Enhanced Mitochondrial Turnover in Aged Human Right Atrial Tissue
Bibliographic record
Abstract
Age is one of the greatest risk factors for cardiovascular disease, which is the leading cause of death in the developed world. Therefore, the maintenance of cardiac health throughout the lifespan is of the upmost importance. Aging is associated with a plethora of biochemical and metabolic alterations, many of which converge on the mitochondrion. As a highly oxidative tissue, mitochondria supply roughly 95% of all ATP required in the myocardium. This reliance on mitochondria underscores the importance of maintaining the quality of these organelles, especially with age, however little is known about how age effects quality control mechanisms in the human heart. We hypothesized that the removal of mitochondria through mitochondrial specific autophagy, or mitophagy, would be impaired in aged human cardiac tissue. To evaluate mitochondrial quality control, samples of right atria were collected from young (≤50 years) and aged (≥70 years) patients undergoing coronary artery bypass surgery (CABG). Tissue was collected prior to and immediately following surgery, providing a useful model of ischemia‐reperfusion injury. Patients were matched for hyperention and dyslipidemia, as well as prescribed medications such as statins, and ACE inhibitors. Exclusion criteria included smoking, a prior stroke or myocardial infarction, or other comorbidities (e.g. diabetes, cancer). Mitochondrial content as indicated by various markers such as COX IV, VDAC, and UQCRC2 was reduced in the aged samples, however a modest 1.2‐fold increase in Citrate Synthase was observed, suggesting age‐associated compositional changes. The upstream marker of autophagy Beclin‐1 and the transcriptional regulators TFEB and TFE3 did not change with age, suggesting that aging does not affect the drive for autophagy. Despite this, constituents of the autophagosome p62 and LC3‐II were reduced by 20% and 30%, respectively, in the aged samples, indicative of increased autophagy flux. The mitophagy marker Parkin displayed a trend to decrease with age, suggesting a decline in the signaling for mitophagy. The lysosomal marker Cathepsin D was unaffected by age in cardiac muscle, but the lysosomal calcium channel Mucolipin‐1 increased in aged atrial muscle by 2‐fold. Analysis of post‐CABG samples indicated marked elevations in HSP70 and Caspase‐3 protein compared to pre‐CABG values. This was only evident in the atria of aged individuals. Our data suggest that increased mitophagy flux could account for the reductions in mitochondrial markers in aged atria, and that CABG can induce a stress response leading to apoptosis signaling that is more prominent with age. Support or Funding Information Supported by NSERC Canada.
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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 | 0.001 | 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".