Autophagy in Peripheral Blood Mononuclear Cells of Older Adults Following Day‐Long Exposure to Increasing Levels of Ambient Heat Stress: Preliminary Observations
Bibliographic record
Abstract
Autophagy is a cytoprotective mechanism that can preserve cellular function during exposure to different physiological stressors, including heat stress. Age‐related decline in autophagy has been demonstrated in cell and animal models, with our recent work indicating no discernible activation of autophagy in human peripheral blood mononuclear cells (PBMCs) exposed to ex vivo heating (simulating core temperatures of 39 and 41˚C). Further in our on‐going work, we have observed impaired autophagy in older adults that is accompanied by augmented thermal strain during day‐long (9 h) exposure to extreme heat (40°C ambient temperature). However, it remains unclear if this inhibition of autophagy is influenced by the severity of heat stress (<40°C ambient temperature). Therefore, the purpose of this preliminary observation was to evaluate autophagy in older adults during day‐long environmental exposure from no heat stress (22°C ambient temperature) to moderate heat stress (36°C). We evaluated the hypothesis that older adults would demonstrate increased autophagic activity as a function of increasing environmental heat stress. As part of a larger study evaluating the efficacy of indoor temperature limits to safeguard health during extreme heat events, PBMCs were harvested on separate days from 7 older adults (aged 66‐78 years) prior to and following 8 h of resting exposure to four different ambient conditions; 22, 26, 31, and 36°C (all 45% relative humidity, <0.3 m/sec air flow). These conditions reflect the spectrum of environmental temperatures experienced indoors during the summer period in temperate continental climates. Rectal temperature (T re ) was measured throughout and reported as the change from the baseline and final 5 min of each 8 h exposure. Autophagic activity was assessed via Western blot by analyzing changes in Unc‐51 like autophagy activating kinase (ULK‐1) and microtubule associated protein 1 light chain 3 beta (LC3‐II). These data were normalized to β‐actin and reported as the difference in fold‐change from baseline relative to the coolest condition (22°C). Data were compared using a one‐way repeated measures ANOVA with Fisher's LSD post‐hoc analysis. The change in T re increased from 22°C to 26, 31, and 36°C (mean ± SD, 0.0 ± 0.3, 0.2 ± 0.3, 0.9 ± 0.4, and 1.1 ± 0.4°C, respectively). ULK‐1 significantly increased during the 26°C (mean diff. from 22°C [95% CI]; 0.42 [0.05, 0.78], p=0.03) and 31°C conditions (0.43 [0.07, 0.80], p=0.02), but declined following the 36°C condition (‐0.40 [‐0.76, ‐0.04], p=0.03). There were no significant changes in LC3‐II during these conditions (p=0.16). Our preliminary data indicates that autophagic activity is unabated following 8‐h exposure up to 31°C (via an increase in ULK‐1), however, there was no impact on LC3‐II. At higher ambient temperatures (36°C), a decrease in ULK‐1 suggests greater cellular vulnerability may occur in older adults in prolonged ambient conditions above 31°C. Further investigation is required to evaluate the underlying source regarding the absence of an LC3‐II response.
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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".