Growth factors as probes of cell aging

We present examples of four types of alterations which contribute to the senescence phenotype of WI-38 cells: a) in senescent cells there is an increased lability of the tyrosine autophosphorylation capacity of detergent isolated EGF receptor; b) following serum stimulation, the calmodulin protein level fails to increase in senescent cells, although the calmodulin mRNA level increases as expected; c) following heat shock at 43 degrees C, senescent cells produce both less RNA and less protein for the HSP70 and HSP90 genes; d) we find that membranes isolated in basic buffer from senescent or young cells increase the EGF proliferative response of senescing cells, in contrast to the finding by others that membranes isolated in neutral buffer inhibit cell proliferation (Pereira-Smith et al., Senescent and quiescent cell inhibitors of DNA synthesis Exp. Cell Res. 160, 297-306, 1985; Stein and Atkins, Membrane-associated inhibition of DNA synthesis in senescent human diploid fibroblasts: Characterization and comparison to quiescent cell inhibitor. Proc. Natl. Acad. Sci. USA 83 9030-9034, 1986). We conclude that senescence alterations are complex and occur at many levels, and that senescence changes are not identical to quiescence features.