The effects of age and exercise training on lysosomal adaptations within skeletal muscle
Bibliographic record
Abstract
Skeletal muscle mass comprises a large fraction (~40%) of the total human body mass, making it an essential contributor to overall physical health. Mitochondria are responsible for the metabolic status of skeletal muscle due to their ability to adapt to various physiological conditions. The aging population undergoes a loss of skeletal muscle mass, strength, and function, termed sarcopenia. The maintenance of a healthy mitochondrial pool is imperative for the preservation of muscle mass and metabolic health with age. The important removal of dysfunctional mitochondria happens via the process of mitophagy in which these organelles are tagged for degradation, engulfed and delivered to lysosomes, representing the vital role lysosomes play in the turnover of mitochondria. If lysosomes become defective with age, this can contribute to the accumulation of defective mitochondria. Thus, we have investigated lysosomes to understand their role in aging and exercise. We hypothesize that lysosome content will increase with age, but that lysosome proteolytic function will be diminished, and that exercise training will serve to restore this functionality in aged muscle. We studied these adaptations in skeletal muscle from young (5-7 months) and aged (21-23 months) mice following a 6-week voluntary wheel running (VWR) protocol compared to an untrained group. During the training protocol, the aged group ran significantly less than the young group. Despite this, training attenuated the aging-induced loss of muscle mass, especially in the predominantly slow-twitch soleus muscle. During an acute exhaustive bout of exercise, young and old trained groups ran significantly more time than untrained groups, indicating the effectiveness of the training to induce adaptative changes. Lysosomal protein yield was 2-fold greater in the aged, compared to the young cohorts, and this was accompanied by 1.5-fold, 2-fold and 2-fold increases in Lamp1, mature cathepsin D and precursor cathepsin B in aged muscle respectively. Lysosome proteolytic function, assessed in purified lysosomal fractions, was reduced by ~30 % in aged muscle. Remarkably, training improved lysosomal function in both young (1.3- fold) and old (1.5-fold) muscle. Thus, our results showed that aged mice have increased lysosomal protein content while displaying a more dysfunctional organelle pool. The chronic exercise protocol induced mitigation of these changes, illustrating the potential of improved clearance of dysfunctional cargo, including mitochondria, via enhanced proteolytic capacity of lysosomes, thereby improving muscle health with age. Supported by NSERC Canada. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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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".