Mutant and genetically modified mice as models for studying the relationship between aging and carcinogenesis

Increased interest is emerging in using mouse models to assess the genetics of aging and age-related diseases, including cancer. However, only limited information is available regarding the relationship between aging and spontaneous tumor development in genetically modified mice. Analysis of various transgenic and knockout rodent models with either a shortened or an extended life span, provides a unique opportunity to evaluate interactions of genes involved in the aging process and carcinogenesis. There are only a few models which show life span extension. Ames dwarf mutant mice, p66(-/-) knockout mice, alpha MUPA and MGMT transgenic mice live longer than wild-type strains. The incidence of spontaneous tumors in these mutant mice was usually similar to those in controls, whereas the latent period of tumor development was increased. Practically all models of accelerated aging showed increased incidence and shorter latency of tumors. This phenomenon has been observed in animals which display a phenotype that more closely resembles natural aging, and in animals which manifest only some features of the normal aging process. These observations are in agreement with an earlier established positive correlation between tumor incidence and the rate of tumor incidence increase associated with aging and the aging rate in a population. Thus, genetically modified animals are a valuable tool in unravelling mechanisms underlying aging and cancer. Systemic evaluation of newly generated models should include onco-gerontological studies. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.