Quiescent satellite cells lie beneath muscles, and their self-renewal and differentiation abilities (once they have been activated) ensure muscle repair. These properties, as well as the number of satellite cells, decline with age. Brack and colleagues now show that the muscle fibres that constitute the satellite-cell niche provide signals that induce satellite cells to exit quiescence and lose self-renewal capacity (Nature http://doi.org/jhr; 2012).

Using a pulse-chase of histone-2B–GFP to monitor proliferation of satellite cells in mice, they observe that a subset of aged satellite cells cycle more frequently at homeostatic conditions and express fewer quiescence-associated markers, as well as more differentiation- and apoptosis-associated markers, than surrounding satellite cells. Aged cycling satellite cells injected into muscle were shown to contribute less to myofibres. Interestingly, the authors found that fibroblast growth factor 2 (FGF2) is expressed at higher levels in aged muscle fibres than in younger fibres. Incubation of cultured quiescent adult satellite cells with aged muscle fibre extracts or with FGF2 induced their proliferation; treatment of aged satellite cells with inhibitors of FGF receptors had the converse effect. The authors found that aged satellite cells express an inhibitor of FGF signalling, Sprouty, but its inhibitory effect can be overcome by the high levels of FGF2 produced by the muscle fibres. Finally, using a combination of pharmacological and genetics approaches, they showed that FGF modulation in vivo can indeed influence the regenerative capacity of satellite cells.