<p>The invention relates to enzymatic assays for assessing protein deacetylase activity of a protein deacetylase family, such as the histone deacetylase (HDAC) family or a sirtuin family. More particularly, the invention relates to such assays utilizing primary intact whole cells taken directly from the body of a mammal. Total protein deacetylase activity or isotype-specific activity is measured using assays which include a cell-permeable substrate that allows the production of a detectable reporter molecule in response to deacetylase activity. The effect of inhibitors and activators of the protein deacetylase family on protein deacetylase activity can also be measured.</p>