̽��ֱ�� of Cambridge - Andrew Murray

Himalayan powerhouses: how Sherpas have evolved superhuman energy efficiency

cjb250 — Mon, 22 May 2017 19:00:54 +0000

̽��ֱ��findings could help scientists develop new ways of treating hypoxia – lack of oxygen – in patients. A significant proportion of patients in intensive care units (ICUs) experience potentially life-threatening hypoxia, a complication associated with conditions from haemorrhage to sepsis.

When oxygen is scarce, the body is forced to work harder to ensure that the brain and muscles receive enough of this essential nutrient. One of the most commonly observed ways the body has of compensating for a lack of oxygen is to produce more red blood cells, which are responsible for carrying oxygen around the body to our organs. This makes the blood thicker, however, so it flows more slowly and is more likely to clog up blood vessels.

Mountain climbers are often exposed to low levels of oxygen, particularly at high altitudes. This is why they often have to take time during long ascents to acclimatise to their surroundings, giving the body enough time to adapt itself and prevent altitude sickness. In addition, they may take oxygen supplies to supplement the thin air.

Scientists have known for some time that people have different responses to high altitudes. While most climbers require additional oxygen to scale Mount Everest, whose peak is 8,848m above sea level, a handful of climbers have managed to do so without. Most notably, Sherpas, an ethnic group from the mountain regions of Nepal, are able to live at high altitude with no apparent consequences to their health – as a result, many act as guides to support expeditions in the Himalayas, and two Sherpas are known to have reached the summit of Everest an incredible 21 times.

Previous studies have suggested differences between Sherpas and people living in non-high altitude areas, known collectively as ‘lowlanders’, including fewer red blood cells in Sherpas at altitude, but higher levels of nitric oxide, a chemical that opens up blood vessels and keeps blood flowing.

Evidence suggests that the first humans were present on the Tibetan Plateau around 30,000 years ago, with the first permanent settlers appearing between 6,000-9,000 years ago. This raises the possibility that they have evolved to adapt to the extreme environment. This is supported by recent DNA studies, which have found clear genetic differences between Sherpa and Tibetan populations on the one hand and lowlanders on the other. Some of these differences were in their mitochondrial DNA – the genetic code that programmes mitochondria, the body’s ‘batteries’ that generate our energy.

To understand the metabolic differences between the Sherpas and lowlanders, a team of researchers led by scientists at the ̽��ֱ�� of Cambridge followed two groups as they made a gradual ascent up to Everest Base Camp at an elevation of 5,300m. ̽��ֱ��expedition, Xtreme Everest 2, was led by Dr Daniel Martin from ̽��ֱ�� College London.

Xtreme Everest is a project that aims to improve outcomes for people who become critically ill by understanding how our bodies respond to the extreme altitude on the world’s highest mountain. This year marks 10 years since the group’s first expedition to Everest.

̽��ֱ��lowlanders group comprised 10 investigators selected to operate the Everest Base Camp laboratory, where the mitochondrial studies were carried out by James Horscroft and Aleks Kotwica, two PhD students at the ̽��ֱ�� of Cambridge. They took samples, including blood and muscle biopsies, in London to give a baseline measurement, then again when they first arrived at Base Camp and a third time after two months at Base Camp. These samples were compared with those taken from 15 Sherpas, all of whom were living in relatively low-lying areas, rather than being the ‘elite’ high altitude climbers. ̽��ֱ��Sherpas’ baseline measurements were taken at Kathmandu, Nepal.

̽��ֱ��researchers found that even at baseline, the Sherpas’ mitochondria were more efficient at using oxygen to produce ATP, the energy that powers our bodies.

As predicted from genetic differences, they also found lower levels of fat oxidation in the Sherpas. Muscles have two ways to get energy – from sugars, such as glucose, or from burning fat (fat oxidation). ̽��ֱ��majority of the time we get our energy from the latter source; however, this is inefficient, so at times of physical stress, such as when exercising, we take our energy from sugars. ̽��ֱ��low levels of fat oxidation again suggest that the Sherpas are more efficient at generating energy.

