Résumé
Human diploid fibroblasts have a finite proliferative lifespan at the end of which they are unable to enter S phase in response to mnitogenic stimulation even though they remain alive for many months.1 The G1 arrest state of senescent cells has much in common with the G l arrest state of early passage quiescent cells, because serum stimulation induces the expression of many early to mid-G1 genes in both senescent and quiescent cells. For example, mitogen-stimulated senescent cells are similar to mitogen-stimulated quiescent cells in their expression of c-myc, c-jun and c-H-ras.2,3,4 Nevertheless, mitogen-stimulated senescent cells are unable to enter S phase, whereas mitogen-stiinulated early passage quiescent cells enter S phase approximately 12–18 hours after stimulation. As a means of investigating the molecular basis for the failure to enter S phase in senescent human fibroblasts, we have sought to identify molecules and/or functions that are deficient in the mitogen response pathways in senescent cells. Since the control of cell proliferation in eukaryotes from yeast to man involves the regulated synthesis, activation and degradation of a family of cyclins, which interact with the Cdc2/CDC28 family of cyclin-dependent kinases (Cdk’s), 5,6 we have been analysing the amount and the activity of several cyclins and Cdk’s in senescent and quiescent human fibroblasts.7,8