In vitro relationships of galactic cosmic radiation and epigenetic clocks in human bronchial epithelial cells

Abstract

Ionizing radiation is a well-appreciated health risk, precipitant of DNA damage, and contributor to DNA methylation variability. Nevertheless, relationships of ionizing radiation with DNA methylation-based markers of biological age (i.e. epigenetic clocks) remain poorly understood. Using existing data from human bronchial epithelial cells, we examined in vitro relationships of three epigenetic clock measures (Horvath DNAmAge, MiAge, and epiTOC2) with galactic cosmic radiation (GCR), which is particularly hazardous due to its high linear energy transfer (LET) heavy-ion components. High-LET 56Fe was significantly associated with accelerations in epiTOC2 (β = 192 cell divisions, 95% CI: 71, 313, p-value = .003). We also observed a significant, positive interaction of 56Fe ions and time-in-culture with epiTOC2 (95% CI: 42, 441, p-value = .019). However, only the direct 56Fe ion association remained statistically significant after adjusting for multiple hypothesis testing. Epigenetic clocks were not significantly associated with high-LET 28Si and low-LET X-rays.Our results demonstrate sensitivities of specific epigenetic clock measures to certain forms of GCR. These findings suggest that epigenetic clocks may have some utility for monitoring and better understanding the health impacts of GCR.

Chromosomal positioning and epigenetic architecture influence DNA methylation patterns triggered by galactic cosmic radiation

“…Additionally, the researchers showed acute radiation-induced methylation changes which persisted over time with heritable imprint across epigenome. These findings where further investigated by Nwanaji-Enwerem et al 7 showing that 56 Fe exposure was associated with accelerations in epiTOC2 epigenetic clock suggesting that DNA methylation may be a sensitive biomarker of high-LET 56 Fe ion exposure.…”

Chromosomal positioning and epigenetic architecture influence DNA methylation patterns triggered by galactic cosmic radiation

“…Additionally, the researchers showed acute radiation-induced methylation changes which persisted over time with heritable imprint across epigenome. These ndings where further investigated by Nwanaji-Enwerem et al [7] showing that 56 Fe exposure was associated with accelerations in epiTOC2 epigenetic clock suggesting that DNA methylation may be a sensitive biomarker of high-LET 56 Fe ion exposure.…”

Organs in orbit: how tissue chip technology benefits from microgravity, a perspective

“…Also, in-space facilities have strict loading capacity and experimental limitations, perhaps leading to oversimplification, and therefore inaccuracy, of the tissue chip models on board ( Mu et al, 2022b ; Ferranti et al, 2020b ). In addition, cosmic radiation may greatly impact the efficacy of these tissue chips ( Li et al, 2018 ; Nwanaji-Enwerem et al, 2022 ; Soucy et al, 2011 ; Belli et al, 2002 ). Perhaps protective apparati could be developed to mitigate the exposure to this radiation, or at the very least attenuate it to a lesser degree.…”