Blunted Autophagy and Heat Shock Responses in Peripheral Blood Mononuclear Cells of Elderly Adults During Prolonged, Extreme‐Heat Exposure
Bibliographic record
Abstract
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 Information Canadian Institutes of Health Research
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".