Age-related decline in the synthesis of glycosaminoglycans by cultured human 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 total cellular and extracellular glycosaminoglycans, occurred during the last 4 to 5 passages (1 : 2 splits) of WI-38 cultures before phase out. While labelling of cellular glycosaminoglycans by both radioactive precursors was reduced to about the same extent, a relatively greater decline in [35S]-sulfate than in [14C]-glucosamine incorporation into extracellular glycosaminoglycans was observed during the last passages. These changes in glycosaminoglycan metabolism are interpreted as an expression of cellular aging and a function of glycosaminoglycans in growth regulation (and possibly in the process of cellular senescence) is discussed.