Age-associated changes in excitation-contraction coupling are more prominent in ventricular myocytes from male rats than in myocytes from female rats
Bibliographic record
Abstract
We evaluated effects of age on components of excitation-contraction (EC) coupling in ventricular myocytes from male and female rats to examine sex differences in mechanisms responsible for age-related contractile dysfunction. Myocytes were isolated from anesthetized young adult (approximately 3 mo) and aged (approximately 24 mo) Fischer 344 rats. Ca(2+) concentrations and contractions were measured simultaneously (37 degrees C, 2 Hz). Fractional shortening declined with age in males (6.7 +/- 0.6% to 2.4 +/- 0.4%; P < 0.05), as did peak Ca(2+) transients (47.7 +/- 4.6 to 28.1 +/- 2.1 nM; P < 0.05) and Ca(2+) current densities (-7.7 +/- 0.7 to -6.2 +/- 0.5 pA/pF; P < 0.05). Although sarcoplasmic reticulum (SR) Ca(2+) content was similar regardless of age in males, EC coupling gain declined significantly with age to 55.8 +/- 7.8% of values in younger males. In contrast with results in males, contraction and Ca(2+) transient amplitudes were unaffected by age in females. Ca(2+) current density declined with age in females (-7.5 +/- 0.5 to -5.1 +/- 0.7 pA/pF; P < 0.05), but SR Ca(2+) content actually increased dramatically (49.0 +/- 7.5 to 147.3 +/- 28.5 nM; P < 0.05). Even so, EC coupling gain was not affected by age in female myocytes. Age also promoted hypertrophy of male myocytes more than female myocytes. Age and sex differences in EC coupling were largely maintained when conditioning pulse frequency was increased to 4 Hz. Contractions, Ca(2+) transients, and EC coupling gain were also smaller in young females than in young males. Thus age-dependent changes are more prominent in myocytes from males than females. Increased SR Ca(2+) content may compensate for reduced Ca(2+) current to preserve contractile function in aged females, which may limit the detrimental effects of age on cardiac contractile function.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".