Evidence map›Paper›PMID 28570949›Full record

ArticleRedox biology2017

Does hypoxia play a role in the development of sarcopenia in humans? Mechanistic insights from the Caudwell Xtreme Everest Expedition.

Liesl Wandrag, Mario Siervo, Heather L Riley, Maryam Khosravi, Bernadette O Fernandez, Carl A Leckstrom, Daniel S Martin, Kay Mitchell, Denny Z H Levett, Hugh E Montgomery and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 1 country.

Liesl WandragNutrition and Dietetic Research Group, Department of Investigative Medicine, Imperial College London, UK; University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, 170 Tottenham Court Road, London W1T 7HA, UK.
Mario SiervoHuman Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle on Tyne NE4 5PL, UK.
Heather L RileyWarwick Systems Biology Centre and Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Maryam KhosraviUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, 170 Tottenham Court Road, London W1T 7HA, UK; Department of Cell and Developmental Biology, Division of Biosciences, University College London, WC1B 6BT, UK.
Bernadette O FernandezWarwick Systems Biology Centre and Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK; Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
Carl A LeckstromWarwick Systems Biology Centre and Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Daniel S MartinUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, 170 Tottenham Court Road, London W1T 7HA, UK; Division of Surgery and Interventional Science, University College London, 9th Floor, Royal Free Hospital, London NW3 2QG, UK.
Kay MitchellUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, 170 Tottenham Court Road, London W1T 7HA, UK; University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton SO16 6YD, UK.
Denny Z H LevettUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, 170 Tottenham Court Road, London W1T 7HA, UK; University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton SO16 6YD, UK; Southampton NIHR Respiratory Biomedical Research Unit, UK.
Hugh E MontgomeryUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, 170 Tottenham Court Road, London W1T 7HA, UK.
Monty G MythenUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, 170 Tottenham Court Road, London W1T 7HA, UK.
Michael A StroudUniversity Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton SO16 6YD, UK.
Michael P W GrocottUniversity College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, 170 Tottenham Court Road, London W1T 7HA, UK; Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton SO16 6YD, UK; Southampton NIHR Respiratory Biomedical Research Unit, UK.
Martin FeelischWarwick Systems Biology Centre and Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK; Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton SO16 6YD, UK; Southampton NIHR Respiratory Biomedical Research Unit, UK. Electronic address: m.feelisch@soton.ac.uk.
Caudwell Xtreme Everest Research Group
University Hospital Southampton NHS Foundation Trust · GBUniversity College London · GBUniversity of Warwick · GBNewcastle University · GBThe Royal Free Hospital · GB

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council G0701115Medical Research Council G1001536Medical Research Council MR/N007921/1
6 · The paper itself

Abstract

objectivesSarcopenia refers to the involuntary loss of skeletal muscle and is a predictor of physical disability/mortality. Its pathogenesis is poorly understood, although roles for altered hypoxic signaling, oxidative stress, adipokines and inflammatory mediators have been suggested. Sarcopenia also occurs upon exposure to the hypoxia of high altitude. Using data from the Caudwell Xtreme Everest expedition we therefore sought to analyze the extent of hypoxia-induced body composition changes and identify putative pathways associated with fat-free mass (FFM) and fat mass (FM) loss.

methodsAfter baseline testing in London (75m), 24 investigators ascended from Kathmandu (1300m) to Everest base camp (EBC 5300m) over 13 days. Fourteen investigators climbed above EBC, eight of whom reached the summit (8848m). Assessments were conducted at baseline, during ascent and after one, six and eight week(s) of arrival at EBC. Changes in body composition (FM, FFM, total body water, intra- and extra-cellular water) were measured by bioelectrical impedance. Biomarkers of nitric oxide and oxidative stress were measured together with adipokines, inflammatory, metabolic and vascular markers.

resultsParticipants lost a substantial, but variable, amount of body weight (7.3±4.9kg by expedition end; p<0.001). A progressive loss of both FM and FFM was observed, and after eight weeks, the proportion of FFM loss was 48% greater than FM loss (p<0.008). Changes in protein carbonyls (p<0.001) were associated with a decline in FM whereas 4-hydroxynonenal (p<0.001) and IL-6 (p<0.001) correlated with FFM loss. GLP-1 (r=-0.45, p<0.001) and nitrite (r=-0.29, p<0.001) concentration changes were associated with FFM loss. In a multivariate model, GLP-1, insulin and nitrite were significant predictors of FFM loss while protein carbonyls were predicted FM loss.

conclusionsThe putative role of GLP-1 and nitrite as mediators of the effects of hypoxia on FFM is an intriguing finding. If confirmed, nutritional and pharmacological interventions targeting these pathways may offer new avenues for prevention and treatment of sarcopenia.

Indexed as

AltitudeAdultBiomarkersBody CompositionFemaleGlucagon-Like Peptide 1HumansHypoxiaMaleMiddle AgedNitritesOxidative StressSarcopeniaBiomarkersGlucagon-Like Peptide 1NitritesGlucagon-like peptide-1Hypobaric hypoxiaHypoxemiaInflammationInsulinInterleukin-6Lean body massNitriteOxidative stress

Identifiers

PMID28570949
PMCPMC5451185
OpenAlexW2613154641

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.