Regulation of the NAD <sup>+</sup> ‐dependent histone deacetylase Sirt1 in conditions of muscle use and disuse
Bibliographic record
Abstract
Caloric restriction promotes longevity in mammals. This effect is mediated by the NAD + ‐dependent histone deacetylase Sirt1, which is sensitive to metabolic alterations and interacts with the regulatory protein of mitochondrial biogenesis PGC‐1α. Conditions of muscle use and disuse such as endurance training and denervation are known to produce alterations in mitochondrial biogenesis as well as energy metabolism. To determine whether Sirt1 is regulated under those conditions, Sirt1 deacetylase activity was evaluated in muscles of rats subjected to chronic electrical stimulation for 7 days (10 Hz; 3 hrs/day), or denervation for 14 days. Mitochondrial biogenesis was determined by measuring the protein expression of PGC‐1α and cytochrome c, and COX enzyme activity. Sirt1 activity was measured using a fluorimetric deacetylation assay and its reliability was assessed as a function of sample protein concentration, incubation time, and inhibitor (nicotinamide) concentration. In chronically‐stimulated extensor digitorum longus (EDL) muscle, PGC‐1α, cytochrome c and COX enzyme activity were increased by 30–50% compared to non‐stimulated muscle. In denervated EDL, those markers of mitochondrial biogenesis were decreased to the same extent (30–50%) compared to the control muscle. In contrast, Sirt1 activity was increased by 20% and 76% in chronically‐stimulated and denervated EDL, respectively. Our data suggest that 1) SIRT1 and PGC‐1α expression are independently regulated, and 2) mitochondrial biogenesis and SIRT1 function are involved in separate metabolic pathways in conditions of muscle use and disuse. Support from CIHR.
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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) | 0.001 | 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".