Age‐Associated Changes in Autophagy in Peripheral Blood Mononuclear Cells following Maximal Exercise: Preliminary Observations
Notice bibliographique
Résumé
Aging represents the progressive deterioration in the efficacy of cellular survival mechanisms, including the important mechanism of autophagy. Deficiencies in autophagic function, which occur with increasing age, may contribute to the development of many diseases, including neurodegeneration, cardiovascular diseases, and the development of various cancers. Thus, it is imperative to understand the regulation of autophagy in the context of human physiology. Of note, it is suggested that engaging in exercise represents an optimal strategy to improve autophagic function, which may help explain the many health benefits associated with regular exercise. During acute cellular stress, such as exercise, autophagy degrades misfolded or damaged proteins to provide the base constituents (i.e. amino acids) for cellular energy production. Although, until the past decade, few studies have examined the autophagic response to exercise in humans. We have recently demonstrated that exercise‐induced autophagy is intensity‐dependent, with greater intensities required to elicit an increase in autophagic flux, as indicated by elevated levels of microtubule‐associated protein 1 light chain 3 beta (LC3‐II). However, no known studies have evaluated the autophagic response to maximal exercise in humans, and it is unknown if this response is altered by aging. Therefore, we aimed to examine whether autophagy would increase in response to an acute (<15 min) incremental maximal exercise bout in peripheral blood mononuclear cells (PBMCs), and if this response would be altered in older adults. We evaluated the hypothesis that autophagy would increase in response to maximal exercise and that young adults would display greater elevations in autophagy than their older counterparts. To test this hypothesis, PBMCs were collected from 8 young (mean [SD], 20 [2.1] years; 4 women, 4 men) and 8 older (66 [5.5] years; 4 women, 4 men) adults before and immediately after a graded maximal exercise test performed on a semi‐recumbent cycle ergometer. The autophagic marker LC3‐II was assessed by Western blotting, which was normalized to β‐actin (an internal loading control) and reported as a fold change relative to its respective baseline. Data were analyzed using unpaired t‐tests with an alpha set at 0.05. Peak oxygen consumption (VO 2peak ) was significantly higher in young (41.6 [10.3] ml/kg/min) compared to older (30.3 [6.6] ml/kg/min) adults (p=0.02). Immediately following the maximal exercise bout, an increase in LC3‐II was observed in both young (1.64 [0.45], p=0.005) and older (1.21, [0.24] p=0.048) adults. When comparing between groups, the relative increase in LC3‐II was significantly greater (+27%) in young compared to older adults (p=0.03). Taken together, our preliminary findings show that autophagy is elevated in response to maximal exercise in young and older adults, albeit to a lesser extent in older adults, suggesting an impaired ability to respond to cellular stress. Further research is necessary to understand the mechanisms underlying age‐related impairments in autophagy in older adults and if these responses can be restored.
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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 ».