contribute to variation in lifespan across species [1]
We examined the genomic locations of the age-associated cytosines, as determined by Spearman correlation coefficients, with respect to their proximity to CpG islands and genic context
As CpGs in the human epigenetic clock are reported to co-localize with glucocorticoid response elements [29], we tested for significant deviations from the expected overlap between age-associated sites and three hormone response elements
Summary
Selective pressures resulting from environmental conditions modify the rate of aging and are hypothesized to contribute to variation in lifespan across species [1]. Variation in the rate of aging reflects a decoupling of biological from chronological aging which may underlie variable timing of life history events, physiological function, and the onset of age-related disease [2, 3]. The mechanisms by which the environment contributes to variation in biological aging are not fully resolved. Is variation in the DNA methylome linked to extrinsic factors such as exposure to contaminants [6], famine [7], season [8] and social environment [9], recent studies show compelling links between epigenetic changes and aging [2, 10, 11]. Additional research on the basic biology of epigenetic aging in a variety of species is needed to advance a broader understanding of the underlying mechanisms driving both normal and accelerated epigenetic aging
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
