title: The role of replicative senescence in cancer and human ageing: utility (or otherwise) of murine models.
abstract: Replicative senescence has the potential both to act as an anti-tumour mechanism, and to contribute to age-related changes in tissue function. Studies on human cells have revealed much, both about the nature of cell division counters, some of which utilize the gradual erosion of chromosomal telomeres, and the downstream signalling pathways that initiate and maintain growth arrest in senescence. A powerful test of the hypothesis that senescence is linked to either ageing or tumour prevention now requires a suitable animal model system. Here we overview the current understanding of replicative senescence in human cells, and address to what extent the senescence of murine cells in culture mirrors this phenomenon. We also discuss whether examples of telomere-independent senescence, such as those seen in mouse embryonic fibroblasts (MEFs) and several human cells types, should be viewed not as a consequence of "inadequate growth conditions", but rather as a powerful potential model system to dissect the selective pressures that occur in the early stages of tumour development, ones that we speculate lead to the observed high frequency of abrogation of p16INK4a function in human cancer.
authors.affiliation: Department of Pathology, University of Wales College of Medicine, Cardiff, UK.
authors.forename: S K
authors.initials: SK
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Kipling
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D023421:Models, Animal; D009369:Neoplasms / Q000209:etiology*; D016615:Telomere; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53