The effect of the histone deacetylase inhibitor, trichostatin A, on total histone synthesis, H1(0) synthesis and histone H4 acetylation in peripheral blood lymphocytes increases as a function of increasing age: a model study.

A pilot study was initiated in order to ascertain whether the age of the donor might affect either the induction of the expression of H1(0) or histone H4 acetylation by the very specific histone deacetylase inhibitor, trichostatin A. This was investigated in a cell system which normally does not express this linker histone variant, i.e. peripheral blood lymphocytes (PBL), which were obtained from donors of different ages (25-95 years). Forty-eight hours after activation by the mitogen phytohemaglutinin (PHA), 250 ng of trichostatin A per 10(6) cells per ml culture medium was added and cultured for an additional 24h. Assays were performed 72 h after initiation of cultures, i.e. during the S phase. It was found that in PBL, trichostatin A induced the expression of the linker histone variant, H1(0) as well as histone H4 acetylation, and, more importantly, that these effects were enhanced with increasing age of the donor. More specifically, under the influence of trichostatin A, PBL showed increasing H1(0) synthesis rates and increasing levels of histone H4 acetylation as a function of increasing age of the donor. Moreover, although trichostatin A induced an increasing expression of H1(0) with increasing age, it also concomitantly partially inhibited S phase total histone synthesis. This inhibition also increased as a function of increasing age of the donor.