Model: the age-related decline in HDAC levels contributes to replicative senescence. As WI-38 cells enter senescence, cellular HDAC activity is envisioned to decrease to alter gene expression. The reduction in HDAC activity induces the expression of p21WAF1 to assist in senescence-associated growth arrest. It is also envisioned that the decline in HDAC activity contributes to the senescence-associated drop in proteasome activity.
Place et al. BMC Cell Biology 2005 6:37 doi:10.1186/1471-2121-6-37