AI Article Synopsis
- Scientists found that as muscles get older, they lose a important protein called fibronectin (FN), which helps muscle stem cells stick to their environment and work properly.
- Without enough FN, muscle stem cells can’t stay healthy and can decrease in number, making it harder for muscles to recover from injury.
- If they add FN back to the old muscle environment, the stem cells can work better again and help muscles heal like they did when they were younger.
Article Abstract
Age-related changes in the niche have long been postulated to impair the function of somatic stem cells. Here we demonstrate that the aged stem cell niche in skeletal muscle contains substantially reduced levels of fibronectin (FN), leading to detrimental consequences for the function and maintenance of muscle stem cells (MuSCs). Deletion of the gene encoding FN from young regenerating muscles replicates the aging phenotype and leads to a loss of MuSC numbers. By using an extracellular matrix (ECM) library screen and pathway profiling, we characterize FN as a preferred adhesion substrate for MuSCs and demonstrate that integrin-mediated signaling through focal adhesion kinase and the p38 mitogen-activated protein kinase pathway is strongly de-regulated in MuSCs from aged mice because of insufficient attachment to the niche. Reconstitution of FN levels in the aged niche remobilizes stem cells and restores youth-like muscle regeneration. Taken together, we identify the loss of stem cell adhesion to FN in the niche ECM as a previously unknown aging mechanism.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467443 | PMC |
| http://dx.doi.org/10.1038/nm.4126 | DOI Listing |
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