ABSTRACT
In this chapter, the author describes experiments that have allowed us to distinguish between these two categories of mechanisms responsible for cellular aging and which support the idea that a genetic program is involved. Treatment of quiescent and senescent fibroblast monolayers (human foreskin fibroblasts, CSC303) with the detergent octyl-3-D-glucopyranoside results in solubilization of these inhibitor proteins. The selection system used for isolating the hybrids was one that had been used by many other investigators, one which involved the generation of double-mutant parent cell lines that had both a recessive and a dominant mutation. If one accepts the hypothesis that the inhibitor of DNA synthesis that is expressed in senescent cells is the end point of a genetic program that is responsible for the aging process, a number of mechanisms can be postulated for escape from senescence. The authors provide strong evidence that cellular senescence is an active process resulting from the genetic program of normal cells.
