Scientifically Speaking | Unlocking the mysteries of high-altitude survival
The Sherpas’ resistance to altitude sickness is rooted in evolution, from a mutation in the EPAS1 gene to their body's ability to process glucose for energy
A few years ago, while hiking in the Andes in Peru, I found myself battling altitude sickness. The symptoms were all too familiar, including a pounding headache, nausea, and the unsettling sensation of not getting enough air. Rest and hydration helped, but only so much. The only recourse was to get down to lower elevations. Meanwhile, the locals went about their day without any visible discomfort.
Altitude sickness has hit me in other high places as well, from the Himalayas to the Rocky Mountains in Colorado. Yet, sherpas, renowned as high-altitude dwellers of the Himalayas seem mostly unaffected in similar conditions. They perform incredible feats of endurance at elevations that leave most of us gasping for air. So, what makes sherpas more resistant to the effects of high altitude than most of us plains dwellers?
Sherpas have lived in Nepal for over 500 years, migrating from Tibet to eastern Nepal. Over time, they have developed remarkable adaptations that allow them to thrive where others struggle. Their legendary performance at extreme altitudes, like the upper slopes of Mount Everest, is rooted in how their bodies handle oxygen scarcity.
In low-oxygen environments, most people’s bodies try to compensate by producing more haemoglobin, the molecule that carries oxygen in the blood. However, too much haemoglobin thickens the blood, making it harder for the heart to pump, leading to complications and altitude sickness. Sherpas avoid this by using oxygen more efficiently, thanks to a mix of genetic mutations and unique metabolic adaptations.
A key genetic factor is the EPAS1 gene, a variant that regulates the body’s response to low oxygen, or hypoxia. Discovered in 2010, and reported in the journal Nature, this gene variant is a remnant of an ancient human relative, the Denisovans. These now-extinct humans, known from a single bone found in Siberia, interbred with early modern humans tens of thousands of years ago. Their legacy, including the EPAS1 gene, is found in sherpas and Tibetans, where it has helped them live at high altitudes by preventing the dangerous overproduction of haemoglobin. This allows their bodies to function better at high altitudes.
There are other advantages as well. In 2017, a study from the University of Cambridge published in Proceedings of the National Academy of Sciences explored the unique metabolism of sherpas, showing that they have an edge in how their bodies process oxygen. Sherpas burn glucose instead of fat for energy, which provides more energy per oxygen molecule. This is a crucial advantage when oxygen is scarce. Their muscles and the mitochondria (the tiny powerhouses in cells) are finely tuned to extract the most energy from every breath. This lets them sustain physical activity with far less oxygen than lowlanders such as myself.
While lowlanders can adapt to high altitudes by increasing red blood cells and haemoglobin, this response is temporary and comes with risks like thicker blood and a higher chance of stroke. Sherpas, however, show little to no increase in haemoglobin. Instead, their genetic and metabolic adaptations ensure a steady flow of oxygen to vital organs without overloading their cardiovascular systems. Their ability to avoid blood thickening is a testament to thousands of years of adaptation. Human settlements on the Tibetan Plateau date as far back as 30,000 years, with permanent settlements appearing 6,000 to 9,000 years ago. That long history gave natural selection time to favour genes and traits that enhance survival in these hypoxic environments.
Other high-altitude populations, such as the Andean people of South America, have developed their own adaptations, though they differ from the sherpas. For instance, Andean populations tend to have larger lungs and chest cavities, which help them take in more oxygen with each breath. Their haemoglobin levels are also higher than those of lowlanders, but not excessively so, allowing them to avoid some of the risks of thickened blood. These populations have lived at high altitudes for thousands of years but for less time than the Tibetans and Sherpas.
But recent research has also revealed that there’s some hope that plains dwellers can adapt over time to higher elevations. The gut microbiome, which is the collection of the diverse microbes living in our digestive systems, plays a critical role in high-altitude adaptation. In August, a study published in Genome Biology by Qing-Peng Kong and his team at the Chinese Academy of Sciences highlighted the role of a gut bacterium called Blautia. In their study, Kong’s team observed a group of Han Chinese men temporarily moved from lowland areas to the high-altitude Tibetan Plateau. Over three months, their gut microbiomes changed, and Blautia became much more abundant.
The researchers found that Blautia might help to cope with low oxygen. It produces short-chain fatty acids that reduce inflammation and protect the gut lining. This is important because low oxygen can trigger inflammation and damage tissues, especially in the lungs and intestines. Adding Blautia in mouse studies reduced this damage, suggesting that it might help prevent altitude sickness by calming the body’s inflammatory response to low oxygen. If future research confirms this, it could lead to probiotic treatments that help lowlanders adjust more easily to high altitudes.
While most of us may struggle with the thin air of the world’s highest peaks, high-altitude dwellers are proof of humanity’s ability to adapt to even the most extreme environments. As we learn more about the role of gut bacteria like Blautia, these discoveries could one day help the rest of us better cope with low-oxygen environments ourselves.
