Abstract
It has been reported that several aspects of human health could be disturbed during a long-term isolated environment (for instance, the Mars-500 mission), including psychiatric disorders, circadian disruption, temporal dynamics of gut microbiota, immune responses, and physical-activity-related neuromuscular performance. Nevertheless, the mechanisms underlying these disturbances and the interactions among different aspects of human adaptation to extreme environments remain to be elucidated. Epigenetic features, like DNA methylation, might be a linking mechanism that explains the involvement of environmental factors between the human genome and the outcome of health. We conducted an exploration of personalized longitudinal DNA methylation patterns of the peripheral whole blood cells, profiling six subjects across six sampling points in the Mars-500 mission. Specifically, we developed a Personalized Epigenetic-Phenotype Synchronization Analysis (PeSa) algorithm to explore glucose- and mood-state-synchronized DNA methylation sites, focusing on finding the dynamic associations between epigenetic patterns and phenotypes in each individual, and exploring the underling epigenetic connections between glucose and mood-state disturbance. Results showed that DMPs (differentially methylated-probes) were significantly enriched in pathways related to glucose metabolism (Type II diabetes mellitus pathway), mood state (Long-term depression) and circadian rhythm (Circadian entrainment pathway) during the mission. Furthermore, our data revealed individualized glucose-synchronized and mood-state-synchronized DNA methylation sites, and PTPRN2 was found to be associated with both glucose and mood state disturbances across all six subjects. Our findings suggest that personalized phenotype-synchronized epigenetic features could reflect the effects on the human body, including the disturbances of glucose and mood-states. The association analysis of DNA methylation and phenotypes, like the PeSa analysis, could provide new possibilities in understanding the intrinsic relationship between phenotypic changes of the human body adapting to long-term isolation environmental factors.
Highlights
Adaptation to an extreme environment such as long-term isolation during a human spaceflight, represents a formidable medical challenge, but it provides a unique platform for investigating human adaptation to extreme environmental changes
Multiple sampling points correspondingly synchronized with DNA methylation profiling were assigned to characterize three categories of parameters related to nutrient metabolism, stress and immunology (10 sampling points, covering six sampling points of DNA methylation profiling)
While previous analyses of data in the Mars500 experiment have reported insights of psychiatric disorders (Wang et al, 2014), circadian disruptions (Basner et al, 2013), temporal dynamics of gut microbiota (Turroni et al, 2017), immune responses (Yi B. et al, 2014), and physical-activityrelated neuromuscular performance (Belavy et al, 2013), this study was focused on individualized high frequency sampling for epigenetic profiling across the mission, and exploring the dynamic linking between DNA methylation changes and different aspect of phenotypes (POMS-Total Mood Disturbance (TMD) for mood-state, and glucose for metabolism)
Summary
Adaptation to an extreme environment such as long-term isolation during a human spaceflight, represents a formidable medical challenge, but it provides a unique platform for investigating human adaptation to extreme environmental changes. Since the association between genome-wide DNA methylation and phenotype has been reported in population cohorts (Rakyan et al, 2011; Petersen et al, 2014; Doostparast Torshizi and Fazel Zarandi, 2015), twins studies (Martino et al, 2013; Jaskowiak et al, 2014; Yi H. et al, 2014) and cell studies (Lorthongpanich et al, 2013; Ziller et al, 2013; Wang and Pan, 2014)_ENREF_10, DNA methylation might be a linking mechanism which explains the involvement of environmental factors between the human genome and health outcomes. It is reasonable to hypothesize that epigenetic profiles (like DNA methylation) could drift during longitudinal confinement during the Mars 500 mission, and the DNA methylation change could be associated with different aspects of phenotype variations (such as physiological and psychological regulation)
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