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Human adaptation to high altitude: regional and life-cycle perspectives.

Studies of the ways in which persons respond to the adaptive challenges of life at high altitude have occupied an important place in anthropology. There are three major regions of the world where high-altitude studies have recently been performed: the Himalayas of Asia, the Andes of South America, and the Rocky Mountains of North America. Of these, the Himalayan region is larger, more geographically remote, and likely to have been occupied by humans for a longer period of time and to have been subject to less admixture or constriction of its gene pool. Recent studies of the physiological responses to hypoxia across the life cycle in these groups reveal several differences in adaptive success. Compared with acclimatized newcomers, lifelong residents of the Andes and/or Himalayas have less intrauterine growth retardation, better neonatal oxygenation, and more complete neonatal cardiopulmonary transition, enlarged lung volumes, decreased alveolar-arterial oxygen diffusion gradients, and higher maximal exercise capacity. In addition, Tibetans demonstrate a more sustained increase in cerebral blood flow during exercise, lower hemoglobin concentration, and less susceptibility to chronic mountain sickness (CMS) than acclimatized newcomers. Compared to Andean or Rocky Mountain high-altitude residents, Tibetans demonstrate less intrauterine growth retardation, greater reliance on redistribution of blood flow than elevated arterial oxygen content to increase uteroplacental oxygen delivery during pregnancy, higher levels of resting ventilation and hypoxic ventilatory responsiveness, less hypoxic pulmonary vasoconstriction, lower hemoglobin concentration, and less susceptibility to CMS. Several of the distinctions demonstrated by Tibetans parallel the differences between natives and newcomers, suggesting that the degree of protection or adaptive benefit relative to newcomers is enhanced for the Tibetans. We thus conclude that Tibetans have several physiological distinctions that confer adaptive benefit consistent with their probable greater generational length of high-altitude residence. Future progress is anticipated in achieving a more integrated view of high-altitude adaptation, incorporating a sophisticated understanding of the ways in which levels of biological organization are articulated and a recognition of the specific genetic variants contributing to differences among high-altitude groups.