Impaired autophagy following ex vivo heating at physiologically relevant temperatures in peripheral blood mononuclear cells from elderly adults.

ABSTRACT

With the increasing threat of climate change and the accompanying rise in the frequency and severity of extreme heat events, there are growing health concerns for heat-vulnerable elderly adults. Elderly adults are at increased risk of developing heat-related injuries, in part due to age-related declines in thermoregulatory and cellular function. Regarding the latter, the process of autophagy is activated as a cellular protective mechanism to counter heat-induced stress, but the extent that heat stress activates autophagy in elderly adults is not known. Further, the interplay between autophagy, the heat shock response (HSR), the acute inflammatory response, and apoptosis remains poorly understood in elderly adults. Therefore, the purpose of this study was to examine changes in autophagy, the HSR, inflammation, and apoptosis following increasing levels of ex vivo heat stress representative of physiologically relevant increases in body core temperatures (37-41 °C). Whole blood from 20 elderly adults (72 ± 4 years; 14 men, 6 women) was heated (via water immersion) to temperatures representative of normal resting conditions (normothermia; 37 °C), in addition to moderate and severe heat stress conditions (39, and 41 °C, respectively) for 90 min. Peripheral blood mononuclear cells (PBMC) were isolated and protein markers of autophagy, the HSR, acute inflammation, and apoptosis were examined. No significant increases in markers of autophagy or the HSR were observed following any temperature condition. However, an increase in acute inflammation was observed above baseline following moderate heat stress (39 °C), with further increases in inflammation and apoptosis observed during severe heat stress (41 °C). Our findings indicate that PBMCs from elderly adults do not exhibit increases in autophagy or the HSR following severe heat stress, potentially contributing to the elevated risk of cellular dysfunction seen in elderly adults during heat stress.