Evidence map›Paper›PMID 27588166›Full record

ArticleSkeletal muscle2016

Failed reinnervation in aging skeletal muscle.

Sudhakar Aare, Sally Spendiff, Madhusudanarao Vuda, Daren Elkrief, Anna Perez, Qinghua Wu, Dominique Mayaki, Sabah N A Hussain, Stefan Hettwer, Russell T Hepple

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Skeletal muscle, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 2 pooled it
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
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  10. The sarcopenia-pain connection: why mechanisms matter for patient care?Frontiers in pain research (Lausanne, Switzerland) · 2026
    Review
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  15. Reactive oxygen species in the pathogenesis of sarcopenia.Free radical biology & medicine · 2025
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. The effects of resistance training on denervated myofibers, senescent cells, and associated protein markers in middle-aged adults.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Sudhakar AareResearch Institute of the McGill University Health Centre, EM2.2232, RI MUHC, 1001 Decarie Blvd, Montreal, QC Canada H4A 3J1 ; McGill Research Centre for Physical Activity and Health, McGill University, Montreal, QC Canada.
Sally SpendiffResearch Institute of the McGill University Health Centre, EM2.2232, RI MUHC, 1001 Decarie Blvd, Montreal, QC Canada H4A 3J1 ; McGill Research Centre for Physical Activity and Health, McGill University, Montreal, QC Canada.
Madhusudanarao VudaResearch Institute of the McGill University Health Centre, EM2.2232, RI MUHC, 1001 Decarie Blvd, Montreal, QC Canada H4A 3J1 ; McGill Research Centre for Physical Activity and Health, McGill University, Montreal, QC Canada.
Daren ElkriefResearch Institute of the McGill University Health Centre, EM2.2232, RI MUHC, 1001 Decarie Blvd, Montreal, QC Canada H4A 3J1 ; McGill Research Centre for Physical Activity and Health, McGill University, Montreal, QC Canada ; Department of Kinesiology and Physical Education, McGill University, Montreal, QC Canada.
Anna PerezResearch Institute of the McGill University Health Centre, EM2.2232, RI MUHC, 1001 Decarie Blvd, Montreal, QC Canada H4A 3J1.
Qinghua WuResearch Institute of the McGill University Health Centre, EM2.2232, RI MUHC, 1001 Decarie Blvd, Montreal, QC Canada H4A 3J1 ; McGill Research Centre for Physical Activity and Health, McGill University, Montreal, QC Canada.
Dominique MayakiResearch Institute of the McGill University Health Centre, EM2.2232, RI MUHC, 1001 Decarie Blvd, Montreal, QC Canada H4A 3J1.
Sabah N A HussainResearch Institute of the McGill University Health Centre, EM2.2232, RI MUHC, 1001 Decarie Blvd, Montreal, QC Canada H4A 3J1.
Stefan HettwerNeurotune, Zurich, Switzerland.
Russell T HeppleResearch Institute of the McGill University Health Centre, EM2.2232, RI MUHC, 1001 Decarie Blvd, Montreal, QC Canada H4A 3J1 ; McGill Research Centre for Physical Activity and Health, McGill University, Montreal, QC Canada ; Department of Kinesiology and Physical Education, McGill University, Montreal, QC Canada.
McGill University Health Centre · CANeurotune (Switzerland) · CH

Funding

CIHR MOP 119583CIHR MOP 125986
6 · The paper itself

Abstract

backgroundSkeletal muscle displays a marked accumulation of denervated myofibers at advanced age, which coincides with an acceleration of muscle atrophy.

methodsIn this study, we evaluated the hypothesis that the accumulation of denervated myofibers in advanced age is due to failed reinnervation by examining muscle from young adult (YA) and very old (VO) rats and from a murine model of sporadic denervation secondary to neurotrypsin over-expression (Sarco mouse).

resultsBoth aging rat muscle and Sarco mouse muscle exhibited marked fiber-type grouping, consistent with repeating cycles of denervation and reinnervation, yet in VO muscle, rapsyn at the endplate increased and was associated with only a 10 % decline in acetylcholine receptor (AChR) intensity, whereas in Sarco mice, there was a decline in rapsyn and a 25 % decrease in AChR intensity. Transcripts of muscle-specific kinase (21-fold), acetylcholine receptor subunits α (68-fold), ε (threefold) and γ (47-fold), neural cell adhesion molecule (66-fold), and runt-related transcription factor 1 (33-fold) were upregulated in VO muscle of the rat, consistent with the marked persistent denervation evidenced by a large proportion of very small fibers (>20 %). In the Sarco mice, there were much smaller increases in denervation transcripts (0-3.5-fold) and accumulation of very small fibers (2-6 %) compared to the VO rat, suggesting a reduced capacity for reinnervation in aging muscle. Despite the marked persistent denervation in the VO rat muscle, transcripts of neurotrophins involved in promoting axonal sprouting following denervation exhibited no increase, and several miRNAs predicted to suppress neurotrophins were elevated in VO rat.

conclusionsOur results support the hypothesis that the accumulation of denervated fibers with aging is due to failed reinnervation and that this may be affected by a limited neurotrophin response that mediates axonal sprouting following denervation.

Indexed as

AnimalsCore Binding Factor Alpha 2 SubunitMaleMiceMice, Inbred C57BLMuscle, SkeletalNerve Growth FactorsPhospholipases A2, CytosolicRatsRats, Inbred F344Receptor Protein-Tyrosine KinasesReceptors, CholinergicSarcopeniaCore Binding Factor Alpha 2 SubunitMuSK protein, mouseNerve Growth FactorsPhospholipases A2, CytosolicReceptor Protein-Tyrosine KinasesReceptors, CholinergicAgingDenervationMicroRNAMuscle atrophyNeurotrophinsReinnervationSarcopeniaSkeletal muscle

Identifiers

PMID27588166
PMCPMC5007704
OpenAlexW2512477469

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.