Several lines of evidence suggest that the limited replication potenti
al of normal human cells is due to the presence of an intrinsic geneti
c programme. This ''senescence programme'' is believed to reduce the i
ncidence of cancer by limiting the growth of most of the transformed c
ells arising in vivo, although some cells do escape senescence becomin
g both immortalized and transformed. Here we review the literature tha
t describes the senescence process in terms of gene expression and the
regulation of gene expression by a variety of mechanisms affecting tr
anscription factor activity. We focus on regulation of the c-fos gene
through posttranslational modification of the serum response factor (S
RF) as an example of altered gene expression during cellular aging.