Human cardiac ischemia‐reperfusion injury: Blunted stress response with age
Bibliographic record
Abstract
BACKGROUND AND AIM: Autophagy is a cytoprotective recycling mechanism, capable of digesting dysfunctional cellular components, and this process is associated with pro-survival outcomes. Autophagy may decline in the aging myocardium, thereby contributing to cardiac dysfunction. However, it remains to be established how autophagy responds to ischemia-reperfusion stress with age. METHODS: Samples from the right atrium were collected from young (≤50 years; n = 5) and aged (≥70 years; n = 11) patients before and immediately following cardioplegic arrest during coronary artery bypass grafting surgery, a model of human ischemia-reperfusion injury. RESULTS: Mitochondrial content, as assessed by a cohort of mitochondrial markers, exhibited an overall decrease in the aging myocardium (p = 0.01). In response to IR, COX-I (0.63 vs. 0.91, p = 0.01) increased in young, but not in aged patients (interaction effect p = 0.08). Reductions in LC3-I (0.48 vs. 0.28, p = 0.02) along with declines in TFEB and TFE3 (0.63 vs. 0.20, p = 0.05; 0.71 vs. 0.20, p = 0.01) were observed with age suggesting an impairment in the aged myocardium. Aged patients also displayed an inability to mount an appropriate response to IR compared to their young counterparts, specifically, increases in v-ATPase and NIX (1.06 vs 0.69, p = .01; 1.15 vs 0.69, p = .001) were not seen in the aged. CONCLUSION: Our data demonstrate a reduced cardiac mitochondrial content and a blunted mitochondrial response to ischemia with age, accompanied by a possible impairment in mitophagy. These findings support an age-associated inability of the atrial myocardium to mount appropriate adaptive responses to stress.
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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) | 0.002 | 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".