Mitochondrial Mechanisms of Neuromuscular Junction Degeneration with Aging
Bibliographic record
Abstract
Skeletal muscle deteriorates with aging, contributing to physical frailty, poor health outcomes, and increased risk of mortality. Denervation is a major driver of changes in aging muscle. This occurs through transient denervation-reinnervation events throughout the aging process that remodel the spatial domain of motor units and alter fiber type. In advanced age, reinnervation wanes, leading to persistent denervation that accelerates muscle atrophy and impaired muscle contractility. Alterations in the muscle fibers and motoneurons are both likely involved in driving denervation through destabilization of the neuromuscular junction. In this respect, mitochondria are implicated in aging and age-related neurodegenerative disorders, and are also likely key to aging muscle changes through their direct effects in muscle fibers and through secondary effects mediated by mitochondrial impairments in motoneurons. Indeed, the large abundance of mitochondria in muscle fibers and motoneurons, that are further concentrated on both sides of the neuromuscular junction, likely renders the neuromuscular junction especially vulnerable to age-related mitochondrial dysfunction. Manifestations of mitochondrial dysfunction with aging include impaired respiratory function, elevated reactive oxygen species production, and increased susceptibility to permeability transition, contributing to reduced ATP generating capacity, oxidative damage, and apoptotic signaling, respectively. Using this framework, in this review we summarize our current knowledge, and relevant gaps, concerning the potential impact of mitochondrial impairment on the aging neuromuscular junction, and the mechanisms involved.
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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 | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".