Metabolic basis to Sherpa altitude adaptation

James A. Horscroft; Aleksandra O. Kotwica; Verena Laner; James A. West; Philip J. Hennis; Denny Z.H. Levett; David J. Howard; Bernadette O. Fernandez; Sarah L. Burgess; Zsuzsanna Ament; Edward T. Gilbert-Kawai; André Vercueil; Blaine D. Landis; Kay Mitchell; Monty G. Mythen; Cristina Branco; Randall S. Johnson; Martin Feelisch; Hugh E. Montgomery; Julian L. Griffin; Michael P.W. Grocott; Erich Gnaiger; Daniel S. Martin; Andrew J. Murray

doi:10.1073/pnas.1700527114

Metabolic basis to Sherpa altitude adaptation

James A. Horscroft, Aleksandra O. Kotwica, Verena Laner, James A. West, Philip J. Hennis, Denny Z.H. Levett, David J. Howard, Bernadette O. Fernandez, Sarah L. Burgess, Zsuzsanna Ament, Edward T. Gilbert-Kawai, André Vercueil, Blaine D. Landis, Kay Mitchell, Monty G. Mythen, Cristina Branco, Randall S. Johnson, Martin Feelisch, Hugh E. Montgomery, Julian L. GriffinMichael P.W. Grocott, Erich Gnaiger, Daniel S. Martin, Andrew J. Murray^*

^*Corresponding author for this work

Peninsula Medical School

Research output: Contribution to journal › Article › peer-review

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Abstract

Significance A relative fall in tissue oxygen levels (hypoxia) is a common feature of many human diseases, including heart failure, lung diseases, anemia, and many cancers, and can compromise normal cellular function. Hypoxia also occurs in healthy humans at high altitude due to low barometric pressures. Human populations resident at high altitude in the Himalayas have evolved mechanisms that allow them to survive and perform, including adaptations that preserve oxygen delivery to the tissues. Here, we studied one such population, the Sherpas, and found metabolic adaptations, underpinned by genetic differences, that allow their tissues to use oxygen more efficiently, thereby conserving muscle energy levels at high altitude, and possibly contributing to the superior performance of elite climbing Sherpas at extreme altitudes.

Original language	English
Pages (from-to)	6382-6387
Number of pages	0
Journal	Proceedings of the National Academy of Sciences
Volume	114
Issue number	24
Early online date	22 May 2017
DOIs	https://doi.org/10.1073/pnas.1700527114
Publication status	Published - 13 Jun 2017

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Horscroft et al-2017-PNAS-AM-3

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Horscroft, J. A., Kotwica, A. O., Laner, V., West, J. A., Hennis, P. J., Levett, D. Z. H., Howard, D. J., Fernandez, B. O., Burgess, S. L., Ament, Z., Gilbert-Kawai, E. T., Vercueil, A., Landis, B. D., Mitchell, K., Mythen, M. G., Branco, C., Johnson, R. S., Feelisch, M., Montgomery, H. E., ... Murray, A. J. (2017). Metabolic basis to Sherpa altitude adaptation. Proceedings of the National Academy of Sciences, 114(24), 6382-6387. https://doi.org/10.1073/pnas.1700527114

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title = "Metabolic basis to Sherpa altitude adaptation",

abstract = "Significance A relative fall in tissue oxygen levels (hypoxia) is a common feature of many human diseases, including heart failure, lung diseases, anemia, and many cancers, and can compromise normal cellular function. Hypoxia also occurs in healthy humans at high altitude due to low barometric pressures. Human populations resident at high altitude in the Himalayas have evolved mechanisms that allow them to survive and perform, including adaptations that preserve oxygen delivery to the tissues. Here, we studied one such population, the Sherpas, and found metabolic adaptations, underpinned by genetic differences, that allow their tissues to use oxygen more efficiently, thereby conserving muscle energy levels at high altitude, and possibly contributing to the superior performance of elite climbing Sherpas at extreme altitudes.",

