Age-dependent modifications of gene expression in human fibroblasts.

Normal human fibroblasts exhibit a limited proliferative potential in culture. When populations are serially subcultured, they grow well initially, but ultimately reach a stage when they are no longer able to proliferate in response to mitogenic stimuli. This state is designated "replicative senescence". In addition to failure to proliferate, numerous morphological and physiological changes characterize the senescent phenotype. Both stochastic and genetic mechanisms have been postulated as causal effectors of the aging process. However, the pathway leading to cellular senescence is likely to be complex with numerous changes. In this article we provide an overview of cell and molecular changes that occur during cell aging, with special emphasis on signal transduction pathways and cell cycle proteins that are likely to play key roles in determining the limited replicative life span and the changes that occur.