We have investigated the role of the IGF-1 receptor in the proliferation of young and senescent human diploid fibroblasts. Using WI-38 cells, we have established the following: 1) both young and senescent cells have IGF-1 receptors, which can be autophosphorylated by IGF-1, the intensity of the autophosphorylation being roughly the same in both types of cells; 2) the levels of IGF-1 receptor mRNA are also similar in young and senescent cells; 3) both young and senescent cells have an absolute requirement for the IGF-1 receptor in order to be stimulated by either serum or SV40, respectively; 4) despite these similarities, young cells respond to IGF-1 (in combination with other growth factors) with DNA synthesis and mitosis, and senescent cells do not. We conclude that, although the IGF-1 receptor is still needed by senescent cells for a growth response to SV40, it is not, by itself, the determinant of senescence, at least in WI-38 cells.
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