AGING AFFECTS EPIDERMAL GROWTH-FACTOR RECEPTOR PHOSPHORYLATION AND TRAFFIC KINETICS

With increasing donor age, cultured human fibroblasts express fewer ep idermal growth factor receptors and display decreased mitogenic respon siveness to epidermal growth factor. To determine age-associated diffe rences in epidermal growth factor receptor phosphorylation and traffic kinetics, we studied in fibroblasts derived from donors of different ages autophosphorylation of the receptor after ligand binding and traf ficking of the receptor-ligand complexes. We now report an age-associa ted delay in the rate of receptor phosphorylation after epidermal grow th factor stimulation, Furthermore, receptor/ligand trafficking is aff ected by aging. There is an age-associated decrease and delay in the n umber of occupied receptors that are transported intracellularly and i n their rate of clearance from the plasma membrane, Our data show that aging affects receptor/ligand activation and processing and suggest t hat the decreased cellular mitogenic response with aging may be, at le ast in part, the result of decrements in receptor activation and proce ssing. (C) 1996 Academic Press, Inc.