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Swiss National Science Foundation project demonstrates inherited ability to adapt to life at high altitudes

February 19, 2004

Extra enzymes protect Tibetans against muscle damage at high altitudes

Tibetans' muscles are better protected against hypoxia at high altitudes than those of lowland dwellers since Tibetans produce more of the enzymes that neutralize free radicals in muscle tissue. This ability to adapt to life at over 3,500 metres above sea level is at least partly inherited. This was the finding of a Swiss National Science Foundation project undertaken by the sports physician Hans Hoppeler from the University of Berne.

High-altitude expeditions are physically demanding because the oxygen content of the air decreases as altitude increases. At 5,000 metres there is just one third the amount of oxygen that there is at sea level. This oxygen deficiency, or hypoxia, has adverse effects not only on the lungs and brains (altitude sickness), but also on the muscles of mountain climbers originating from low altitudes.

This was the finding of the sports physician Hans Hoppeler and his team at the Department of Systematic Anatomy at the University of Berne back in the 1980s when they investigated members of two Swiss Everest expeditions: the number of mitochondria, the power plants of the cells, declined and evidence of cell damage was found in muscle tissue samples. Amazingly, the indigenous porters, the sherpas, were immune to such muscle damage.

It is known that hypoxia leads to the formation of free radicals (highly reactive atoms or molecules with an unpaired electron), which attack the mitochondria. Are the Tibetans less affected by this phenomenon? Do their bodies adapt to the hypoxia over the course of their life or have these people, whose ancestors colonised the Tibetan plateau some 15,000 years ago, also genetically adapted to the exceptional conditions?

A joint Swiss/Italian team headed by Hans Hoppeler conducted a comparative study to answer these questions. They investigated nine Tibetans residing at altitudes between 3500 and 4500 metres and six Tibetans whose parents had emigrated to the lowlands (approx. 1,500 metres above sea level). The control group consisted of nine Nepalese from the lowlands (approx. 1,500 metres above sea level). After obtaining the approval of all the relevant ethics committees, the researchers collected tiny samples of muscle tissue in order to investigate various proteins, among which enzymes (those biological catalyst that speed up chemical reactions)

Protection against free radicals
The results, which have just been published electronically in the professional "FASEB Journal", are clear: Tibetans have significantly higher levels of the enzyme glutathione-S-transferase, which neutralizes free radicals in the tissues (a then so called antioxidant) - around 380 percent in the Himalayan Tibetans and by 50 percent in the lowland-dwelling Tibetans compared to the Nepalese. "Thanks to this enzyme the Tibetans are presumably better equipped to neutralize the free radicals produced as a result of the hypoxia", explains Hoppeler. If this conclusion is correct, the Himalayan Tibetans should also possess fewer degraded mitochondria than Western mountain climbers. This was subsequently confirmed in follow-up studies on muscle samples collected during previous investigations. "Since those Tibetans who had never been exposed to hypoxia also showed higher levels of this antioxidant, this adaptation is probably at least partly inherited. We are currently investigating the adaptation at genetic level", says Hans Hoppeler

Another distinct difference between Tibetans and Nepalese identified by the researchers related to the enzyme enoyl coenzyme A hydratase, which oxidizes fatty acids in the mitochondria to produce energy. Here again the muscle tissue of both groups of Tibetans - mountain-dwellers and lowlanders - contained more of this enzyme. "The lipid metabolism of the Tibetans is presumably faster than that of the low-altitude dwellers", concludes Hoppeler. "This optimal utilization of fat reserves could provide benefits during physical exertion in the mountains and aid thermoregulation in cold temperatures." This adaptation also appears to be inherited since it was observed not only in the Himalayan Tibetans but also in those living at low altitude.

Hans Hoppeler believes that this study confirms his earlier observations among members of Swiss Everest expeditions. Sports physicians have been aware for some time now that hypoxia as a factor in high-altitude training should only be used selectively, for example during sleep or during certain types of muscle training. Nowadays, hypoxia is restricted to the minimum required to achieve a defined level of adaptation in training. Nevertheless, the mechanisms involved in adapting to chronic hypoxia are of general medical interest, for example in helping us understand the consequences of chronic obstructive pulmonary disease (COPD).

* "New aspects of altitude adaptation in Tibetans: a proteomic approach", FASEB Journal, 20 January 2004 (electronic pre-publication)

Schweizerischer Nationalfonds zur Foerderung der wissenschaftlichen Forschung