Autophagy in Peripheral Blood Mononuclear Cells of Older Adults Following Day‐Long Exposure to Increasing Levels of Ambient Heat Stress: Preliminary Observations
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».