Anirban Mahapatra is a scientist and author, most recently of the popular science book, When The Drugs Don’t Work: The Hidden Pandemic That Could End Medicine. The views expressed are personal.
A few years ago, while hiking in the Andes in Peru, I found myself battling altitude sickness. The symptoms were all too familiar, including a pounding headache, nausea, and the unsettling sensation of not getting enough air. Rest and hydration helped, but only so much. The only recourse was to get down to lower elevations. Meanwhile, the locals went about their day without any visible discomfort.
Altitude sickness has hit me in other high places as well, from the Himalayas to the Rocky Mountains in Colorado. Yet, sherpas, renowned as high-altitude dwellers of the Himalayas seem mostly unaffected in similar conditions. They perform incredible feats of endurance at elevations that leave most of us gasping for air. So, what makes sherpas more resistant to the effects of high altitude than most of us plains dwellers?
Sherpas have lived in Nepal for over 500 years, migrating from Tibet to eastern Nepal. Over time, they have developed remarkable adaptations that allow them to thrive where others struggle. Their legendary performance at extreme altitudes, like the upper slopes of Mount Everest, is rooted in how their bodies handle oxygen scarcity.
In low-oxygen environments, most people’s bodies try to compensate by producing more haemoglobin, the molecule that carries oxygen in the blood. However, too much haemoglobin thickens the blood, making it harder for the heart to pump, leading to complications and altitude sickness. Sherpas avoid this by using oxygen more efficiently, thanks to a mix of genetic mutations and unique metabolic adaptations.
A key genetic factor is the EPAS1 gene, a variant that regulates the body’s response to low oxygen, or hypoxia. Discovered in 2010, and reported in the journal Nature, this gene variant is a remnant of an ancient human relative, the Denisovans. These now-extinct humans, known from a single bone found in Siberia, interbred with early modern humans tens of thousands of years ago. Their legacy, including the EPAS1 gene, is found in sherpas and Tibetans, where it has helped them live at high altitudes by preventing the dangerous overproduction of haemoglobin. This allows their bodies to function better at high altitudes.
There are other advantages as well. In 2017, a study from the University of Cambridge published in Proceedings of the National Academy of Sciences explored the unique metabolism of sherpas, showing that they have an edge in how their bodies process oxygen. Sherpas burn glucose instead of fat for energy, which provides more energy per oxygen molecule. This is a crucial advantage when oxygen is scarce. Their muscles and the mitochondria (the tiny powerhouses in cells) are finely tuned to extract the most energy from every breath. This lets them sustain physical activity with far less oxygen than lowlanders such as myself.
While lowlanders can adapt to high altitudes by increasing red blood cells and haemoglobin, this response is temporary and comes with risks like thicker blood and a higher chance of stroke. Sherpas, however, show little to no increase in haemoglobin. Instead, their genetic and metabolic adaptations ensure a steady flow of oxygen to vital organs without overloading their cardiovascular systems. Their ability to avoid blood thickening is a testament to thousands of years of adaptation. Human settlements on the Tibetan Plateau date as far back as 30,000 years, with permanent settlements appearing 6,000 to 9,000 years ago. That long history gave natural selection time to favour genes and traits that enhance survival in these hypoxic environments.
Other high-altitude populations, such as the Andean people of South America, have developed their own adaptations, though they differ from the sherpas. For instance, Andean populations tend to have larger lungs and chest cavities, which help them take in more oxygen with each breath. Their haemoglobin levels are also higher than those of lowlanders, but not excessively so, allowing them to avoid some of the risks of thickened blood. These populations have lived at high altitudes for thousands of years but for less time than the Tibetans and Sherpas.
But recent research has also revealed that there’s some hope that plains dwellers can adapt over time to higher elevations. The gut microbiome, which is the collection of the diverse microbes living in our digestive systems, plays a critical role in high-altitude adaptation. In August, a study published in Genome Biology by Qing-Peng Kong and his team at the Chinese Academy of Sciences highlighted the role of a gut bacterium called Blautia. In their study, Kong’s team observed a group of Han Chinese men temporarily moved from lowland areas to the high-altitude Tibetan Plateau. Over three months, their gut microbiomes changed, and Blautia became much more abundant.
The researchers found that Blautia might help to cope with low oxygen. It produces short-chain fatty acids that reduce inflammation and protect the gut lining. This is important because low oxygen can trigger inflammation and damage tissues, especially in the lungs and intestines. Adding Blautia in mouse studies reduced this damage, suggesting that it might help prevent altitude sickness by calming the body’s inflammatory response to low oxygen. If future research confirms this, it could lead to probiotic treatments that help lowlanders adjust more easily to high altitudes.
While most of us may struggle with the thin air of the world’s highest peaks, high-altitude dwellers are proof of humanity’s ability to adapt to even the most extreme environments. As we learn more about the role of gut bacteria like Blautia, these discoveries could one day help the rest of us better cope with low-oxygen environments ourselves.
Anirban Mahapatra is a scientist and author, most recently of the popular science book, When The Drugs Don’t Work: The Hidden Pandemic That Could End Medicine. The views expressed are personal.