Contact Inhibition of Pleiotropin Pinocytosis as a Critical Factor in Metazoan Cell Ageing

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Abstract
For the biosynthesis of macromolecules in amounts sufficient for indefinite growth or survival in dividing as well as in nondividing metazoan cells, a specific serum protein is required. As the addition of this factor to the medium triggers off a chain of events which leads to RNA, DNA, and protein synthesis, we have called it the pleiotropin. Pleiotropin is taken into the cells by pinocytosis. Pinocytic uptake of pleiotropin is strongly inhibited by a mutual cell-to-cell contact; diploid cells in the stage of contact inhibition of pleiotropin pinocytosis are nutritionally limited, and some changes in life processes may be expected. In continuous culture and in tissues in vivo, these changes may accumulate and ultimately result in an irreversible damage of cells so that old cells are characterized by a low pinocytic activity and by a reduced formation of macromolecules. As pleiotropin increases the saturation density and prolongs the life span of diploid cells in vitro, it is suggested that the loss of division potential in metazoan cells is not a programmed event at the cellular level and that the ageing of static cell populations may be caused by the same nutritional deficiency as that of proliferating cells.

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