Correlation of DNA methylation patterns to the phenotypic features of Tibetan elite alpinists in extreme hypoxia

Zhuoma, Basang; Zhang, Shixuan; La, Yang; Deji, Quzong; Li, Yang; Ma, Yanyun; Meng, Hao; Pu, Weilin; Liu, Xiaoyu; Xie, Hongjun; Liang, Meng; Wang, Jiucun; Qiangba, Danzeng

doi:10.1016/j.jgg.2021.05.015

Cited by 7 publications

(8 citation statements)

References 42 publications

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“…However, keeping in mind that NOP has the capacity to mimic hypoxia [25,36,44] and is therefore a powerful tool to trigger a hormetic response, it may be used as a reason-able hypothesis to suggests that the lower the hyperoxia delta, the longer the permissive oxidative state, allowing the secondary cellular messengers [45] to potentiate their nuclear transcription role and trigger a strong and rapid response (within the first 3 h). Indeed, recent data demonstrate epigenic changes by methylation/demethylation upon gene expression are related to oxygen homeostasis [46]. The kinetics of these oxygen-induced activation/deactivation mechanisms are dependent upon enzymatic reactions where the role of 2-oxoglutarate dioxygenase seems to be decisive [47].…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress Response’s Kinetics after 60 Minutes at Different (30% or 100%) Normobaric Hyperoxia Exposures

Leveque

Mrakic‐Sposta

Lafère

et al. 2022

IJMS

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Oxygen is a powerful trigger for cellular reactions and is used in many pathologies, including oxidative stress. However, the effects of oxygen over time and at different partial pressures remain poorly understood. In this study, the metabolic responses of normobaric oxygen intake for 1 h to mild (30%) and high (100%) inspired fractions were investigated. Fourteen healthy non-smoking subjects (7 males and 7 females; age: 29.9 ± 11.1 years, height: 168.2 ± 9.37 cm; weight: 64.4 ± 12.3 kg; BMI: 22.7 ± 4.1) were randomly assigned in the two groups. Blood samples were taken before the intake at 30 min, 2 h, 8 h, 24 h, and 48 h after the single oxygen exposure. The level of oxidation was evaluated by the rate of reactive oxygen species (ROS) and the levels of isoprostane. Antioxidant reactions were observed by total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT). The inflammatory response was measured using interleukin-6 (IL-6), neopterin, creatinine, and urates. Oxidation markers increased from 30 min on to reach a peak at 8 h. From 8 h post intake, the markers of inflammation took over, and more significantly with 100% than with 30%. This study suggests a biphasic response over time characterized by an initial “permissive oxidation” followed by increased inflammation. The antioxidant protection system seems not to be the leading actor in the first place. The kinetics of enzymatic reactions need to be better studied to establish therapeutic, training, or rehabilitation protocols aiming at a more targeted use of oxygen.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress Response’s Kinetics after 60 Minutes at Different (30% or 100%) Normobaric Hyperoxia Exposures

Leveque

Mrakic‐Sposta

Lafère

et al. 2022

IJMS

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“…Genome-scale DNA methylation was measured in blood samples of 64 Tibetans 22 , and we assessed the methylation status of approximately 741,489 CpG sites. We used Methylation Gene Base analyses (MGBA) and OLS to explore the effect of changes in Climbing age (CA, the number of summits at 8848m) on CpGs methylation, adjusted for age and BMI and the extent of immune in ltration.…”

Section: Characteristics Of the Variation Of Cpg Under Seh Perturbationmentioning

confidence: 99%

“…The adaptive regulation of homeostasis can effectively inhibit the stress response induced by the external environment 19 , thus reducing the physiological burden of the body 20 , such as the adaptation of the immune system 21 . Our previous study suggested that upon extreme exposure, physiological phenotypic states are affected by methylation of CpGs in genes such as PTEN and PPP1R13L 22 . In addition, studies on methylation in the LINE-1 and EPAS1 genes in Andean, Tibetan, and Ethiopian populations similarly suggest environmental adaptations at high altitudes 23 .…”

