Aging Affects Epidermal Growth Factor Receptor Phosphorylation and Traffic Kinetics

With increasing donor age, cultured human fibroblasts express fewer epidermal growth factor receptors and display decreased mitogenic responsiveness to epidermal growth factor. To determine age-associated differences 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 trafficking of the receptor-ligand complexes. We now report an age-associated delay in the rate of receptor phosphorylation after epidermal growth factor stimulation. Furthermore, receptor/ligand trafficking is affected by aging. There is an age-associated decrease and delay in the number of occupied receptors that are transported intracellularly and in their rate of clearance from the plasma membrane. Our data show that aging affects receptor/ligand activation and processing and suggest that the decreased cellular mitogenic response with aging may be, at least in part, the result of decrements in receptor activation and processing.