Cystathionine gamma‐lyase/H <sub>2</sub> S signaling facilitates myogenesis under aging and injury condition
Bibliographic record
Abstract
Abstract Hydrogen sulfide (H 2 S) can be endogenously produced and belongs to the class of signaling molecules known as gasotransmitters. Cystathionine gamma‐lyase (CSE)‐derived H 2 S is implicated in the regulation of cell differentiation and the aging process, but the involvements of the CSE/H 2 S system in myogenesis upon aging and injury have not been explored. In this study, we demonstrated that CSE acts as a major H 2 S‐generating enzyme in skeletal muscles and is significantly down‐regulated in aged skeletal muscles in mice. CSE deficiency exacerbated the age‐dependent sarcopenia and cardiotoxin‐induced injury/regeneration in mouse skeletal muscle, possibly attributed to inefficient myogenesis. In contrast, supplement of NaHS (an H 2 S donor) induced the expressions of myogenic genes and promoted muscle regeneration in mice. In vitro, incubation of myoblast cells (C2C12) with H 2 S promoted myogenesis, as evidenced by the inhibition of cell cycle progression and migration, altered expressions of myogenic markers, elongation of myoblasts, and formation of multinucleated myotubes. Myogenesis was also found to upregulate CSE expression, while blockage of CSE/H 2 S signaling resulted in a suppression of myogenesis. Mechanically, H 2 S significantly induced the heterodimer formation between MEF2c and MRF4 and promoted the binding of MEF2c/MRF4 to myogenin promoter. MEF2c was S ‐sulfhydrated at both cysteine 361 and 420 in the C‐terminal transactivation domain, and blockage of MEF2c S ‐sulfhydration abolished the stimulatory role of H 2 S on MEF2c/MRF4 heterodimer formation. These findings support an essential role for H 2 S in maintaining myogenesis, presenting it as a potential candidate for the prevention of age‐related sarcopenia and treatment of muscle injury.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".