̽��ֱ��measurements taken at altitude rarely changed from the baseline measurement in the Sherpas, suggesting that they were born with such differences. However, for lowlanders, measurements tended to change after time spent at altitude, suggesting that their bodies were acclimatising and beginning to mimic the Sherpas’ bodies.

One of the key differences, however, was in phosphocreatine levels. Phosphocreatine is an energy reserve that acts as a buffer to help muscles contract when no ATP is present. In lowlanders, after two months at high altitude, phosphocreatine levels crash, whereas in Sherpas levels actually increase.

In addition, the team found that while levels of free radicals increase rapidly at high altitude, at least initially, levels in Sherpas are very low. Free radicals are molecules created by a lack of oxygen that can be potentially damaging to cells and tissue.

“Sherpas have spent thousands of years living at high altitudes, so it should be unsurprising that they have adapted to become more efficient at using oxygen and generating energy,” says Dr Andrew Murray from the ̽��ֱ�� of Cambridge, the study’s senior author. “When those of us from lower-lying countries spend time at high altitude, our bodies adapt to some extent to become more ‘Sherpa-like’, but we are no match for their efficiency.”

̽��ֱ��team say the findings could provide valuable insights to explain why some people suffering from hypoxia fare much worse in emergency situations that others.

“Although lack of oxygen might be viewed as an occupational hazard for mountain climbers, for people in intensive care units it can be life threatening,” explains Professor Mike Grocott, Chair of Xtreme Everest from the ̽��ֱ�� of Southampton. “One in five people admitted to intensive care in the UK each year die and even those that survive might never regain their previous quality of life.

“By understanding how Sherpas are able to survive with low levels of oxygen, we can get clues to help us identify those at greatest risk in ICUs and inform the development of better treatments to help in their recovery.”

Dr Martin adds: “These findings are an important step forward for our translational research programme. They provide us with an insight as to how Shepras have adapted to low oxygen levels over countless generations. This new piece of the jigsaw will hopefully lead us towards finding new treatments that will benefit patients in intensive care.”

̽��ֱ��research was part-funded by the British Heart Foundation.

Reference
Horscroft, J et al. Metabolic basis to Sherpa altitude adaptation. PNAS; 22 May 2017; DOI: 10.1073/pnas.1700527114

Sherpas have evolved to become superhuman mountain climbers, extremely efficient at producing the energy to power their bodies even when oxygen is scarce, suggests new research published in the Proceedings of National Academy of Sciences (PNAS).

Sherpas have spent thousands of years living at high altitudes, so it should be unsurprising that they have adapted to become more efficient at using oxygen and generating energy

Andrew Murray

How Sherpas have evolved ‘superhuman’ energy efficiency

Niklassletteland

Sherpas on the Trail Nearing Lobuche, Nepal

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High-fat diet affects physical and memory abilities

bjb42 — Thu, 13 Aug 2009 00:00:00 +0000

̽��ֱ��research, funded by the British Heart Foundation and published in the FASEB Journal, may have implications not only for those eating lots of high-fat foods, but also athletes looking for the optimal diet for training and patients with metabolic disorders.

"We found that rats, when switched to a high-fat diet from their standard low-fat feed, showed a surprisingly quick reduction in their physical performance," says Dr Andrew Murray, who led the work while at Oxford ̽��ֱ�� and is currently at the ̽��ֱ�� of Cambridge. "After just nine days, they were only able to run 50 per cent as far on a treadmill as those that remained on the low-fat feed."

High-fat diets, such as those that are prevalent in Western countries, are known to be harmful in the long term and can lead to problems such as obesity, diabetes and heart failure. They are also known to be associated with a decline in cognitive ability over long time spans. But little attention has been paid to the effect of high-fat diets in the short term.

