Remodeling of heterochromatin induced by heavy metals in extreme old age.

The levels of chromosome instability and heat absorption of chromatin have been studied in cultured lymphocytes derived from blood of 80-93- and 18-30-year-old individuals, under the effect of heavy metal Cu(II) and Cd(II) salts. The analysis of the results obtained indicates that 50 µM Cu(II) induced a significantly higher level of cells with chromosome aberrations in old donors (13.8 ± 1.5% vs control, 3.8 ± 1.7%), whereas treatment with 100 µM Cd(II) did not induce any changes in the background index. Analysis of the lymphocyte melting curves showed that Cu(II) ions caused more effective condensation of heterochromatin in old healthy individuals compared with young donors, which was expressed by the increase of the T (m) of elderly chromatin by ~3°C compared with the norm. Treatment of lymphocyte chromatin of old individuals with 100 µM Cd(II) caused decondensation (deheterochromatinization) of both the facultative and constitutive domains of heterochromatin. The deheterochromatinization T (m) was decreased by ~3-3.5°C compared with the T (m) observed for young individuals. Thus, the chromatin of cultured lymphocytes from the old-aged individuals underwent modification under the influence of copper and cadmium salts. Cu(II) caused additional heterochromatinization of heterochromatin, and Cd(II) caused deheterochromatinization of facultative and constitutive heterochromatin. Our data may be important as new information on the remodeling of constitutive and facultative heterochromatin induced by heavy metals in aging, aging pathology, and pathology linked with metal ions.

Gerontology research in Georgia.

Gerontology research carried out in different scientific centers of Georgia follows the basic directions of most work in this field: epidemiology, investigation of the mechanisms of aging, and finding ways to prevent senile pathologies and to prolong life. The genealogy and epidemiology of long-living peaple have been studied in areas with high occurrence of these people by considering the sex ratio and social status of the long-living, the influence of environmental factors, and the development of senile pathologies. According to the centrosome (centriole) model of aging, the centrosomes and the cytoskeleton, important structures in cellular differentiation and morphogenesis, may be involved in the initiation of the replication senescence mechanism. Our analysis of genetic studies shows that progressive chromosome heterochromatinization (condensation of eu- and heterochromatin regions) occurs in aging. Decreases in the repair processes and increases in the frequency of chromosome aberrations during aging are secondary to this progressive chromosome heterochromatinization. Chromosome heterochromatinization is a key factor in aging but may be reversible under the influence of bioregulators, some chemical substances, and heavy metal salts. The study of chromosome heterochromatinization may provide clues to the potential for prolonging the human lifespan.

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.

Bioregulator Vilon-induced reactivation of chromatin in cultured lymphocytes from old people.

The effect of the synthetic peptide bioregulator Vilon on structural and facultative heterochromatin of cultured lymphocytes from old people has been studied. The data obtained indicate that Vilon (a) induces unrolling (deheterochromatinization) of total heterochromatin; (b) activates synthetic processes caused by the reactivation of ribosomal genes as a result of deheterochromatinization of nucleolus organizer regions; (c) releases the genes repressed due to the condensation of euchromatic regions forming facultative heterochromatin; (d) does not induce decondensation of pericentromeric structural heterochromatin. Our results indicate that Vilon causes progressive activation (deheterochromatinization) of the facultative heterochromatin with increased aging.

Peptide Epitalon activates chromatin at the old age.

UNLABELLED: OBJECTIVES and design. We have studied the effect of synthetic peptide Epitalon on the activity of ribosomal genes, denaturation parameters of total heterochromatin, polymorphism of structural C-heterochromatin and the variability of facultative heterochromatin in cultured lymphocytes of persons aged 76-80 years. RESULTS: The obtained data demonstrate that Epitalon induces the activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin and the release of genes repressed due to the age-related condensation of euchromatic chromosome regions. CONCLUSIONS: Epitalon has shown its ability to activate chromatin by modifying heterochromatin and heterochromatinized chromosome regions in the cells of older persons.