Age‐related dysfunction in the satellite cell niche
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abstract
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 COL4α1 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.
