Parkin Overexpression Attenuates Aging‐related Muscle Atrophy in Mice
Bibliographic record
Abstract
One of the most significant changes associated with normal aging is a progressive loss of muscle mass and strength, a biological process termed sarcopenia. Solid experimental evidence indicates that mitochondrial dysfunctions (i) accumulate with muscle aging and (ii) are causally involved in sarcopenia. Recent findings suggest that mitophagy, the process in charge of the removal of damaged/dysfunctional mitochondria, is altered in aged muscle. Impaired mitophagy represents an attractive mechanism that could contribute to the accumulation of mitochondrial dysfunctions and sarcopenia. To test this hypothesis, we investigated the impact of Parkin overexpression in skeletal muscles of young and old mice. Parkin was overexpressed for 4 months in the tibialis anterior and gastrocnemius muscles of young (3 months old at the time of injection; 7 months old at the time of sacrifice) and late middle‐aged (18 months old at the time of injection; 22 months old at the time of sacrifice) mice using intramuscular injections of Adeno‐Associated Viruses (AAV). The expression of Parkin was driven in our viral construction by the muscle specific promoter MCK (Muscle Creatine Kinase). A control AAV, containing a sequence coding for the green fluorescent protein, was injected in the contralateral leg. As hypothesized, old control (GFP expressing) muscles displayed lower muscle weights and fiber cross‐sectional area as compared to their young adult counterparts. In both young and old animals Parkin‐overexpressing muscles displayed higher weights, fiber cross‐sectional area and complex II activity. In old mice, Parkin‐overexpressing muscles exhibited higher expression of complex II, complex IV and PGC‐1α. In line with these results, Parkin overexpressing muscles in aged animals exhibited a higher mitochondrial density on transmission electron micrographs. Old GFP expressing muscles displayed a higher 4‐hydroxynonenal content, a marker of oxidative stress, as compared to their young adult counterparts. Remarkably, Parkin overexpressing muscles in old mice had lower 4‐hydroxynonenal content vs their GFP counterparts. GFP expressing muscles of old mice also showed a higher type I collagen content as compared to their young adult counterparts, a sign of aging‐related fibrosis. Interestingly, Parkin overexpression in old mice was associated with lower type I collagen content. In conclusion, our results indicate that Parkin overexpression in old muscles attenuated sarcopenia, increased mitochondrial biogenesis and density, decreased oxidative stress and attenuated fibrosis. In young muscles, Parkin overexpression unexpectedly caused hypertrophy. Our results therefore suggest that Parkin might be an effective therapeutic target to counteract sarcopenia and to positively influence muscle function in young adults. Further studies are now required to dissect the mechanisms underlying the positive impacts of Parkin overexpression in young and aging skeletal muscles. Support or Funding Information This work was supported by the National sciences and Engineering Research Council of Canada and the Quebec Research Network on Aging
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".