Introduction

One of the fundamental properties of mitotically competent human somatic cells is an innately programmed barrier to unlimited proliferation. This process, known as replicative (or proliferative) senescence, may serve as one of many safeguards to maintain cellular integrity necessitated by the extended longevity of humans. Species such as rodents, which live for only a few years, can protect cells by such functions as DNA repair and antioxidant pathways. In humans, these conventional cellular defense strategies, which might otherwise fail over the many decades of human life, are bolstered by the mechanism of replicative senescence.

It is believed that a restriction in the number of cell divisions may serve as a protection against the potential for multiple mutations that are required for the development of a cancer cell from a cell that is normal. The replicative senescence program is a strict characteristic of human, as opposed to mouse, cells, and in fact there is no documented case of a normal human cell undergoing spontaneous immortalization in cell culture. By contrast, mouse cells transform quite frequently in cell culture, becoming immortal cell lines. Parallel observations have been made in vivo: mice show high rates of cancer within their three-year lifespan, whereas most human cancers occur after age 50.