The intensity-dependent effects of exercise and superimposing environmental heat stress on autophagy in peripheral blood mononuclear cells from older men

Autophagy is a vital cellular process, essential to maintaining cellular function during acute physiological stressors including exercise and heat stress. We previously showed that autophagy occurs during exercise in an intensity-dependent manner in peripheral blood mononuclear cells (PBMCs) from young men, with elevated responses in the heat. However, given autophagy declines with age, it is unclear whether a similar pattern of response occurs in older adults. Therefore, we evaluated autophagy and the cellular stress response [i.e., apoptosis, inflammation, and the heat shock response (HSR)] in PBMCs from 10 healthy older men [mean (SD): aged 70 yr (5)] in response to 30 min of semirecumbent cycling at low, moderate, and vigorous intensities [40, 55, and 70% maximal oxygen consumption (V̇o ), respectively] in a temperate (25°C) environment, with an additional vigorous-intensity bout (70% of V̇o ) performed in a hot environment (40°C). Responses were evaluated before and after exercise, as well as throughout a 6-h seated recovery period performed in the same environmental conditions as the respective exercise bout. Proteins were assessed via Western blot. Although we observed elevations in mean body temperature with each increase in exercise intensity, autophagy was only stimulated during vigorous-intensity exercise, where we observed elevations in LC3-II ( < 0.05). However, when the same exercise was performed in the heat, the LC3-II response was attenuated, which was accompanied by significant p62 accumulation ( < 0.05). Altogether, our findings demonstrate that older adults exhibit autophagic impairments when the same vigorous-intensity exercise is performed in hot environments, potentially underlying heat-induced cellular vulnerability in older men. We demonstrate that autophagic stimulation occurs in response to short-duration (30-min) vigorous-intensity exercise in peripheral blood mononuclear cells from older adults; however, no changes in autophagy occur during low- or moderate-intensity exercise. Moreover, older adults exhibit autophagic impairments when the same vigorous-intensity exercise is performed in hot ambient conditions. When paired with an attenuated heat shock response, as well as elevated apoptotic responses, older men may exhibit greater cellular vulnerability to exertional heat stress.