Effect of the peptide bronchogen (Ala-Asp-Glu-Leu) on DNA thermostability

Thermodynamic parameters of DNA melting in the presence of a peptide bronchogen in various concentrations were estimated on a differential scanning microcalorimeter. Bronchogen was shown to serve as a DNA-stabilizing agent. Bronchogen increased the melting temperature of DNA from calf thymus and mouse liver by 3.1°C in a narrow range of r (molar ratio of bronchogen/DNA b.p., 0.01-0.055). A further increase in r was not accompanied by changes in the melting temperature. The complex melting enthalpy (ΔH_melt) remained unchanged in this range of r (0.01-1.0). ΔH_melt for DNA from the thymus and mouse liver was 11.4 and 12.7 cal/g, respectively. Our results indicate that bronchogen is not an adenine–thymine-specific or guanine–cytosine-specific ligand. The type of binding is considered as strong and occasional. The binding occurs with both strands of DNA (mainly with nitrogen bases).     

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.     

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.     

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.     

Effects of Livagen peptide on chromatin activation in lymphocytes from old people

We studied the effects of the synthetic peptide Livagen on activity of ribosomal genes, denaturation parameters of heterochromatin, polymorphism of structural C-heterochromatin, and variability of facultative heterochromatin in lymphocytes from old people. Livagen induced activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin, and release of genes repressed due to age-related condensation of euchromatic regions in chromosomes. Our results indicate that Livagen causes de-heterochromatinization (activation) of chromatin, which is realized via modification of heterochromatin and heterochromatinized regions in chromosomes from old people.