Bioregulator Vilon-Induced Reactivation of Chromatin in Cultured Lymphocytes from Old People

Lezhava, Teimuraz; Khavison, Vladimir; Monaselidze, Jamlet; Jokhadze, T; Dvalishvili, Nana; Bablishvili, N. K.; Barbakadze, Shota

doi:10.1023/b:bgen.0000025070.90330.7f

Cited by 9 publications

(7 citation statements)

References 19 publications

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“…In the context of heterochromatinization decreased intensity of reparation and elevated rate of mutations in the elderly are considered to be secondary 2,3 . Reactivation (decondensation) of the heterochromatinized regions in human's lymphocyte cultures induced by the peptide bioregulators has been detected 3,7,16,25,26 . Current data correspond to our findings using DMC method: lymphocytes from old individuals had increased chromosome heterochromatinization and the peptide bioregulator Livagen significantly induced reactivation of these chromosome alterations possibly by decondensation of 10‐nm filaments.…”

Section: Results and Discusionsupporting

confidence: 89%

“…Heavy metals affecting the human genome and provoking the development of different senile pathological processes 4,5 provide an extended area for scientific research aimed at detecting the means contributing to enhanced stability of the organism. Synthetic peptide bioregulators, retarding aging rate as well as decreasing the risk of development senile pathologies are currently efficiently applied to regulate the aging process 6,7 …”

Section: Introductionmentioning

confidence: 99%

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

Lezhava

Jokhadze

2007

Annals of the New York Academy of Sciences

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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.

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Section: Results and Discusionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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

Lezhava

Jokhadze

2007

Annals of the New York Academy of Sciences

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“…The importance of stable pericentromeric DNA methylation for normal chromosome segregation has been underscored by several recent discoveries. For example, lymphocytes from individuals with the rare autosomal disorder ICF (immunodeficiency, centromeric instability, and facial anomalies) exhibit profound chromosomal abnormalities, including selective undermethylation of pericentromeric satellite DNA, chromosome decondensation, and complex multiradiate chromosomes (Lezhava et al, 2004). The genetic origin of this disorder was recently discovered to be a mutation in the de novo DNA methyltransferase 3B (DNMT3B) and supports a causal association between DNA hypomethylation, pericentromeric decondensation, and abnormal chromosome segregation (Geiman et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China

Wang

Qiao

et al. 2008

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), the central enzymes in folate metabolism that affects DNA methylation and synthesis, and the risk of Down syndrome in China. Methods: Genomic DNA was isolated from the peripheral lymphocytes of 64 mothers of children with Down syndrome and 70 age matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C→T, MTRR 66A→G and the relationship between these genotypes and the risk of Down syndrome was analyzed. Results: The results show that the MTHFR 677C→T polymorphism is more prevalent among mothers of children with Down syndrome than among control mothers, with an odds ratio of 3.78 (95% confidence interval (CI), 1.78~8.47). In addition, the homozygous MTRR 66A→G polymorphism was independently associated with a 5.2-fold increase in estimated risk (95% CI, 1.90~14.22). The combined presence of both polymorphisms was associated with a greater risk of Down syndrome than the presence of either alone, with an odds ratio of 6.0 (95% CI, 2.058~17.496). The two polymorphisms appear to act without a multiplicative interaction. Conclusion: MTHFR and MTRR gene mutation alleles are related to Down syndrome, and CT, TT and GG gene mutation types increase the risk of Down syndrome.

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“…In the respect, it should be noted that heterochromatinized regions in chromosomes can reverse. Many physical and chemical agents, hormones and peptide bioregulators cause deheterochromatinization (decondensation) (Khavinson et al 2002, 2003; Lezhava and Bablishvili 2003; Lezhava et al 2004). Such actions may be helpful in the treatment of diseases of aging.…”

Section: Heterochromatin and Pathologymentioning

confidence: 99%

Gerontology research in Georgia

Lezhava

Monaselidze²,

Jokhadze

et al. 2010

Biogerontology

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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.

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Bioregulator Vilon-Induced Reactivation of Chromatin in Cultured Lymphocytes from Old People

Cited by 9 publications

References 19 publications

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

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

Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China

Gerontology research in Georgia

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