Regulation of Autophagy during Chronic Contractile Activity‐Induced Muscle Adaptations
Bibliographic record
Abstract
Autophagy is integral in the remodeling of skeletal muscle in response to various stimuli such as energy status, exercise, and/or other cellular stress. However, it currently remains obscure how autophagy is regulated in skeletal muscle over the course of training adaptations. In this study, we examined autophagic regulation in skeletal muscle of rats exposed to chronic contractile activity (CCA; 6 hours/day, 9V, 10 Hz continuous, 0.1 ms pulse duration) for 1, 3, and 7 days (N=8/each group). CCA resulted in muscle mitochondrial adaptation by day 7, as shown by the increase in PGC‐1α, a master regulator of mitochondrial biogenesis. This was supported by significant increases in other mitochondrial markers such as COX‐I and COX‐IV protein levels, as well as COX activity. Notably, the ratio of LC3 II/LC3 I, an indicator of autophagy, decreased by day 7 largely due to a significant increase in LC3 I. Furthermore, autophagic induction marker p62 appeared to be elevated on day 3 and returned to basal levels by day 7. We found that the lysosomal system is concomitantly upregulated in response to training whereby TFEB, a primary regulator of lysosomal biogenesis, increased 2‐fold by day 7 along with other lysosomal markers including LAMP1, LAMP2A, and MCOLN1. Our findings suggest that, in response to chronic exercise, autophagy is upregulated prior to mitochondrial adaptations, and the lysosomal system may play an important role in mediating autophagy and mitochondrial turnover in skeletal muscle during adaptations to a higher mitochondrial content. Support or Funding Information This work is supprted by Natural Sciences and Engineering Research Council of Canada (NSERC).
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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".