Comparative aspects of high-altitude adaptation in human populations
Abstract
The conditions and duration of high-altitude residence differ among high-altitude populations. The Tibetan Plateau is larger, more geographically remote, and appears to have been occupied for a longer period of time than the Andean Altiplano and, certainly, the Rocky Mountain region as judged by archaeological, linguistic, genetic and historical data. In addition, the Tibetan gene pool is less likely to have been constricted by small numbers of initial migrants and/or severe population decline, and to have been less subject to genetic admixture with lowland groups. Comparing Tibetans to other high-altitude residents demonstrates that Tibetans have less intrauterine growth retardation better neonatal oxygenation higher ventilation and hypoxic ventilatory response lower pulmonary arterial pressure and resistance lower hemoglobin concentrations and less susceptibility to CMS These findings are consistent with the conclusion that "adaptation" to high altitude increases with time, considering time in generations of high-altitude exposure. Future research is needed to compare the extent of IUGR and neonatal oxygenation in South American high-altitude residents of Andean vs. European ancestry, controlling for gestational age and other characteristics. Another fruitful line of inquiry is likely to be determining whether persons with CMS or other altitude-associated problems experienced exaggerated hypoxia during prenatal or neonatal life. Finally, the comparison of high-altitude populations with respect to the frequencies of genes involved in oxygen sensing and physiologic response to hypoxia will be useful, once candidate genes have been identified.
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Parraguez, V. H., Atlagich, M., Díaz, R., Bruzzone, M. E., Behn, C., & Raggi, L. A. (2005) · Reproduction Fertility and Development · doi:10.1071/rd04060 · Cited by 40 · see citing works
Growth among Tibetans at high and low altitudes in India
Tripathy, V., & Gupta, R. (2007) · American Journal of Human Biology · doi:10.1002/ajhb.20638 · Cited by 37 · see citing works
“…comparing Tibetans, a high altitude native Asian population believed to be the best adapted at high altitude (Aldenderfer, 2003; Beall, 2000a,b, 2001; Moore, 2001; Moore et al., 2000), to people of similar ethnicContract grant sponsor: Indian Statistical Institute (Health and Disease project).”
BackgroundHigh Altitude Residence During Pregnancy Alters Cytokine and Catecholamine Levels
Coussons‐Read, M. E., Mazzeo, R. S., Whitford, M. H., Schmitt, M. P., MOORE, L. G., & Zamudio, S. (2002) · American Journal of Reproductive Immunology · doi:10.1034/j.1600-0897.2002.01078.x · Cited by 36 · see citing works
Intrauterine Growth Restriction
Hay, W. W., Wong, R. J., & Stevenson, D. K. (2001) · Cambridge University Press eBooks · doi:10.1017/9781009418034.010 · Cited by 37 · see citing works
Immediate and Long-Term Responses of the Carotid Body to High Altitude
Wilson, D. F., Roy, A., & Lahiri, S. (2005) · High Altitude Medicine & Biology · doi:10.1089/ham.2005.6.97 · Cited by 34 · see citing works
“Recent work by Moore et al. (2000) has shown that Tibetans, compared to other high-altitude residents, demonstrate higher ventilation and hypoxic ventilatory response.”
Gao, W., Gao, Y., Zhang, G., Song, L., Bingyong, S., & Shi, J.-Q. (2005) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cca.2005.05.006 · Cited by 25 · see citing works
Liu, J., Liu, Y., Ren, L.-H., Li, L., Wang, Z., Liu, S., Li, S.-Z., & Cao, T. (2016) · Scientific Reports · doi:10.1038/srep30500 · Cited by 21 · see citing works
Respiratory physiology of high-altitude anurans: 55 years of research on altitude and oxygen
Navas, C. A., & Chauí‐Berlinck, J. G. (2007) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2007.05.005 · Cited by 21 · see citing works
Limits on Inferring Genetic Adaptation to High Altitude in Himalayan and Andean Populations
Brutsaert, T. D. (2001) · High Altitude Medicine & Biology · doi:10.1089/152702901750265314 · Cited by 18 · see citing works
“Based in part on these and other contrasts between the two highland groups, Moore et al., suggest that Ti-betans are better adapted (Moore, 2000; Moore et al., 1992), which is essentially alternative 1 above.”
