The influence of age, sex, and exercise on autophagy, mitophagy, and lysosome biogenesis in skeletal muscle
Bibliographic record
Abstract
BACKGROUND: Aging decreases skeletal muscle mass and quality. Maintenance of healthy muscle is regulated by a balance between protein and organellar synthesis and their degradation. The autophagy-lysosome system is responsible for the selective degradation of protein aggregates and organelles, such as mitochondria (i.e., mitophagy). Little data exist on the independent and combined influence of age, biological sex, and exercise on the autophagy system and lysosome biogenesis. The purpose of this study was to characterize sex differences in autophagy and lysosome biogenesis in young and aged muscle and to determine if acute exercise influences these processes. METHODS: Young (4-6 months) and aged (22-24 months) male and female mice were assigned to a sedentary or an acute exercise group. Mitochondrial content, the autophagy-lysosome system, and mitophagy were measured via protein analysis. A TFEB-promoter-construct was utilized to examine Tfeb transcription, and nuclear-cytosolic fractions allowed us to examine TFEB localization in sedentary and exercised muscle with age and sex. RESULTS: Our results indicate that female mice, both young and old, had more mitochondrial protein than age-matched males. However, mitochondria in the muscle of females had a reduced respiratory capacity. Mitochondrial content was only reduced with age in the male cohort. Young female mice had a greater abundance of autophagy, mitophagy, and lysosome proteins than young males; however, increases were evident with age irrespective of sex. Young sedentary female mice had indices of greater autophagosomal turnover than male counterparts. Exhaustive exercise was able to stimulate autophagic clearance solely in young male mice. Similarly, nuclear TFEB protein was enhanced to a greater extent in young male, compared to young female mice following exercise, but no changes were observed in aged mice. Finally, TFEB-promoter activity was upregulated following exercise in both young and aged muscle. CONCLUSIONS: The present study demonstrates that biological sex influences mitochondrial homeostasis, the autophagy-lysosome system, and mitophagy in skeletal muscle with age. Furthermore, our data suggest that young male mice have a more profound ability to activate these processes with exercise than in the other groups. Ultimately, this may contribute to a greater remodeling of muscle in response to exercise training in males.
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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".