Long-term calorie restriction reduces proton leak and hydrogen peroxide production in liver mitochondria
Bibliographic record
Abstract
Calorie restriction (CR) without malnutrition increases maximal life span in diverse species. It has been proposed that reduction in energy expenditure and reactive oxygen species (ROS) production could be a mechanism for life span extension with CR. As a step toward testing this theory, mitochondrial proton leak, H2O2 production, and markers of oxidative stress were measured in liver from FBNF1 rats fed control or 40% CR diets for 12 or 18 mo. CR was initiated at 6 mo of age. Proton leak kinetics curves, generated from simultaneous measures of oxygen consumption and membrane potential, indicated a decrease in proton leak after 18 mo of CR, while only a trend toward a proton leak decrease was observed after 12 mo. Significant shifts in phosphorylation and substrate oxidation curves also occurred with CR; however, these changes occurred in concert with the proton leak changes. Metabolic control analysis indicated no difference in the overall pattern of control of the oxidative phosphorylation system between control and CR animals. At 12 mo, no significant differences were observed between groups for H2O2 production or markers of oxidative stress. However, at 18 mo, protein carbonyl content was lower in CR animals, as was H2O2 production when mitochondria were respiring on either succinate alone or pyruvate plus malate in the presence of rotenone. These results indicate that long-term CR lowers mitochondrial proton leak and H2O2 production, and this is consistent with the idea that CR may act by decreasing energy expenditure and ROS production.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".