Activation of Pericentromeric and Telomeric Heterochromatin in Cultured Lymphocytes from Old Individuals

摘要

The functional characteristics of chromosomes (level of total heterochromatin, chromosome instability, and sister chromatid exchanges [SCEs]) were studied in cultured lymphocytes derived from 80- to 91-year-old and 18- to 30-year-old (control group) individuals under the single and combined effect of CoCl_2 and bioregulator Livagen. The results obtained showed that chromosome heterochromatinization (condensation of eu- and heterochromatin regions) had progressively increased with aging and led to inactivation of a number of once functioning "active genes." The peptide bioregulator Livagen could induce reactivation (deheterochromatinization) of chromatin to modify hetero-chromatinized chromosomal regions in cultured lymphocytes of aged individuals. Our results indicated that metal ions (CoCl_2) caused a significant increase in the level of chromosomal aberrations in old donors in comparison with the control group (P < 0.05). The peptide bioregulator Livagen was effective in decreasing the number of changes induced by the CoCl_2 3.4 ± 0.6% (control group 4.2 ± 0.7%). Co~(2+) ions single and Co~(2+) ions in combination with the Livagen changed the distribution of SCE over chromosomes: pericentromeric heterochromatin was more sensitive to the effect of CoCl_2 (15.4 ± 1.8% SCE), while SCE were mostly registered in telomeric heterochromatin under the combined effect of CoCl_2 and Livagen 12.0 ± 1.2% SCE (control group 4.5 ± 0.6% and 2.8 ± 0.5% SCE, respectively). Thus, we have first demonstrated that Co~(2+) ions separately and in combination with the bioregulator Livagen have different chromosomal target regions as demonstrated by SCE induction, deheterochromatinization of precentromeric and telomeric heterochromatin in lymphocytes from old individuals.