Zhang, L., Wang, Z., Chen, Y., Wang, X., Chen, Z., Feng, B., Zhu, Q., Nie, J., Dong, Y., Zhou, S., et al. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.03.025 · Cited by 18 · see citing works
Responses of Han Migrants Compared to Tibetans at High Altitude
Weitz, C. A., Liu, J., He, X., Chin, C., & Garruto, R. M. (2013) · American Journal of Human Biology · doi:10.1002/ajhb.22368 · Cited by 17 · see citing works
“It is ironic that a firmer consensus exists regarding differences between Tibetan and Andean responses to hypoxia (Beall, 2007; Brutsaert, 2008; Moore et al., 2000) than between Tibetans and Han Chinese—two groups that have lived together at high altitude for at least 40 years.”
BackgroundLin, Y., Li, B., Shi, X., Chen, Y., Pan, S., Lin, Z., Gu, Z., Hailer, F., Hu, L., & Zhan, X. (2025) · Nature Communications · doi:10.1038/s41467-025-64110-w · Cited by 15 · see citing works
“33; Supplementary Data 10), we further used RNA interference (RNAi) to check the effect of a blunted EPAS1 function on lipid metabolism.”
InfluentialGenetic and environmental adaptation in high altitude natives
Brutsaert, T. D. (2001) · Advances in experimental medicine and biology · doi:10.1007/978-1-4757-3401-0_10 · Cited by 13 · see citing works
Hufnagel, A., Grant, I. D., & Aiken, C. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.03.041 · Cited by 13 · see citing works
Malacrida, S., Katsuyama, Y., Droma, Y., Basnyat, B., Angelini, C. I., Ôta, M., & Danieli, G. A. (2007) · Annals of Human Genetics · doi:10.1111/j.1469-1809.2007.00358.x · Cited by 13 · see citing works
“Several lines of evidence suggest that Himalayan populations are genetically adapted to hypobaric hypoxia (Moore et al. 2000; Beall et al. 2002, 2004; Beall, 2003).”
BackgroundTaylor, L., Ashley, K., Jones, R. L., & Deddens, J. A. (2004) · American Journal of Industrial Medicine · doi:10.1002/ajim.20096 · Cited by 12 · see citing works
“, 1995], and higher percent hematocrit results in higher blood viscosity [Moore et al., 2000].”
BackgroundLiu, Y., Cui, W., Jin, X., Wang, K., Mei, S., Zheng, X.-K., & Zhu, B. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.880346 · Cited by 10 · see citing works
Huicho, L., Xing, G., Qualls, C., Rivera, M. C., Gamboa, J. L., Verma, A. M., & Appenzeller, O. (2008) · BMC Pediatrics · doi:10.1186/1471-2431-8-47 · Cited by 9 · see citing works
“In addition, Tibetans show lower frequency of intrauterine growth retardation, better neonatal oxygenation, lower pulmonary artery pressure and resistance, and lower frequency of chronic mountain sickness (CMS); a sudden loss of adaptation to their highland hypoxic abode appearing first in men in early midlife and in…”
Fabries, P. A., Drogou, C., Sauvet, F., Nespoulous, O., Erkel, M.-C., Marchandot, V., Bouaziz, W., Lepetit, B., Hornez, A., Malgoyre, A., et al. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.1000786 · Cited by 9 · see citing works
“In case of longterm maladaptation, chronic mountain sickness can also be explained by maladjusted chemosensitivity (9, 10).”
BackgroundResilience and Survival in Extreme Environments
Friedl, K. E., & Penetar, D. M. (2008) · CRC Press eBooks · doi:10.1201/9781420071788.ch7 · Cited by 9 · see citing works
Cross‐sectional study of electrocardiographic pattern in healthy children resident at high altitude
Huicho, L., & Niermeyer, S. (2007) · American Journal of Physical Anthropology · doi:10.1002/ajpa.20563 · Cited by 6 · see citing works
Oxygen sensing, anaesthesia and critical care: a narrative review
Slingo, M., & Pandit, J. J. (2021) · Anaesthesia · doi:10.1111/anae.15582 · Cited by 5 · see citing works
“Thus, it is hypothesised that having a relatively blunted hypoxic HIF response is protective, for example against chronic mountain sickness (a syndrome of excessive erythrocytosis, relative hypoventilation, pulmonary hypertension and right heart failure that is seen less commonly in these individuals) [41, 42].”
