McCormick James J, Goulet Nicholas, King Kelli E, Fujii Naoto, Amano Tatsuro, Kenny Glen P
Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.
Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan.
Am J Physiol Regul Integr Comp Physiol. 2025 Jan 1;328(1):R90-R101. doi: 10.1152/ajpregu.00178.2024. Epub 2024 Nov 27.
The process of autophagy is vital in maintaining normal cellular function, especially during exposure to elevated states of physiological stress associated with exercise and hot ambient temperatures. Although prior observations are primarily limited to responses in males, the autophagic response to acute physiological stress in females represents a considerable knowledge gap. Therefore, we assessed autophagy and related pathways of cellular stress in peripheral blood mononuclear cells (PBMCs) from 20 healthy young [ = 10, mean (SD): aged 23 yr (3)] and older [ = 10, aged 69 yr (3)] females in response to 30 min of semi-recumbent high-intensity cycling exercise (70% of predetermined maximal oxygen consumption) in temperate (25°C) and hot (40°C) ambient conditions (15% relative humidity). Mean body temperature (rectal and skin) was measured throughout, whereas cellular responses were evaluated before and after exercise, including up to 6 h of seated recovery. Proteins associated with autophagy and related pathways were assessed via Western blot. Mean body temperature was elevated after exercise in both conditions, with significant elevations observed after exercise in the heat (all, ≤ 0.05). Although young females displayed signs of elevated autophagic activity [elevations in microtubule-associated light chain 3B (LC3)-II and beclin-2] in response to exercise performed in both temperate and hot ambient conditions (all, ≤ 0.05), responses were attenuated in older females. This was accompanied by elevations in chaperone-mediated autophagy in young but not in older females in response to exercise independent of ambient temperature. Our findings indicate exercise, with and without ambient heat exposure may stimulate the autophagic response in young but not in older females. We show for the first time that an acute bout (30 min) of high-intensity intensity exercise stimulates autophagy in young females irrespective of ambient heat exposure. However, older females did not display the same increase in autophagy as their younger counterparts when high-intensity exercise was performed in temperate or hot ambient conditions. Consequently, older females may be at an elevated risk of heat-induced cellular damage during exertional heat stress.
自噬过程对于维持正常细胞功能至关重要，尤其是在暴露于与运动和炎热环境温度相关的生理应激增强状态期间。尽管先前的观察主要限于男性的反应，但女性对急性生理应激的自噬反应存在相当大的知识空白。因此，我们评估了20名健康年轻女性（n = 10，平均[标准差]：年龄23岁[3岁]）和老年女性（n = 10，年龄69岁[3岁]）外周血单核细胞（PBMC）中的自噬及细胞应激相关途径，她们在温带（25°C）和炎热（40°C）环境条件（相对湿度15%）下进行30分钟半卧位高强度骑行运动（预定最大耗氧量的70%）。全程测量平均体温（直肠和皮肤），而细胞反应在运动前后进行评估，包括长达6小时的坐姿恢复。通过蛋白质印迹法评估与自噬及相关途径相关的蛋白质。在两种条件下运动后平均体温均升高，在炎热环境中运动后观察到显著升高（所有P≤0.05）。尽管年轻女性在温带和炎热环境条件下运动后均表现出自噬活性升高的迹象[微管相关轻链3B（LC3）-II和贝林2升高]（所有P≤0.05），但老年女性的反应减弱。这伴随着年轻女性而非老年女性在与环境温度无关的运动后伴侣介导的自噬升高。我们的研究结果表明，无论有无环境热暴露，运动可能会刺激年轻女性而非老年女性的自噬反应。我们首次表明，一次急性（30分钟）高强度运动无论环境热暴露如何都会刺激年轻女性的自噬。然而，在温带或炎热环境条件下进行高强度运动时，老年女性的自噬增加幅度不如年轻女性。因此，老年女性在运动性热应激期间可能面临热诱导细胞损伤风险升高的问题。