author = "Horscroft, {James A.} and Kotwica, {Aleksandra O.} and Verena Laner and West, {James A.} and Hennis, {Philip J.} and Levett, {Denny Z.H.} and Howard, {David J.} and Fernandez, {Bernadette O.} and Burgess, {Sarah L.} and Zsuzsanna Ament and Gilbert-Kawai, {Edward T.} and Andr{\'e} Vercueil and Landis, {Blaine D.} and Kay Mitchell and Mythen, {Monty G.} and Cristina Branco and Johnson, {Randall S.} and Martin Feelisch and Montgomery, {Hugh E.} and Griffin, {Julian L.} and Grocott, {Michael P.W.} and Erich Gnaiger and Martin, {Daniel S.} and Murray, {Andrew J.}",

year = "2017",

month = jun,

day = "13",

doi = "10.1073/pnas.1700527114",

language = "English",

volume = "114",

pages = "6382--6387",

journal = "Proceedings of the National Academy of Sciences",

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Horscroft, JA, Kotwica, AO, Laner, V, West, JA, Hennis, PJ, Levett, DZH, Howard, DJ, Fernandez, BO, Burgess, SL, Ament, Z, Gilbert-Kawai, ET, Vercueil, A, Landis, BD, Mitchell, K, Mythen, MG, Branco, C, Johnson, RS, Feelisch, M, Montgomery, HE, Griffin, JL, Grocott, MPW, Gnaiger, E, Martin, DS & Murray, AJ 2017, 'Metabolic basis to Sherpa altitude adaptation', Proceedings of the National Academy of Sciences, vol. 114, no. 24, pp. 6382-6387. https://doi.org/10.1073/pnas.1700527114

TY - JOUR

T1 - Metabolic basis to Sherpa altitude adaptation

AU - Horscroft, James A.

AU - Kotwica, Aleksandra O.

AU - Laner, Verena

AU - West, James A.

AU - Hennis, Philip J.

AU - Levett, Denny Z.H.

AU - Howard, David J.

AU - Fernandez, Bernadette O.

AU - Burgess, Sarah L.

AU - Ament, Zsuzsanna

AU - Gilbert-Kawai, Edward T.

AU - Vercueil, André

AU - Landis, Blaine D.

AU - Mitchell, Kay

AU - Mythen, Monty G.

AU - Branco, Cristina

AU - Johnson, Randall S.

AU - Feelisch, Martin

AU - Montgomery, Hugh E.

AU - Griffin, Julian L.

AU - Grocott, Michael P.W.

AU - Gnaiger, Erich

AU - Martin, Daniel S.

AU - Murray, Andrew J.

PY - 2017/6/13

Y1 - 2017/6/13

N2 - Significance A relative fall in tissue oxygen levels (hypoxia) is a common feature of many human diseases, including heart failure, lung diseases, anemia, and many cancers, and can compromise normal cellular function. Hypoxia also occurs in healthy humans at high altitude due to low barometric pressures. Human populations resident at high altitude in the Himalayas have evolved mechanisms that allow them to survive and perform, including adaptations that preserve oxygen delivery to the tissues. Here, we studied one such population, the Sherpas, and found metabolic adaptations, underpinned by genetic differences, that allow their tissues to use oxygen more efficiently, thereby conserving muscle energy levels at high altitude, and possibly contributing to the superior performance of elite climbing Sherpas at extreme altitudes.

AB - Significance A relative fall in tissue oxygen levels (hypoxia) is a common feature of many human diseases, including heart failure, lung diseases, anemia, and many cancers, and can compromise normal cellular function. Hypoxia also occurs in healthy humans at high altitude due to low barometric pressures. Human populations resident at high altitude in the Himalayas have evolved mechanisms that allow them to survive and perform, including adaptations that preserve oxygen delivery to the tissues. Here, we studied one such population, the Sherpas, and found metabolic adaptations, underpinned by genetic differences, that allow their tissues to use oxygen more efficiently, thereby conserving muscle energy levels at high altitude, and possibly contributing to the superior performance of elite climbing Sherpas at extreme altitudes.

U2 - 10.1073/pnas.1700527114

DO - 10.1073/pnas.1700527114

M3 - Article

SN - 0027-8424

VL - 114

SP - 6382

EP - 6387

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

IS - 24

ER -

Metabolic basis to Sherpa altitude adaptation

Abstract

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