Growth factor responsiveness of cultured human fibroblasts declines with age

A sensitive culture system was used to investigate whether in vitro senescence is associated with loss of responsiveness to relevant growth factors in the cellular environment. Early passage dermal fibroblasts obtained from healthy newborns and adults were maintained 4 to 6 days in medium containing either fetal calf serum or five defined growth factors. Newborn fibroblasts consistently grew far better than adult fibroblasts in both media; dose-response curves demonstrated a greater response by newborn fibroblasts to both serum mitogens and to thrombin, insulin, and epidermal growth factor alone and in combination. These data suggest that newborn fibroblasts generally have greater mitogenic responsiveness than adult fibroblasts and that age-associated loss of growth factor responsiveness may indeed contribute to the decreased proliferative capacity of old cells.