Somatomedin C-binding and action in fibroblasts from aged and progeric subjects

Aging is associated with diminished cell growth, which has been ascribed in part to decreased cellular responsiveness to serum mitogens. To investigate whether there is an age-related loss of responsiveness to somatomedin-C (SM-C), we studied SM-C binding and action in early passage fibroblasts from normal donors, aged 7-96 yr, and one progeric subject. SM-C stimulated [3H]thymidine incorporation 4- to 16-fold in young cells, 4- to 17-fold in aged cells, and 4- to 11-fold in progeric cells. SM-C was synergistic with 0.25% human hypopituitary serum in stimulating [3H]thymidine incorporation in all cell lines. Dose-response curves for SM-C stimulation of thymidine incorporation were not significantly altered in aged or progeric cells. Half-maximal responses occurred at 5-15 ng/ml SM-C for all cell lines. [3H]Thymidine incorporation results were supported by cell replication studies. In addition, binding of [125I] SM-C was virtually identical in all cell lines, with 50% displacement at 2-5 ng/ml SM-C. Thus, in vivo aging does not appear to be associated with either an alteration in SM-C receptors or a diminished cellular responsiveness to SM-C's mitogenic effects.