Regulation of transcription factor activity during cellular aging

Several lines of evidence suggest that the limited replication potential of normal human cells is due to the presence of an intrinsic genetic programme. This ''senescence programme'' is believed to reduce the incidence of cancer by limiting the growth of most of the transformed cells arising in vivo, although some cells do escape senescence becoming both immortalized and transformed. Here we review the literature that describes the senescence process in terms of gene expression and the regulation of gene expression by a variety of mechanisms affecting transcription factor activity. We focus on regulation of the c-fos gene through posttranslational modification of the serum response factor (SRF) as an example of altered gene expression during cellular aging.