Physical endurance - how long we can keep exercising - depends on how much oxygen can be supplied to our muscles and how efficiently our muscles release energy by burning up the fuel we get from the food we eat. In particular, using fat as a fuel is less efficient than using glucose from carbohydrates, but the metabolic changes induced by different diets are complex and it has been controversial whether high-fat feeding for a short time would increase or decrease physical performance.

̽��ֱ��team set out to investigate whether rats fed a high-fat diet for just a few days showed any change in their physical and cognitive abilities.

All 42 rats were initially fed a standard feed with a low fat content of 7.5 per cent. Their physical endurance was measured by how long they could run on a treadmill and their short-term or 'working' memory was measured in a maze task. Half of the rats were then switched to a high-fat diet where 55 per cent of the calories came from fat. After four days of getting used to the new diet, the endurance and cognitive performance of the rats on the low- and high-fat diets was compared for another five days.

"With the standard feed, 7.5 per cent of the calories come from fat. That's a pretty low-fat diet, much like humans eating nothing but muesli," says Dr Murray. " ̽��ֱ��high-fat diet, in which 55 per cent of the calories came from fat, sounds high but it's actually not extraordinarily high by human standards. A junk food diet would come close to that.

"Some high-fat, low-carb diets for weight loss can even have fat contents as high as 60 per cent. However, it's not clear how many direct conclusions can be drawn from our work for these diets, as the high-fat diet we used was not particularly low in carbs," he adds.

On the fifth day of the high-fat diet (the first day back on the treadmill), the rats were already running 30 per cent less far than those remaining on the low-fat diet. By the ninth day, the last of the experiment, they were running 50 per cent less far.

̽��ֱ��rats on the high-fat diet were also making mistakes sooner in the maze task, suggesting that their cognitive abilities were also being affected by their diet. ̽��ֱ��number of correct decisions before making a mistake dropped from over six to an average of 5 to 5.5.

̽��ֱ��researchers also investigated what metabolic changes the high-fat diet was inducing in the rats. They found increased levels of a specific protein called the 'uncoupling protein' in the muscle and heart cells of rats on the high-fat diet. This protein 'uncouples' the process of burning food stuffs for energy in the cells, reducing the efficiency of the heart and muscles. This could at least partly explain the reduction in treadmill running seen in the rats.

̽��ֱ��rats that were fed a high fat diet and had to run on the treadmill also had a significantly bigger heart after nine days, suggesting the heart had to increase in size to pump more blood around the body and get more oxygen to the muscles.

While this research has been done in rats, the Oxford team and Andrew Murray's new group in Cambridge are now carrying out similar studies in humans, looking at the effect of a short term high-fat diet on exercise and cognitive ability.

̽��ֱ��results will be important not only in informing athletes of the best diets to help their training routine, but also in developing ideal diets for patients with metabolic disorders such as diabetes, insulin resistance or obesity. People with such conditions can have high levels of fat in the blood and show poor exercise tolerance, some cognitive decline, and can even develop dementia over time.

"In little more than a week, a change in diet appears to have made the rats' hearts much less efficient," says Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, who funded the research. "We look forward to the results of the equivalent studies in human volunteers, which should tell us more about the short-term effects of high-fat foods on our hearts. We already know that to protect our heart health in the long-term, we should cut down on foods high in saturated fat."

Rats fed a high-fat diet show a stark reduction in their physical endurance and a decline in their cognitive ability after just nine days, a new study has shown.

With the standard feed, 7.5 per cent of the calories come from fat. That's a pretty low-fat diet, much like humans eating nothing but muesli. ̽��ֱ��high-fat diet, in which 55 per cent of the calories came from fat, sounds high but it's actually not extraordinarily high by human standards. A junk food diet would come close to that.

Dr Andrew Murray

Credit:the_bosshog via Flickr

Poppy the rat says hello

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