Section: Introductionmentioning

confidence: 99%

Superposition extreme high-altitude exposure (8848m) forms episodic memory of LIPN and PLCH1 genes associated

Zhang

Duoji

et al. 2023

Preprint

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Background: Extreme environmental stress interactions with DNA methylation may produce episodic memory for environmental adaptation. Methods: In the present study, 64 volunteers born and living at an altitude of 4,700 m were recruited, including 32 volunteers who were repeatedly exposed to high altitudes (up to 8,848 m, up to 11 times). We explored the changes in the genes hosting 741,489 CpG loci as well as 39 physiological phenotypes under superposition extreme high-altitude exposure (SEH). Results: 13 CpG for 11 genes were identified with tightly linked networks to five phenotypes. Bayesian causal network analysis suggests network properties of 15 SEH-related phenotypic networks and MP-SSN, reflected in increased robustness with an increasing number of SEH exposures, suggesting environmental resistance. In addition, we explored the characteristics under SEH of the MP-SSN network nodes in populations with significant differences in SpO2 (n High-adaptability= 28; n Low-adaptability= 36) and found concomitant changes in five phenotypes and CpG methylation, while the changes occurred earlier in the high SpO2 population (Climbing age = 5 times). Conclusion: Considering evidence from the literature and database validation, we suggest that the promoter and enhancer regions of the LIPN and PLCH1 genes may be influenced by methylation memory generated by light environment exposure during SEH exposure. Methylation memory may have an effect on the phenotype by influencing the action of the pathway in which the gene is located, thus advancing the environmental adaptation status of SEH, such as SpO2 and SP.

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“…Epigenetics seems to play a significant role in exercise and extreme environments [11]. Recently, it was shown that external stressors could indeed interact with the genome, especially when changes in the oxygen partial pressure are involved [16]. This is may not be all that surprising as we know that physical exercise can produce extensive cellular reactions, including epigenetic reactions.…”

Section: Epigenetics and The Challenge Of Cellular Responsesmentioning

confidence: 99%

“…Recent data showed an epigenetic change through methylation in alpinists exposed to hypoxia, demonstrating rapid changes that were even recently not considered possible in the human epigenome following acute oxygen variation [16].…”

Section: Epigenetics and The Challenge Of Cellular Responsesmentioning

confidence: 99%

Oxygen: A Stimulus, Not “Only” a Drug

Balestra

Kot

2021

Medicina

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Depending on the oxygen partial pressure in a tissue, the therapeutic effect of oxygenation can vary from simple substance substitution up to hyperbaric oxygenation when breathing hyperbaric oxygen at 2.5–3.0 ATA. Surprisingly, new data showed that it is not only the oxygen supply that matters as even a minimal increase in the partial pressure of oxygen is efficient in triggering cellular reactions by eliciting the production of hypoxia-inducible factors and heat-shock proteins. Moreover, it was shown that extreme environments could also interact with the genome; in fact, epigenetics appears to play a major role in extreme environments and exercise, especially when changes in oxygen partial pressure are involved. Hyperbaric oxygen therapy is, essentially, “intermittent oxygen” exposure. We must investigate hyperbaric oxygen with a new paradigm of treating oxygen as a potent stimulus of the molecular network of reactions.

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Correlation of DNA methylation patterns to the phenotypic features of Tibetan elite alpinists in extreme hypoxia

Cited by 7 publications

References 42 publications

Oxidative Stress Response’s Kinetics after 60 Minutes at Different (30% or 100%) Normobaric Hyperoxia Exposures

Oxidative Stress Response’s Kinetics after 60 Minutes at Different (30% or 100%) Normobaric Hyperoxia Exposures

Superposition extreme high-altitude exposure (8848m) forms episodic memory of LIPN and PLCH1 genes associated

Oxygen: A Stimulus, Not “Only” a Drug

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