Sherpas are a minority ethnic population who live at
elevations that are mind-blowing, even to us mile-high folk! Living at
elevations of up to 4,000m, this population thrives at an altitude at which 50%
(at 4,000m) of people develop acute mountain sickness (Taylor, 2011). Yet, in
the Sherpa population, acute mountain sickness simply does not occur at 4,000m.
The battery of vile symptoms: headache, nausea, vomiting, weakness, dizziness,
and difficulty sleeping do not weaken Sherpas and therefore they are relied
upon to lead expeditions in Nepal, including ascents of Mount Everest (8,800m).
Of course, Sherpas have to acclimate to
altitudes as extreme as Everest, however, their baseline ability to avoid acute
mountain sickness (AMS) at 4,000m is astonishing.
It turns out that one genetic component to this feat is the prevalence
of an insertion polymorphism in the angiotensin-converting enzyme (ACE) gene. This
ACE insertion (I) allele was first noticed in Caucasian mountain climbers who
ascended to extremely high altitudes without supplemental oxygen, so it was
chosen as a candidate gene for testing in the Sherpa population. Japanese
researchers found that Sherpas were significantly more likely to carry the ACE
I allele when compared to their peers who lived at lower altitude in Katmandu
(1,400m) (Droma et. al, 2005).
Why does the ACE I allele matter?
When humans are exposed to high altitude, ACE levels tend to increase. ACE converts AngI to AngII and increases aldosterone levels. This induces vasoconstriction and sodium retention, which is associated with edema. If Sherpas are able to keep their circulating ACE levels low at altitude then they decrease their risk of vasoconstriction and edema, allowing their bodies to function as they would at lower altitudes. The ACE I allele may therefore play a fundamental role in maintaining low levels of circulating ACE levels, thereby decreasing Sherpas’ risk of developing AMS (Droma et. al, 2005).
Taylor, A. T. (2011, January). High-Altitude Illnesses: Physiology, Risk Factors, Prevention, and Treatment. Retrieved October 13, 2017, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678789/
This is such a neat discovery! This is very relevant to everyday life as there are multiple deaths each year from acute mountain sickness (there were 10 deaths alone in Colorado on 14ers in 2010) and researchers have now found why certain people are better acclimated to higher altitudes than others. While reading your post I started to wonder if it possible for all humans to eventually develop/evolve this gene, or can competitive climbers somehow undergo a gene therapy procedure to input or develop that gene in their system? If more people were to have the ACE I allele there could be a potential decrease in deaths from acute mountain sickness.
ReplyDeletehttp://www.alanarnette.com/co14ers/fourteenersfaq.php
Hey Alex! This is a fantastic article, and I can appreciate why you chose an article like this given your passion for hiking. I think it would be interesting to compare the expressivity of the ACE I allele in populations at sea level, populations who live above sea level in places like Denver, and then populations like the Sherpas who live in environments at an even higher altitude. I wonder if this change in the ACE I allele starts occurring in any population at altitude, or only in populations at very high altitudes like the Sherpa populations. In conjunction with aldosterone, I wonder if there is also a change in antidiuretic hormone (ADH) levels among populations of Sherpas. ADH stimulates retention of water in the distal convoluted tubule and collecting duct in the kidney. Since ADH and aldosterone have similar functions and respond to similar changes in homeostasis, I would also expect there to be a change in a gene or allele involving ADH in the Sherpa populations.
ReplyDeleteVery interesting! I've also wondered about how these sherpas make summiting Everest look so blase. I wrote an article on this blog on physiological changes free divers undergo to withstand deep water hypoxia (as well as pressure). A lot of cursory reading I did from the article seemed to hint at the idea that some could be free divers and others could not, regardless of practice. I wonder if ACE I has anything to do with this penchant for breath holding far beyond normal human limits (around 4 minutes in free-dive open water scenarios).
ReplyDeleteThis is interesting as I always thought Sherpas were better climbers because they practiced a lot but role of genetic difference never struck my mind. Could this increase in ACE I level when exposed to higher altitudes contribute to headaches? I often get that when attempting 14ers. It does make sense that with more ACE levels, blood pressure increases due to vasoconstriction and sodium retention. Drugs like Diamox used for altitude sickness works by getting rid of the water, like a diuretic. I wonder if people who climbed Mt. Everest took medications to help them acclimatize efficiently.
ReplyDeleteHow does this genetic difference affect their hemoglobin level and ability to survive during hypoxic conditions? Here's what I found. Even at elevations of 14,000 feet above sea level or higher, where the atmosphere contains much less oxygen than at sea level, most Tibetans (who also live in high altitudes) not overproduce red blood cells and do not develop lung or brain complications. The researchers found evidence that this might be related to at least 10 genes, two of which are specific genes strongly associated with hemoglobin, a molecule that transports oxygen in the blood. Researchers discovered in 2010 that Tibetans have several genes that help them use smaller amounts of oxygen efficiently, allowing them to deliver enough of it to their limbs while exercising at high altitude. Most notable is a version of a gene called EPAS1, which regulates the body’s production of hemoglobin.
This is interesting as to how human body evolves to adjust to any situations.
http://www.sciencemag.org/news/2014/07/tibetans-inherited-high-altitude-gene-ancient-human. (n.d.).
Cool article for a people that are very interesting. I have always wondered how Sherpas are so great at doing what they do and this was a good physiological breakdown of that. Other than the ACE gene, do you know if Sherpas posses any other difference in their physiology that allows them to be such great mountaineers? Are they able to take in oxygen more efficiently because of their long history of living at extraordinary elevations? Do they produce more energy at high altitudes than a person who is from a lower elevation that is summiting the same mountain? A article that I found on the Smithsonian website offered some other reasons as to how Sherpas are such great mountaineers, which are more reasons as to why they are less prone to acute mountain sickness.
ReplyDeletehttps://www.smithsonianmag.com/smart-news/sherpas-evolved-live-and-work-altitude-180963438/
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