Characterizing Autophagic And Apoptotic Responses To Cold Stress In Healthy, Young And Older Men
Bibliographic record
Abstract
Cold stress can compromise cellular function by modifying autophagic activity, which disrupts cellular homeostasis and promotes apoptosis (cell death). This response may be exacerbated in older adults due to an age-related reduction in autophagy, leading to greater vulnerability for cold-related injuries, depending on the level of cold stress. PURPOSE: In this study, we evaluated the effect of different levels of cold stress induced by cold water immersion on autophagic activity and apoptosis in young and older men. METHODS: On separate days, young (n = 9, mean [SD]: 23 [4] years) and older (n = 6, 62 [3] years) healthy, habitually active men were immersed in cold water regulated to induce a mild or severe cold stress by a sustained decrease in core (esophageal) temperature (Tco) of 0.5 and 1.0 °C below baseline resting levels for 30 min, respectively. Participants were rewarmed with warm (39 °C) water to baseline Tco and transferred to a thermoneutral room (23 °C) for a 3-h recovery. Blood samples were collected during baseline, end-cold exposure, and end-recovery to isolate peripheral blood mononuclear cells. Proteins associated with autophagy (LC3-II) and apoptosis (cleaved-caspase-3) were assessed via Western blot, normalized to β-actin, and reported as relative quantity (RQ) from baseline. Data were compared using a two-way ANOVA with Fisher’s LSD post-hoc (α = 0.05). RESULTS: Following mild cold exposure and recovery, LC3-II increased in young men (1.51RQ [0.54] and 1.69RQ [0.68], respectively; both p ≤ 0.028), but not in older men (1.07RQ [0.27] and 1.19RQ [0.70], respectively; both p ≥ 0.534). Following the severe cold exposure, however, caspase-3 increased in both the young (1.57RQ [0.45]; p = 0.033) and older (2.52RQ [1.84]; p = 0.025) men, albeit with no change in LC3-II. Further, LC3-II was higher during the mild cold exposure in young compared to older men (p = 0.027) and caspase-3 was greater during the severe cold exposure in older compared to young men (p = 0.044). CONCLUSION: We demonstrated that mild cold stress stimulates autophagic cytoprotection in young, but not older men. Conversely, severe cold exposure blunts autophagic activity, with greater apoptotic signaling in older compared to young men. FUNDING: National Sciences and Engineering Research Council
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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".