HISTONE H1 DEPLETION WITH HUMAN CELLULAR AGING: BIOCHEMICAL AND CYTOCHEMICAL EVIDENCES

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Biochemical and immunocytochemical examinations of histone H1 in G1 arrested and senescent human fibroblasts were performed to pursuit the mechanisms of human cell aging in vitro. Examinations of histone synthesis in serum depleted or contact inhibited cell cultures indicated that the ratio of histone synthesis over DNA synthesis and molar synthesis of histone H1 to nucleosomal histones did not decline with accumulation of resting cell populations, while senescent cells had a lower ratio of histone H1 synthesis than young cells. Histone H1 contents plotted as a function of DNA synthesis activity revealed that senescent cultures had a lower content of histone H1 than young cultures at any stage of cell proliferation.
Immunocytological study using antiserum against histone H1 on cocultivated young and senescent cells showed that immunofluorescence intensity was very low in senescent nuclei in comparison with young cell nuclei. Thus, we conclude that a decline in content and synthesis of histone H1 relative to nucleosomal histones with passage number was not simply due to the passage-related accumulation of resting cells, but actually reflects age-specific changes in cycling cells or whole cell populations in the senescent cultures. The depletion of histone H1 in chromatin was discussed as a possible cause of DNA strand break and relaxation of gene repression.