It’s not often that an epigenetics study can elevate you to a higher plane, but uplifting new research into those who live at the top of the world now establishes that DNA methylation profiles can take you higher and higher and support high-altitude living.
Researchers led by Ainash Childebayeva (Max Planck Institute for the Study of Human History, Jena, Germany) sought to explore those epigenetic mechanisms that allow certain peoples, such as the Peruvian Quechua of the Andes, to adapt to high-altitude living. While physiological and genetic adaptations to living at high altitude and in low oxygen conditions have been well documented, the potential role of epigenetic modifications in adaptive developmental plasticity has been less well explored, with only a few reports providing any encouragement.
To elevate their research to a higher level, the epigenetic explorers turned to a comparative analysis of genome-wide DNA methylation patterns in whole blood samples isolated from Peruvian Quechua with varying exposures to the high altitudes of the Andes mountains for further insight. Here’s what they found on their expedition:
- Two differentially methylated CpG sites and sixty-two differentially methylated regions associate with lifelong high-altitude exposure or developmental exposures to high altitude
- While hyper- and hypo-methylating events both occurred, high-altitude exposure favors hypermethylation
- Affected regions associate with genes regulating metabolism (LDHC), hypoxic responses (SOD3), red blood cell production (PKLR, MEIS1), blood pressure (EPHA6, GRP35), and skeletal muscle growth (PAX7)
- Interestingly, the results also suggest that genetic variation influences the DNA methylation profiles
- There exists a significant association between DNA methylation of the EPAS1 gene (also known as hypoxia-inducible factor-2 alpha), which plays a crucial role in oxygen sensing and regulation, and EPAS1-associated single nucleotide polymorphisms
- Finally, analysis of epigenetic aging (by evaluating the difference between Horvath’s epigenetic clock and chronological age) linked high altitude existence with more rapid aging
While the researchers reached dizzying heights in their exploration of the links between living at high-altitude and DNA methylation in the Peruvian Quechua, they note the need to extend their analysis to tissues other than blood and combine their DNA methylation findings with RNA, protein, and phenotypic data.
To ascend to the next epigenetic level and discover how DNA methylation can take you to higher ground, scrabble over to Genome Biology and Evolution, November 2020.