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 spon taneous tumor development in genetically modified mice. Analysis of various transgenic and knockout rodent models with either a shortened or an extend ed life span, provides a unique opportunity to evaluate interactions of gen es involved in the aging process and carcinogenesis. There are only a few m odels which show life span extension. Ames dwarf mutant mice, p66(-/-) knoc kout mice, alpha MUPA and MGMT transgenic mice live longer than wild-type s trains. The incidence of spontaneous tumors in these mutant mice was usuall y similar to those in controls, whereas the latent period of tumor developm ent was increased. Practically all models of accelerated aging showed incre ased incidence and shorter latency of tumors. This phenomenon has been obse rved in animals which display a phenotype that more closely resembles natur al aging, and in animals which manifest only some features of the normal ag ing process. These observations are in agreement with an earlier establishe d positive correlation between tumor incidence and the rate of tumor incide nce increase associated with aging and the aging rate in a population. Thus , genetically modified animals are a valuable tool in unravelling mechanism s underlying aging and cancer. Systemic evaluation of newly generated model s should include onco-gerontological studies. (C) 2001 Elsevier Science Ire land Ltd. All rights reserved.