Denervation Contributes To Fiber Atrophy And Myosin Heavy Chain Co-expression In Senescent Skeletal Muscle
Bibliographic record
Abstract
Aging is accompanied by a decline in skeletal muscle mass and function, termed sarcopenia, which plays a role in age-related disability. Sarcopenic muscle demonstrates increased muscle fiber size heterogeneity characterized by a marked accumulation of small fibers (fibers < 1000 μm2). One candidate for the accumulation of small fibers is an increase of denervated fibers within the muscle due to failure of re-innervation with aging. PURPOSE: The current study was undertaken to determine the characteristics of both denervated and innervated fibers within red gastrocnemius (GASr) muscle of the Fisher 344 × Brown Norway aging rat model. Rats were studied at 8 and 35 months of age, corresponding to young adulthood (YA) and senescence (SEN) time points. METHODS: Serial cryosections (10 μm) of the GAS were stained by immunofluorescence using antibodies for Nav1.5 (a sodium channel expressed during denervation) as well as either slow or fast myosin heavy chain. Serial images of muscle fibers within the GASr were collected and the fiber cross-sectional area (CSA) as well as fiber type (type I, type IIa, co-expressing) of each fiber was determined. For denervation status, fibers were classified as normal (no Nav1.5), ringed (circumferential expression of Nav1.5), or cytoplasmic Nav1.5 staining. Statistical comparisons used student's T-tests or two-way ANOVAs using a Holm-Sidak post-hoc test, where appropriate. RESULTS: Comparison of GAS wet weight confirmed the presence of sarcopenia (1963±35 mg vs 1294±26 mg, P<0.001). The average CSA of type IIa fibers was significantly smaller in SEN (1869±153 μm2) than YA (2464±156 μm2; P=0.021), while type I fibers demonstrated protection with aging. Fibers expressing both fast and slow myosin heavy chain (co-expressing fibers) were absent in the YA animals, but prevalent within the SEN muscles. Within the SEN group, type I fibers (2497±173 μm2) were significantly larger than both type IIa (1613±158 μm2; P<0.001) and co-expressing fibers (1413±146 μm2; P<0.001). Fibers with ringed staining (1884±151 μm2) were significantly smaller than normal fibers (2334±146 μm2; P=0.039), while fibers with cytoplasmic staining (1305±179 μm2) were smaller than both normal fibers (P<0.001) and fibers with ringed staining (P=0.018). The average CSA for normal fibers was not different between the YA and SEN groups. CONCLUSION: Our results suggest that denervation contributes to fiber atrophy and myosin heavy chain co-expression in aged muscles. These results implicate denervation as a key player in sarcopenia, particularly at advanced stages where muscle atrophy becomes severe. Funded by CIHR and AHFMR
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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".