The aging DNA methylome reveals environment-by-aging interactions in a model teleost

Abstract

The rate at which individuals age underlies variation in life history and attendant health and disease trajectories. Age specific patterning of the DNA methylome (epigenetic aging) is strongly correlated with chronological age in humans and can be modeled to produce epigenetic age predictors. However, epigenetic age estimates vary among individuals of the same age, and this mismatch is correlated to the onset of age-related disease and all-cause mortality. Yet, the origins of epigenetic-to-chronological age discordance are not resolved. In an effort to develop a tractable model in which environmental drivers of epigenetic aging can be assessed, we investigate the relationship between aging and DNA methylation in a small teleost, medaka (Oryzias latipes). We find that age-associated DNA methylation patterning occurs broadly across the genome, with the majority of age-related changes occurring during early life. By modeling the stereotypical nature of age-associated DNA methylation dynamics, we built an epigenetic clock, which predicts chronological age with a mean error of 29.1 days (~4% of average lifespan). Characterization of clock loci suggests that aspects of epigenetic aging are functionally similar across vertebrates. To understand how environmental factors interact with epigenetic aging, we exposed medaka to four doses of ionizing radiation for seven weeks, hypothesizing that exposure to such an environmental stressor would accelerate epigenetic aging. While the epigenetic clock was not significantly affected, radiation exposure accelerated and decelerated patterns of normal epigenetic aging, with radiation-induced epigenetic alterations enriched at loci that become hypermethylated with age. Together, our findings advance ongoing research attempting to elucidate the functional role of DNA methylation in integrating environmental factors into the rate of biological aging.

Age prediction of green turtles with an epigenetic clock

“…Mammals have been the primary focus of the development of epigenetic clocks (Lu et al, 2021; De Paoli‐Iseppi et al, 2017). Although there has been a recent increase in the development of epigenetic clocks for fishes, the largest vertebrate class, and birds (Anastasiadi & Piferrer, 2020; Bertucci et al, 2021; Mayne, Korbie, et al, 2020). This study is the first to develop an epigenetic clock for reptiles.…”

Development of DNA methylation-based epigenetic age predictors in loblolly pine (Pinus taeda)

“…amplicon sequencing, bait capture techniques) are likely needed if measures of epigenetic age are to be scaled to stand and population applications (Meek & Larson, 2019). Due to the age distributions of our sampled trees, age predictions for our individuals older than 55 years of age were poor, which may have contributed to the greater MAE from our clocks compared to those predicting ages for many vertebrate species (Bertucci et al, 2021;Bors et al, 2021;Lemaître et al, 2020;Meer, Podolskiy, Tyshkovskiy, & Gladyshev, 2018;Stubbs et al, 2017). As we initially removed sites not present in at least 80% of our individuals and many of our trees were within stand ages (Cunningham, n.d.;Li et al, 1999;Stiff & Stansfield, 2003), additional sampling of older trees could allow for retention of higher numbers of cytosine sites whose methylation status remains dynamic in later life, allowing for more accurate age predictions of older trees in further clock studies.…”

“…In one of the first DNA methylation-based age predictors or "epigenetic clocks" developed by Horvath (2013), the methylation status of 353 cytosines predicts human chronological age with an error of ± 3.6 years. Epigenetic clocks have subsequently been developed in a variety of other mammalian (Horvath, 2013;Weidner et al, 2014), avian (Raddatz et al, 2021), and fish species (Anastasiadi & Piferrer, 2020;Bertucci, Mason, Rhodes, & Parrott, 2021;Mayne et al, 2020), and are currently being applied to biomedical and conservation problems, as well to questions regarding their relationship to the underlying biology of aging and senescence (Bertucci & Parrott, 2020;Kabacik, Horvath, Cohen, & Raj, 2018). However, whereas the phenomenon of epigenetic aging appears to be a conserved aspect of biological aging in vertebrates, age-associated changes to DNA methylation and their ability to predict chronological age in plants is relatively unexplored (Parrott & Bertucci, 2019).…”

SARS-CoV-2 Spike and Telomerase RNAs Compared to Arrive at an Explanation for Increased Ageing in Alveolar Cells in Severe COVID-19

“…The ability to go from AEC2 to AEC1 is in need of telomerase (viz. Parra,10). We note that human AEC2 has ACE2 receptors so AEC2 is vulnerable to SARS-CoV-2 infection (viz.…”

“…Note e.g. also in early life, length of telomeres is dynamic 10 and e.g. telomere reduction in skin cells is caused by UV radiation 11 .…”