Aging of human fibroblasts in vitro: surface features and behavior of aging WI 38 cells

WI 38 cells at various in vitro ages and an SV 40 virus tranformed variant were examined by (3)H thymidine autoradiography, time lapse cinematography and scanning electron microscopy. Among normal WI 38 cells it was shown that htere was a good correlation between cellular morphology, behavior, and the ability to incorporate (3)H thymidine. Small, elongate spindle-shaped cells were usually both active incorporators of (3)H thymidine, as determined autoradiographically, and dividers as determined by time lapse cinematography; larger, more spread out cells tended to be nondividers. The proportion of large, nondividing cells increased with increasing in vitro age and was correlated with changes in cell surface and behavior. Transformed WI 38 cells exhibited no such changes as a function of age. Results support the thesis that in vitro aging reflects the inability of individual cells to undertake DNA synthesis and to complete division, but nondividers continue to enlarge and unusual sizes and shapes are attained. Associated with these aging changes were conspicuous alterations in cellular curface features and behavior.