Blunted Autophagy and Heat Shock Responses in Peripheral Blood Mononuclear Cells of Elderly Adults During Prolonged, Extreme‐Heat Exposure

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With rising global temperatures and accompanying increases in the incidence and severity of extreme heat events, there are growing concerns about the impact of heat stress on human health. Increases in the activation of autophagy and the heat shock response are essential to cellular survival under stressful conditions, such as extreme heat. Accumulating evidence from various animal models suggests an age‐related decline in the autophagy and heat shock response pathways during heat stress; however, this has not yet been assessed in humans. We therefore sought to evaluate the hypothesis that the autophagy and heat shock response would be blunted in elderly compared to young adults following a prolonged heat exposure. To assess this hypothesis, peripheral blood mononuclear cells (PBMCs) were harvested from 10 young (23 [SD 3] years; 3 women) and 9 elderly adults (71 [SD 3] years; 2 women) prior to and following 9‐hours of resting exposure to extreme heat (40°C, ~15% relative humidity). Changes in microtubule associated protein 1 light chain 3 beta (LC3)‐II (indicative of autophagy) and heat shock protein 70 were analysed via Western blot, while their associated genes (LC3B and HSPA1A, respectively) were measured via quantitative reverse transcription polymerase chain reaction. All values were normalized to β‐actin and reported as fold changes relative to baseline. Core temperature (indexed by rectal temperature) was measured throughout the exposure. Data are presented as means and standard deviations (SD) and were compared between‐groups using unpaired (2 tailed) t‐tests (α=0.05). After 9‐h of heat exposure, the elevation in core temperature from baseline values were greater in the older (1.0°C [SD 0.3]) vs. young adults (0.6°C [SD 0.2]; p<0.01). Despite this, LC3‐II protein was lower in elderly (2.02 [SD 2.00]) when compared to young adults (4.45 [SD 5.93]; p=0.04). This was further revealed by a reduction in LC3B gene expression in elderly (1.39 [SD 0.39]) compared to young (2.57 [SD 3.78]; p=0.04) adults suggesting a blunting in the autophagic response during heat stress. In elderly, HSP70 protein and HSPA1A gene expression were both lower when compared to young (1.21 [SD 0.43] vs. 1.80 [SD 0.65]; p=0.02 and 1.58 [SD 1.64] vs. 2.88 [SD 4.29]; p=0.04, respectively) suggesting an age‐associated decline in the heat shock response. These preliminary findings demonstrate that despite greater elevations in core temperature, elderly adults experience blunting in both the autophagy and heat shock response during a prolonged extreme‐heat exposure.Support or Funding InformationCanadian Institutes of Health Research