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

摘要

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 (75?m), 24 investigators ascended from Kathmandu (1300?m) to Everest base camp (EBC 5300?m) over 13 days. Fourteen investigators climbed above EBC, eight of whom reached the summit (8848?m). 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±4.9?kg by expedition end; pConclusionsThe 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.