In comparison to healthy cells, cancerous cells exhibit decreased monoacetylated and trimethylated forms of histone H4 (decreased H4ac and H4me3).[21] Additionally, mouse models have shown that a decrease in histone H4R3 asymmetric dimethylation (H4R3me2a) of the p19ARF promoter is correlated with more advanced cases of tumorigenesis and metastasis.[22] In mouse models, the loss of histone H4 acetylation and trimethylation increases as tumor growth continues.[21] Loss of histone H4 Lysine 16 acetylation (H4K16ac), which is a mark of aging at the telomeres, specifically loses its acetylation. Some scientists hope this particular loss of histone acetylation might be battled with a histone deacetylase (HDAC) inhibitor specific for SIRT1, an HDAC specific for H4K16.[9][23]