Metformin Preserves Mitochondrial Integrity at Old Age in Male Rats.
Bibliographic record
Abstract
Abstract Metformin is being deployed in clinical trials to ameliorate aging in older humans who do not have diabetes. In C. elegans, metformin treatment at old ages exacerbated mitochondrial dysfunction, led to respiratory failure, and shortened lifespan. Metformin is a commonly used, well-tolerated treatment for diabetes in older adults. Mitochondrial effects of metformin treatment in aged mammals has not been sufficiently investigated. We hypothesized that metformin treatment would not be toxic to older mammals. To define a therapeutic dose in aged hybrid rats, we evaluated two doses of metformin (0.1%, 0.75% of the diet) at 30-months of age. Body mass decreased at the 0.75% dose. Neither dose affected mortality between 30- and 34-months of age. We assessed mitochondrial quality, quantity, and function in aged rats treated with metformin at the 0.75% dose by measuring mitochondrial DNA copy number, deletion mutation frequency, and respirometry in skeletal muscle and heart. In skeletal muscle, we observed no effect of metformin on quadriceps mass, mtDNA copy number or deletion frequency. In the heart, metformin treated rats had higher mtDNA copy number, lower cardiac mass and no effect on deletion frequency. Metformin treatment resulted in lower mitochondrial complex I activity in both heart and quadriceps. Metformin did not compromise mitochondrial integrity, was well tolerated, and may have cardiac benefits to rats at old ages.
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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) | 0.001 | 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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".