| Title |
Failed reinnervation in aging skeletal muscle
|
|---|---|
| Published in |
Skeletal Muscle, September 2016
|
| DOI | 10.1186/s13395-016-0101-y |
| Pubmed ID | |
| Authors |
Sudhakar Aare, Sally Spendiff, Madhusudanarao Vuda, Daren Elkrief, Anna Perez, Qinghua Wu, Dominique Mayaki, Sabah N. A. Hussain, Stefan Hettwer, Russell T. Hepple |
| Abstract |
Skeletal muscle displays a marked accumulation of denervated myofibers at advanced age, which coincides with an acceleration of muscle atrophy. In 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). Both 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. Our 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. |
X Demographics
The data shown below were collected from the profiles of 22 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 6 | 27% |
| United Kingdom | 4 | 18% |
| Australia | 3 | 14% |
| Brazil | 1 | 5% |
| Taiwan | 1 | 5% |
| Norway | 1 | 5% |
| Unknown | 6 | 27% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 11 | 50% |
| Scientists | 8 | 36% |
| Practitioners (doctors, other healthcare professionals) | 2 | 9% |
| Science communicators (journalists, bloggers, editors) | 1 | 5% |
Mendeley readers
The data shown below were compiled from readership statistics for 115 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 115 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 17 | 15% |
| Student > Ph. D. Student | 16 | 14% |
| Student > Master | 14 | 12% |
| Student > Bachelor | 11 | 10% |
| Student > Doctoral Student | 8 | 7% |
| Other | 16 | 14% |
| Unknown | 33 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 17 | 15% |
| Medicine and Dentistry | 17 | 15% |
| Agricultural and Biological Sciences | 12 | 10% |
| Sports and Recreations | 9 | 8% |
| Neuroscience | 8 | 7% |
| Other | 12 | 10% |
| Unknown | 40 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 12. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 January 2018.
All research outputs
#2,468,081
of 23,577,654 outputs
Outputs from Skeletal Muscle
#55
of 368 outputs
Outputs of similar age
#43,967
of 339,606 outputs
Outputs of similar age from Skeletal Muscle
#2
of 10 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 368 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.3. This one has done well, scoring higher than 85% of its peers.
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