A crucial test for the proposed roles of cellular senescence and apoptosis in aging and age-related disease is to manipulate these processes in intact organisms. At present, this approach is practical only in mice. Mice are now fairly easy to manipulate genetically, and their small size and relatively short life span make them the mammalian model of choice for aging studies. There is, however, always the caveat that mice are not humans, and there are significant differences between mouse and human cells in processes that are likely important in aging (e.g., telomere biology and oxidative stress resistance) (8,16). With that caveat in mind, what do mouse models tell us about the roles of cellular senescence and cell death in aging? There are numerous mouse models of accelerated or retarded aging, and it is beyond the scope of this chapter to review them all. Therefore the discussion below focuses on a sampling of informative models, particularly those that elucidate the relationship between cell fate and organismal aging and life span. Two broad categories of mouse models for studying aging are discussed here: those that accelerate aging and those that retard aging.
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