BackgroundPrevalencia de Policitemia Neonatal y Factores Asociados en Recién Nacidos
Barros, T. M. T., Ochoa, E., & Barros, J. M. T. (2021) · Revista Ecuatoriana de Pediatría · doi:10.52011/0090 · Cited by 2 · see citing works
Gutiérrez, F. Y. V. (2011) · Dialnet (Universidad de la Rioja) · Cited by 1 · see citing works
Wang, J. H., Xu, S. Z., Yong, Z., Bbu, C. F., Li, L. J. Y., & Duan, Y. Y. (2015) · Journal of Ultrasound in Medicine · doi:10.7863/ultra.34.6.1107 · Cited by 1 · see citing works
Características del período de adaptación del recién nacido en la altura
Ramos, W. R. V., Zirena, I. H., Bejar, M. C., & Castillo, J. D. (2009) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 1 · see citing works
Lumb, A. B. (2010) · Elsevier eBooks · doi:10.1016/b978-0-7020-2996-7.00017-9 · Cited by 1 · see citing works
Roach, R. C. (2001) · High Altitude Medicine & Biology · doi:10.1089/152702901750265404 · Cited by 1 · see citing works
Lumb, A. B. (2016) · Elsevier eBooks · doi:10.1016/b978-0-7020-6294-0.00015-0 · Cited by 1 · see citing works
A differential gene expression study in hypobaric hypoxia
Karar, J. (2008) · INFLIBNET
Characteristics of pregnancy, delivery and newborn children in the City of Huaraz,
Gonzales, G. F., Tapia, V., Cerna, J., Pajuelo, A., Muñoz, M. L., Carrillo, C., & Peñaranda, A. (2006)
Montesinos, D. L. C., & Molina, M. M. L. (2013)
BRAINSTEM GABAA RECEPTOR SHAPE THE RESPONSE AND ADAPTATION TO HYPOXIA
Hsieh, Y. (2007) · OhioLink ETD Center (Ohio Library and Information Network)
Gutiérrez, V., & Yessenia, F. (2011) · ACTA MEDICA PERUANA
Mechanisms Regulating Hypoxia Tolerance in Drosophila and Humans
Zhou, D., Azad, P., Stobdan, T., & Haddad, G. G. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813156-5.00022-4
Intrauterine Growth Restriction
Hay, W. W. (2004) · Nutrition and disease prevention · doi:10.1201/9780203997338.ch5
Tan, G. G. (2018) · Studies in human ecology and adaptation · doi:10.1007/978-3-319-76553-2_8
Advances in High-Altitude-Induced Kidney Injury: Mechanisms, Management, and Unmet Challenges
Qu, Y., Zhao, Z., Zhuang, J., Gu, S., Zhang, C., Maimaiti, R., Dong, X., Shi, W., & Jiang, H. (2026) · Kidney Medicine · doi:10.1016/j.xkme.2026.101457
Fan, H., Qi, S., Li, L., & Yan, Y. (2026) · Research Square · doi:10.21203/rs.3.rs-10427187/v1
- Authors
- Moore, L. G., Fernando Armaza, V., Villena, M., & Vargas, E.
- Affiliations
- University of Colorado Denver (US)
- Venue
- Advances in experimental medicine and biology
- Publisher
- Springer US
- Published
- 2002
- Volume
- 475
- Pages
- 45-62
- ISSN
- 0065-2598 (ISSN-L)
- OpenAlex
- W2125172962
- Cited by
- 64
- References
- 71
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 6
- FWCI
- 6.09
- Type
- book chapter
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Advances in experimental medicine and biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
- Physical Sciences › Environmental Science › Ecology › Physiological and biochemical adaptations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- high-altitude adaptation, Tibetan Plateau, Andean altiplano, hypoxia, chronic mountain sickness, fetal growth restriction, neonatal oxygenation, hypoxic ventilatory response, pulmonary artery pressure, hemoglobin levels, demographic history, genetic admixture
- MeSH terms
- Acclimatization, Altitude, Altitude Sickness, Animals, Hypoxia, Archaeology, Birth Weight, Blood Pressure, Female, Fetus, Hemoglobins, Humans, Infant, Newborn, Linguistics, Models, Biological, Oxygen, Paleontology, Pregnancy, Pregnancy Complications, Respiration, Selection, Genetic
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