Everest Expedition Reveals Muscle Changes at Altitude
More research from the 2007 Caudwell Xtreme Everest expedition has been published this month in the prestigious FASEB Journal. The paper is the product of collaboration between the UCL Centre for Altitude, Space and Extreme Environment Medicine (CASE) team and Dr Andrew Murray's group at the University of Cambridge. The study investigated how individuals? muscles changed as they ascended to high altitude, particularly looking at the changes that occur to the mitochondria, the molecular powerhouses of the cell.
The mitochondria are the final destination for almost all of the oxygen entering the body, and it is here that oxygen is used to burn fuel molecules such as fats and carbohydrates, releasing energy for cells to use. In a muscle cell, the mitochondria play a vital role in providing the energy required for contraction, in the form of adenosine triphosphate (ATP). Endurance exercise training increases the density of mitochondria in muscle, allowing runners to go further before they fatigue. Professor Hans Hoppeler of the University of Bern in Switzerland, a collaborator of the Xtreme Everest Research Group and co-author on this latest paper, had previously shown that climbers returning from the summit of Everest had lost about 20% of the mitochondria from their muscle cells, but the work in this latest paper has taken the finding much further.
During the 2007 expedition, Dr Denny Levett from UCL CASE and Deputy Research Lead of the CXE expedition, took small samples of thigh muscle from 17 members of the Xtreme Team ? the first such samples ever to be collected at Everest Base Camp. These samples were rapidly frozen and sent to the Universities of Cambridge and Bern for analysis, along with similar samples taken from the same team members in London before the expedition.
Using a high-resolution electron microscope, the team made very detailed pictures of the muscles and found that the climbers lost 20% of their mitochondria, just as in the previous study, but that this wasn?t a uniform loss across the whole of the muscle cell. Dr Andrew Murray, the study?s senior author explains: ?We know that there are two populations of mitochondria in the muscle cell. Both use oxygen to make ATP, but it?s thought that each population provides ATP for different functions. We found that the subjects lost about 70% of the mitochondria that lie alongside the cell membrane, but only about 15% of those that are more central in the muscle cell. This striking finding might suggest that when oxygen supply is limited the muscle chooses to sacrifice some of its energy-requiring functions in favour of maintaining others.?
The study also found that mitochondria are not lost immediately upon ascending to high altitude, and have identified that a protein, called uncoupling protein 3, which affects how efficiently mitochondria can use oxygen, may protect muscle mitochondria in the early phase of acclimatisation. Dr Murray comments: ?Certainly, the changes after 19 days at altitude were very different to those occurring in the climbers who spent over 60 days at altitude. The early response may relate to short-term protection, whereas the later responses are probably more appropriate for a sustained period of time at high altitude. These time-dependent changes may reflect the way that many of us felt exhausted when first arriving at Base Camp, whereas after a longer stay, people have fully acclimatised and feel more energetic.?
Dr Denny Levett, one of the lead authors of the paper, explained how the findings have much wider implications: ?Patients in intensive care wards, like climbers at altitude, have chronically low blood oxygen levels. By understanding how the muscles of healthy individuals respond to low oxygen at altitude, we hope to shed new light on the way in which tissue function might be preserved in critically ill patients despite them being hypoxic, potentially aiding their recovery. Fundamental studies, such as this one, could pave the way for novel therapies in years to come.?
In the conclusions of the paper, the authors note that the muscle responses to altitude vary to some extent from individual to individual and more work is needed to identify whether the changes that occur in those who adapt most successfully to high altitude correspond with similar changes in those who make a successful recovery from critical illness. The team plan to carry out related studies in a much larger cohort of individuals to answer this question, and are currently seeking grant funding to support this vital work.
Story by Ali Cobb