PARACRINE STIMULATION OF SENESCENT SATELLITE CELL-PROLIFERATION BY FACTORS RELEASED BY MUSCLE OR MYOTUBES FROM YOUNG MICE

The proliferative potential of satellite cells undergoes a dramatic de crease in the early postnatal period and a more modest but continuous decrease throughout the life span of the animal. To address the proble m of the mechanism regulating this phenomenon and to understand whethe r it is causally linked to senile muscle atrophy, we studied the respo nse of aged satellite cells to serum and to different growth factors. The data reported indicate a generalised reduction in the response to all mitogens tested, which could not be compensated for by increased c oncentrations of serum or growth factors. On the other hand, condition ed medium of differentiated myotubes from young mice exhibited a stron g mitogenic action on aged satellite cells, while conditioned media of myotubes from old mice or from a variety of non-muscle cells were ine ffective. Furthermore, saline extracts from muscle of young mice are a lso able to exert this mitogenic action. Saline extracts of muscle fro m old mice were poorly mitogenic for satellite cells from young mice, and not at all for satellite cells from old mice. These data indicate that paracrine interactions operate inside the muscle tissue and are p robably required for the normal replicative behaviour of satellite cel ls. The failure of such interactions may be among the causes leading t o age-related muscle hypotrophy.