Abstract
W
In retrospect, perhaps we should not have been as surprised as we were. There was plenty of evidence suggesting an extraordinary athletic ability of Tibetans and Sherpas (who originated from Tibet) at extreme altitude. For example, two Sherpas have reached the summit of Mt. Everest 21 times. There was also suggestive phenotypical evidence. Several studies had shown that many Tibetans have an unexpectedly low hemoglobin concentration at high altitude. Interestingly, one of the first suggestions of this was measurements made by Pugh on Cho Oyu as far back as 1952 when he attributed the low hemoglobin concentrations to iron deficiency in the diet. Nevertheless, the discovery of genetic changes came as a great surprise for most people.
The articles that appeared in 2010 were remarkable in that the authors used a variety of techniques to look at the changes in the Tibetan genome. But in spite of this, there was reassuring agreement on the results. One of the most important findings was over-represented variants on chromosome 2 close to the EPAS-1 gene. EPAS stands for endothelial PAS-dominant protein 1 and it is known that this gene encodes for HIF 2-alpha. Hypoxia inducible factors are transcription factors that respond to changes in available oxygen and they play a critical role in many responses of the cell to hypoxia. These include regulation of the hemopoietin mechanism. Other changes reported in the Tibetans were over-representation of the EGLN 1 and PPARA genes which are also associated with hemoglobin concentration.
Since 2010, much research activity has been devoted to following up these initial observations. Much of the work is technical and challenging for people who have not followed this area of research. In the present issue of the Journal, Tatum Simonson presents a timely update on genetic contributions to altitude adaptation.
Another recent interest in altitude research has been the relations between aging and tolerance to altitude. All of us are growing older and increasingly, people who would not have considered going to high altitude a few years ago have now become more adventurous. The Special Topic in this issue of the Journal has four articles devoted to this area. Two are on cardiovascular issues including coronary artery disease and hypertension. One is on obstructive sleep apnea, which has approached near-epidemic status at normal altitudes, and one on the ventilatory response to hypoxia, which is one of the most important factors determining how well people cope with high altitude.
The Invited Review on genetic changes is at a rather basic scientific level, whereas the Special Topic articles on aging are very clinical in their orientation. This fits the mission of our Journal, which aims to cover the spectrum between basic biology and clinical medicine.
Earthquake in Nepal
The news of the devastating earthquake in Nepal will resonate with many readers of this Journal. Many of us have been to Kathmandu and also to the Everest Base Camp which was severely affected. One of our board members, Buddha Basnyat, lives in Kathmandu but happily his family is safe. Many of us have Sherpa friends in the Khumbu region and we worry about them and their families. Fewer people nowadays trek through the villages on the route from Kathmandu to Everest but I have had the opportunity of doing this twice, and the area has apparently sustained terrible damage. Hopefully international aid will be effective although many of the affected areas are remote and difficult to access. Opportunities for donations have been organized. However, sadly it will be a long time before the country recovers from this appalling catastrophe.