Cellular senescence: Its role in tumor suppression and aging

Abstract

In normal tissue, cell division is carefully regulated to maintain the correct proliferative balance. Abnormal cell division underlies many hypoproliferative and hyperproliferative disorders, including cancer, and a better understanding of the mechanisms involved could lead to new strategies for treatment and prevention. Cellular senescence, a state of irreversible growth arrest, was first described as a limit to the replicative life span of somatic cells after serial cultivation in.vitro. Recently, however, it has also been shown to be triggered prematurely by potentially oncogenic stimuli such as oncogene expression, oxidative stress, and DNA damage in cell culture studies. These data suggest that cellular senescence is therefore acting as a tumor-protective fail-safe mechanism. However, the significance of cellular senescence has remained an issue of debate over the years, with the possibility that it might be a cell culture-related artifact. Recent reports on oncogene-induced senescence detected in premalignant tumors have provided evidence to validate its role as a physiological response to prevent oncogenesis in vivo. In this review, we discuss the mechanisms for cellular senescence and its roles in vivo. © 2009 Japanese Cancer Association.