title: King of the mountains: Tibetan and Sherpa physiological adaptations for life at high altitude.
abstract: Anecdotal evidence surrounding Tibetans' and Sherpas' exceptional tolerance to hypobaric hypoxia has been recorded since the beginning of high-altitude exploration. These populations have successfully lived and reproduced at high altitude for hundreds of generations with hypoxia as a constant evolutionary pressure. Consequently, they are likely to have undergone natural selection toward a genotype (and phenotype) tending to offer beneficial adaptation to sustained hypoxia. With the advent of translational human hypoxic research, in which genotype/phenotype studies of healthy individuals at high altitude may be of benefit to hypoxemic critically ill patients in a hospital setting, high-altitude natives may provide a valuable and intriguing model. The aim of this review is to provide a comprehensive summary of the scientific literature encompassing Tibetan and Sherpa physiological adaptations to a high-altitude residence. The review demonstrates the extent to which evolutionary pressure has refined the physiology of this high-altitude population. Furthermore, although many physiological differences between highlanders and lowlanders have been found, it also suggests many more potential avenues of investigation.
authors.affiliation: University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, United Kingdom; University College London Division of Surgery and Interventional Science, Royal Free Hospital, London, United Kingdom; University College Hospital London NIHR Biomedical Research Centre, London, United Kingdom; e.gilbert@ucl.ac.uk.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Gilbert-Kawai
authors.affiliation: University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, United Kingdom;
authors.forename: James S
authors.initials: JS
authors.lastname: Milledge
authors.affiliation: University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, United Kingdom; University College Hospital London NIHR Biomedical Research Centre, London, United Kingdom; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, University of Southampton, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; and Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom.
authors.forename: Michael P W
authors.initials: MP
authors.lastname: Grocott
authors.affiliation: University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, United Kingdom; University College London Division of Surgery and Interventional Science, Royal Free Hospital, London, United Kingdom; University College Hospital London NIHR Biomedical Research Centre, London, United Kingdom;
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Martin
mesh_terms: D000064:Acclimatization; D000531:Altitude; D002319:Cardiovascular System / Q000503:physiopathology*; D004734:Energy Metabolism; D059647:Gene-Environment Interaction; D005838:Genotype; D006439:Hemodynamics; D006801:Humans; D000860:Hypoxia / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology*; D008168:Lung / Q000503:physiopathology*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000503:physiopathology*; D010641:Phenotype; D012119:Respiration; D012641:Selection, Genetic; D018609:Tibet / Q000453:epidemiology