DNA Methylation Changes Are Associated With an Incremental Ascent to High Altitude

Abstract

Genetic and nongenetic factors are involved in the individual ability to physiologically acclimatize to high-altitude hypoxia through processes that include increased heart rate and ventilation. High-altitude acclimatization is thought to have a genetic component, yet it is unclear if other factors, such as epigenetic gene regulation, are involved in acclimatization to high-altitude hypoxia in nonacclimatized individuals. We collected saliva samples from a group of healthy adults of European ancestry (n = 21) in Kathmandu (1,400 m; baseline) and three altitudes during a trek to the Everest Base Camp: Namche (3,440 m; day 3), Pheriche (4,240 m; day 7), and Gorak Shep (5,160 m; day 10). We used quantitative bisulfite pyrosequencing to determine changes in DNA methylation, a well-studied epigenetic marker, in LINE-1, EPAS1, EPO, PPARa, and RXRa. We found significantly lower DNA methylation between baseline (1,400 m) and high altitudes in LINE-1, EPO (at 4,240 m only), and RXRa. We found increased methylation in EPAS1 (at 4,240 m only) and PPARa. We also found positive associations between EPO methylation and systolic blood pressure and RXRa methylation and hemoglobin. Our results show that incremental exposure to hypoxia can affect the epigenome. Changes to the epigenome, in turn, could underlie the process of altitude acclimatization.

Transcriptomic Changes in Young Japanese Males After Exposure to Acute Hypobaric Hypoxia

“…This suggests that acute hypobaric hypoxic stress did not greatly affect the transcriptome profile of the study subjects, and it may result in no detection of significantly downregulated DEGs. It is possible that peaks of gene expression in response to hypoxia are varied and depend on the duration of hypoxic exposure (Klomp et al, 2020), while human DNA methylation levels, which can regulate gene expression, may be influenced by the severity or the duration of hypoxic exposure (Childebayeva et al, 2019). In addition, we focused on transcriptional changes after acute hypobaric hypoxia exposure but did not assess them during the exposure.…”

The effects of high altitude ascent on splenic contraction and the diving response during voluntary apnoea

“…Some overlap in the participant pool and ancillary cardiorespiratory measures exists with Childebayeva et al. (2019), Leacy et al. (2021) and Lefferts et al.…”

“…Although this study took place as a part of a large expedition to HA in May 2018, the experimental question and design were planned a priori in advance. Some overlap in the participant pool and ancillary cardiorespiratory measures exists with Childebayeva et al (2019), Leacy et al (2021) and Lefferts et al (2019a;2019b).…”

Paternal hypoxia exposure primes offspring for increased hypoxia resistance

“…DNA methylation is known to be altered by hypoxia exposure in fishes (Lai et al, 2019;Wang et al, 2016) and other vertebrates (Childebayeva et al, 2019;Zhang et al, 2017). Thus, we hypothesized that hypoxia might produce changes in the paternal methylome, which are inherited to the offspring, explaining the observed tolerance to acute hypoxia and differential gene expression.…”