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

Abstract

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.

The Functioning of “Aged” Heterochromatin

“…We have demonstrated also that Co 2+ ions alone and in combination with the bioregulator Livagen can reverse the deheterochromatinization of precentromeric and telomeric heterochromatin ( Fig.9), to normalize the telomere length in cells from old individuals (Lezhava and Jokhadze, 2007;Lezhava et al,2008). Blood cholesterol levels in an animal model (rabbit) for atherosclerosis was reduced (41% on the average) by pretreatment with combination of livagen and CoCl 2 -normalization of telomere length (unpublished data of research -STCU 4307-grants in 2007-2009) (Lezhava et al, 2007(Lezhava et al, -2009. Fig.…”

“…In old age, CoCl 2 alone and in combination with the tetrapeptide bioregulator Livagen enhanced the distribution of SCE; that is, pericentromeric heterochromatin appeared to be more sensitive to the CoCl 2 effect alone (15.4  1.8% SCE), whereas SCE was mostly observed in telomere heterochromatin when CoCl 2 in combination with livagen was used (12  1.2% SCE) (control, 2.8  0.5% SCE, respectively).Because exchanges occur in euchromatic uncondensated regions, the obvious effect of CoCl 2 alone and in combination with Livagen could be attributed to its decondensing deheterochromatinization effect on pericentromeric and telomeric heterochromatin, which would elevate the possibility of SCE ((lezhava and Jokhadze, 2007). At the same time, the deheterochromatinization of telomeric heterochromatin contributes to activation of DNA repair.…”

Gerontology research in Georgia

“…We have demonstrated also that Co 2+ ions alone and in combination with the bioregulator Livagen can reverse the deheterochromatinization of precentromeric and telomeric heterochromatin to normalize the telomere length in cells from old individuals (Lezhava and Jokhadze 2007; Lezhava et al 2008). …”

Health Hazards Among Fire Fighters

“…The difference between our results and Greenstock's findings may be related to the fact that the exposed workers in our research were aged from 18-33 years, 7 workers were 25 years old or above and 17 workers were below 25 years old, and the number examined was small. Lezhava and Jokhadze (2007) studied the functional characteristics of chromosomes (level of total heterochromatin, chromosome insta- Table (7…”