{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T17:51:39Z","timestamp":1792950699506,"version":"4.5.0"},"reference-count":162,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Human populations native to high altitude have evolved distinct physiological adaptations to chronic hypoxia. This adaptation is evident in the O\n                    <jats:sub>2<\/jats:sub>\n                    transport cascade. In this review, with brief inclusion of the related genetic adaptations, we compare the O\n                    <jats:sub>2<\/jats:sub>\n                    cascade across three well\u2010characterized high\u2010altitude populations: Andeans (Aymara and Quechua), Tibetans\/Sherpa and Ethiopians (Amhara and Oromo). We contrast the steps of the O\n                    <jats:sub>2<\/jats:sub>\n                    cascade: (1) ventilation; (2) pulmonary O\n                    <jats:sub>2<\/jats:sub>\n                    diffusion; (3) cardiac output and circulation; (4) haematological traits; and (5) tissue O\n                    <jats:sub>2<\/jats:sub>\n                    utilization. Tibetans exhibit a robust hypoxic ventilatory response and efficient pulmonary diffusion capacity. They maintain preserved cardiac function with optimized muscle energetics. These adaptations are supported by enhanced tissue blood flow and greater muscle capillary density. Andeans demonstrate a blunted ventilatory response and marked remodelling of the pulmonary circulation, resulting in elevated pulmonary arterial pressure and mild but persistent right ventricular hypertrophy along with lifelong sympathetic overactivity. They also show strong haematological adaptations, with increased haemoglobin concentration. Ethiopians, particularly Amhara highlanders, show ventilatory status close to sea\u2010level values, with limited pulmonary and cerebral vasoreactivity to hypoxia. Although data remain limited, the Amhara highlanders exhibit higher oxygen saturation and enhanced tissue blood flow in comparison to Oromo counterparts. In conclusion, these physiological (i.e., O\n                    <jats:sub>2<\/jats:sub>\n                    cascade) differences provide evidence of the diverse patterns of evolutionarily adaptive responses to the stresses of high\u2010altitude hypoxia. Further research comparing the O\n                    <jats:sub>2<\/jats:sub>\n                    cascade across these Indigenous populations will enhance our understanding of the genetic and physiological adaptations to life at high altitude.\n                  <\/jats:p>","DOI":"10.1113\/ep092811","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T02:41:07Z","timestamp":1758768067000},"page":"849-865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Human adaptation to high\u2010altitude: A contemporary comparison of the oxygen cascade in Andean, Tibetan and Ethiopian highlanders"],"prefix":"10.1113","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1192-3359","authenticated-orcid":false,"given":"Ayechew A.","family":"Getu","sequence":"first","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health University of British Columbia  Okanagan British Columbia Canada"},{"name":"Department of Physiology, College of Medicine and Health Sciences University of Gondar  Gondar Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Ilardo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, University of Utah School of Medicine University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1667-294X","authenticated-orcid":false,"given":"Joshua C.","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Cardiff School of Sport and Health Sciences Cardiff Metropolitan University  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay M. J. R.","family":"Carr","sequence":"additional","affiliation":[{"name":"Institute of Mountain Emergency Medicine Eurac Research  Bolzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitalie","family":"Faoro","sequence":"additional","affiliation":[{"name":"Research Unit in Cardio\u2010respiratory Physiology, Exercise &amp; Nutrition, Faculty of Human Motor Sciences Universit\u00e9 libre de Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip N.","family":"Ainslie","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health University of British Columbia  Okanagan British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01167.2010"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003110"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2009.08.002"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47735-1"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-5639-7_19"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00439.2022"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.16.7583"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2012.12.011"},{"issue":"1","key":"e_1_2_11_10_1","first-page":"201","article-title":"Tibetan and Andean Patterns of Adaptation to High\u2010Altitude Hypoxia","volume":"72","author":"Beall C. 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