Age-related changes in the distribution pattern of glycosaminoglycans synthesized by cultured human diploid fibroblasts (WI-38).

A gradual decline in the synthesis of glycosaminoglycans, as evidenced by reduced rates of incorporation of [35S] sulfate and [14C] glucosamine into cellular and medium glycosaminoglycans, was observed during the last (about 5) population doublings before phase-out. The decline was accompanied by a change in the distribution pattern of individual glycosaminoglycans with a relative decrease in the incorporation rate of [14C] glucosamine into cellular and medium hyaluronic acid. The incorporation rate of [14D] glucosamine and [35S] sulfate into cellular and medium heparan sulfate continually increased during the last population doublings ("senescence"). The possibility of a coupling between cell growth and hyaluronic acid synthesis or an involvement of hyaluronic acid in the adhesion of cells (among one another or/and to the substratum), and the functional significance of heparan sulfate as a growth inhibitor were discussed.