Niche for the aged
Targeting integrin β1 or fibronectin for muscle repair in the aged
A pair of Nature Medicine studies has placed integrin β1 signaling at the center of post-injury muscle regeneration in elderly patients. With one study pointing to the receptor and the other to its ligand, the results provide two new targets for drug discovery, and shed light on how dysfunctional interactions between muscle stem cells and their surrounding environment underlie the loss of muscle healing with age.
Integrins are cell surface receptors that bind ligands in the extracellular matrix to support adhesion and relay information about the environment into the cell. The most abundant integrin receptor subunit, integrin β1, is known to bind fibronectin, an extracellular protein important for muscle stem cell renewal.
While muscle stem cells - also known as satellite cells - play a key role in recovery from injury, it's not clear what part of the process goes wrong during aging when the ability of skeletal muscle to repair itself declines.
In healthy tissue, satellite cells stay quiescent in their specialized niches - extracellular matrix-filled pockets between the basal lamina and mature muscle fibers. After injury, changes in the niche prompt the stem cells to proliferate and differentiate, replacing