Nutrition 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.
Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle on Tyne NE4 5PL, UK.
Redox Biol. 2017 Oct;13:60-68. doi: 10.1016/j.redox.2017.05.004. Epub 2017 May 8.
Sarcopenia 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.
After 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.
Participants 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.
The 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.
肌少症是指骨骼肌的非自愿性损失，是身体残疾/死亡率的预测指标。其发病机制尚不清楚，尽管已经提出了缺氧信号改变、氧化应激、脂肪因子和炎症介质的作用。在高海拔缺氧的情况下也会发生肌少症。因此，我们利用来自 Caudwell Xtreme Everest 探险的数据，分析了缺氧引起的身体成分变化的程度，并确定了与去脂体重（FFM）和脂肪量（FM）损失相关的潜在途径。
在伦敦（75 米）进行基线测试后，24 名研究人员从加德满都（1300 米）攀登到珠穆朗玛峰大本营（EBC5300 米），历时 13 天。14 名研究人员攀登到 EBC 以上，其中 8 人到达了顶峰（8848 米）。在基线、攀登期间以及抵达 EBC 后的一周、六周和八周进行评估。通过生物电阻抗法测量身体成分（FM、FFM、总身体水分、细胞内和细胞外水分）的变化。同时测量了一氧化氮和氧化应激的生物标志物以及脂肪因子、炎症、代谢和血管标志物。
参与者的体重显著减轻（探险结束时为 7.3±4.9kg；p<0.001），但变化程度不同。观察到 FM 和 FFM 均持续减少，八周后，FFM 损失比例比 FM 损失比例高 48%（p<0.008）。蛋白质羰基（p<0.001）的变化与 FM 减少有关，而 4-羟基壬烯醛（p<0.001）和 IL-6（p<0.001）与 FFM 减少有关。GLP-1（r=-0.45，p<0.001）和亚硝酸盐（r=-0.29，p<0.001）浓度变化与 FFM 减少有关。在多变量模型中，GLP-1、胰岛素和亚硝酸盐是 FFM 损失的显著预测因子，而蛋白质羰基则是 FM 损失的预测因子。
GLP-1 和亚硝酸盐作为缺氧对 FFM 影响的介质的假设作用是一个有趣的发现。如果得到证实，针对这些途径的营养和药理学干预可能为肌少症的预防和治疗提供新途径。
