Activation of pericentromeric and telomeric heterochromatin in cultured lymphocytes from old individuals.

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 heterochromatinized 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.