Activating FGFR1 restores Integrin-β1--mediated fibronectin sensing in satellite cells of aged mice
Abstract
Muscle satellite cells (SCs), essential for skeletal muscle regeneration, decline in number and function with age, contributing to sarcopenia. A fully defined viscoelastic hydrogel that preserves SC-myofiber interactions and supports tunable densities of fibronectin-derived RGD ligands was used to investigate age-related defects in extracellular matrix sensing by SCs. Elevating RGD density increased the number of activating and proliferating SCs on myofibers from young mice, whereas SCs from aged mice were unresponsive. Loss of FGF receptor 1 signaling in SCs from aged mice abrogated the coordinated Syndecan-4 and Integrin-{beta}1 matrix response observed in SCs from young mice. Activating Integrin-{beta}1 promoted asymmetric division and self-renewal in SCs from young mice whereas combined FGFR1 and Integrin-{beta}1 signaling drove symmetric expansion. In SCs from aged mice, FGFR1 dysfunction disrupted this balance, impairing asymmetric division, but constitutive FGFR1 activation restored receptor co-localization, self-renewal, and fibronectin responsiveness. Therefore, FGFR1 integrates matrix and growth factor signals, suggesting that targeting the FGFR1--Integrin-{beta}1 axis may enhance SC regenerative potential in aging organisms.
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Research summary
Activating FGFR1 restores fibronectin sensing and self-renewal in aged satellite cells. The paper addresses the decline in muscle satellite cell function with age, which is a root cause of sarcopenia and aging-related muscle degeneration, thus contributing to the understanding of mechanisms that could enhance regenerative potential in aging organisms.
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