Somatomedin C-Binding and Action in Fibroblasts from Aged and Progeric Subjects*

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Abstract
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-relatedloss of responsiveness to somatomediq-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 2-5ng⁄ml SM-C. Thus, in vivo aging does not appear o t be associated with either an alteration in SM-C receptors or a diminished cellular responsiveness to SM-C's mitogenic effects.