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Age‐related dysfunction in the satellite cell niche

2018· article· en· W3173599718 on OpenAlexaff
Aaron Thomas, Joshua P. Nederveen, Tim Snijders, Sophie Joanisse, Kirsten E. Bell, Stuart M. Phillips, Dinesh Kumbhare, Gianni Parise

Bibliographic record

VenueThe FASEB Journal · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMuscle Physiology and Disorders
Canadian institutionsUniversity of TorontoMcMaster University
Fundersnot available
KeywordsSkeletal muscleNicheTrichromeInternal medicineMasson's trichrome stainEndocrinologyChemistryBiologyAnatomyMedicineImmunohistochemistryH&E stainBiochemistry

Abstract

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Skeletal muscle satellite cells (SC) are important for maintenance and repair of myofibers. SC function and responsiveness is regulated, at least in part, through interactions with niche components in which they reside. Recent evidence suggests that structural changes occur in the SC niche as a function of aging. In the present study, we aimed to investigate whether age has an impact on the properties of the SC niche. Muscle biopsies were obtained from the vastus lateralis of previously untrained but otherwise healthy young men (YM: 21±0.4 yrs; n=10) and old men (OM: 66±0.9 yrs; n=11) at rest. In addition, OM (n =10) performed a single bout of resistance exercise and additional muscle biopsies were taken 24 h and 48 h post‐exercise. Skeletal muscle SC niche measurements were assessed using high resolution immunofluorescent and confocal microscopy. We report changes in the muscle SC niche with aging and that many of these differences are primarily associated with type II fibres. Type II SC niche laminin thickness was significantly greater in OM (1.86 ± 0.06 μm) as compared to YM (1.55 ± 0.09 μm, p<0.05). Mean intensity of collagen IV was significantly lower in OM (92 ± 10 a.u) as compared to YM (512 ± 17 a.u, p<0.05). In OM, the fibrotic index as measured by Masson's trichrome staining was greater (3.6 ± 0.5 %) at baseline, as compared to YM (2.0 ± 0.5 %; p<0.05). We also observed the presence of SC fully incarcerated by the basal lamina. At baseline, 100% of OM possessed SC that were incarcerated, as compared to ~40% of YM. The percentage of SC in mixed muscle that were incarcerated by laminin was greater in OM (19.0 ± 1.6%) as compared to YM (7.2 ± 2.1; p<0.05). Although this phenomenon was present in both Type I and Type II fibres, it appeared exaggerated in Type I fibres (OM: 28.4 ± 8.2%, YM: 3.6 ± 2.1%; p<0.05). In all cases the greatest proportion of active SC were found in the non‐incarcerated population, whereas incarcerated cells were less likely to activate (24 h post exercise – Non‐incarcerated:32 ± 6% active, Incarcerated: 8 ± 2% active, p<0.05). Consistent with this, at 24 h, there was a significantly lower number of quiescent SC in the non‐incarcerated condition (62 ± 7 %) as compared to the incarcerated condition (92 ± 4%, p<0.05). Additional evidence of age‐related dysfunction includes larger myonuclear CSA, increased expression of C OL4 α 1 mRNA and Laminin subunits α2 and β1 was significantly greater in OM as compared to YM. Together this data suggests there are age‐related changes in the niche that are potentially detrimental to SC function and skeletal muscle health. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.010
GPT teacher head0.232
Teacher spread0.222 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2018
Admission routes1
Has abstractyes

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