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Age-dependent response of lymphocytes in the induction of the linker histone variant, H1 degrees and histone H4 acetylation after treatment with the histone deacetylase inhibitor, trichostatin A.

Abstract：

:In the present study we investigated the age-related response of Phytohemaglutinin (PHA)-activated S phase human lymphocytes isolated from peripheral blood from donors of four different age groups, namely young (25-30 years), mid-aged (40-45 years), senior (60-65 years) and elderly (80-95 years) on the induction of the linker histone variant, H1 degrees and histone H4 acetylation after treatment with the very specific histone deacetylase (HDAC) inhibitor, trichostatin A (TSA). The cell system of peripheral blood lymphocytes is ideal for the study of H1 degrees induction since they do not synthesize this particular linker histone variant. Lymphocytes isolated from peripheral blood were activated with PHA (5 microg/10(6) cells/ml medium) and placed in culture for a duration of 72 h at which time cells are in the S phase. Forty-eight hours after inoculation, TSA (250 ng/10(6) cells/ml medium) was added to the cell cultures for a period of 24 h. Assays were performed 72 h after initiation of cultures. The results showed that the induction of H1 degrees after TSA treatment increased to a statistically significant degree in the elderly age group with respect to both the young and the mid-aged age groups. Moreover histone H4 acetylation was found to increase as a function of increasing donor age. A hyperacetylation pattern was observed even in the youngest age group analyzed. Specifically, the tetra-acetylated (H4.4) H4 form increased to a statistically significant degree with the concomitant decrease in the non-acetylated H4 for (H4.0) as a function of donor age. The other acetylated H4 forms (H4.1, H4.2, and H4.3) remained more or less constant, irrespective of donor age. These results show that the sensitivity of lymphocytes to TSA is enhanced with increasing donor age. Since to date, 11 class I and II HDACs have been isolated that have been found by other investigators to have differential responses to HDAC inhibitors, these findings may indicate that there is also a differential age-related response of certain HDACs or perhaps a senescent-specific HDAC. This line of research warrants further study.

journal_name

Exp Gerontol

journal_title

Experimental gerontology

authors

Kypreou KP,Sourlingas TG,Sekeri-Pataryas KE

doi

10.1016/j.exger.2003.12.014

keywords:

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

469-79

issue

eissn

0531-5565

issn

1873-6815

pii

S0531556504000452

journal_volume

pub_type

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Age-dependent response of lymphocytes in the induction of the linker histone variant, H1 degrees and histone H4 acetylation after treatment with the histone deacetylase inhibitor, trichostatin A.