PROLIFERATIVE HOMEOSTASIS AND ITS AGE-RELATED ABERRATIONS

Although it is possible that, in some aging tissues, altered proliferative homeostasis serves a beneficial function, it seems more likely that the effects are usually detrimental to the organism, not because there are deficiencies of certain cell types but, on the contrary, because there seem to be numerous examples, in mammals, of multi-focal proliferations or hyperplasias, often occurring in tissues in which there is evidence of atrophy, or of a decline in the replicative potentials of certain cell types, some of which might serve to regulate the proliferative homeostasis of related cell types. Perhaps the most important consequence of such age-related hyperplasias is that they could set the stage for tumor promotion - the second stage of the classical two stage mechanism of chemical carcinogenesis. Such a pathogenetic paradigm has also been implicated in atherogenesis. Thus, we are concerned with mechanisms which may be at the basis of the two major disease categories of modern man - cancer and atherosclerosis. A rigorous experimental approach to the altered proliferative homeostasis which underlies these disorders requires the molecular characterization and biological assay of those numerous chemical agents which either stimulate cell replication (mitogens") or inhibit cell replication ("chalones") in specific cell types. The symposium which this paper introduces reviews the present state of knowledge of several examples of each of these two important classes of cell cycle regulators. © 1979."