Copy Number of Human Ribosomal Genes With Aging: Unchanged Mean, but Narrowed Range and Decreased Variance in Elderly Group
Introduction: The multi-copied genes coding for the human 18, 5.8, and 28S ribosomal RNA (rRNA) are located in five pairs of acrocentric chromosomes forming so-called rDNA. Human genome contains unmethylated, slightly methylated, and hypermethylated copies of rDNA. The major research question: What...
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2018.00306/full |
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| author | Elena M. Malinovskaya Elizaveta S. Ershova Vera E. Golimbet Lev N. Porokhovnik Nataliya A. Lyapunova Serguey I. Kutsev Natalia N. Veiko Svetlana V. Kostyuk |
| author_facet | Elena M. Malinovskaya Elizaveta S. Ershova Vera E. Golimbet Lev N. Porokhovnik Nataliya A. Lyapunova Serguey I. Kutsev Natalia N. Veiko Svetlana V. Kostyuk |
| author_sort | Elena M. Malinovskaya |
| collection | DOAJ |
| description | Introduction: The multi-copied genes coding for the human 18, 5.8, and 28S ribosomal RNA (rRNA) are located in five pairs of acrocentric chromosomes forming so-called rDNA. Human genome contains unmethylated, slightly methylated, and hypermethylated copies of rDNA. The major research question: What is the rDNA copy number (rDNA CN) and the content of hypermethylated rDNA as a function of age?Materials and Methods: We determined the rDNA CN in the blood leukocyte genomes of 651 subjects aged 17 to 91 years. The subjects were divided into two subgroups: “elderly” group (E-group, N = 126) – individuals over 72 years of age (the age of the population’s mean lifetime for Russia) and “non-elderly” group (NE-group, N = 525). The hypermethylated rDNA content was determined in the 40 DNA samples from the each group. The change in rDNA during replicative cell senescence was studied for the cultured skin fibroblast lines of five subjects from NE-group. Non-radioactive quantitative dot- and blot-hybridization techniques (NQH) were applied.Results: In the subjects from the E-group the mean rDNA CN was the same, but the range of variation was narrower compared to the NE-group: a range of 272 to 541 copies in E-group vs. 200 to 711 copies in NE-group. Unlike NE-group, the E-group genomes contained almost no hypermethylated rDNA copies. A case study of cultured skin fibroblasts from five subjects has shown that during the replicative senescence the genome lost hypermethylated rDNA copies only.Conclusion: In the elderly group, the mean rDNA CN is the same, but the range of variation is narrower compared with the younger subjects. During replicative senescence, the human fibroblast genome loses hypermethylated copies of rDNA. Two hypotheses were put forward: (1) individuals with either very low or very high rDNA content in their genomes do not survive till the age of the population’s mean lifetime; and/or (2) during the aging, the human genome eliminates hypermethylated copies of rDNA. |
| first_indexed | 2024-12-17T01:57:41Z |
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| language | English |
| last_indexed | 2024-12-17T01:57:41Z |
| publishDate | 2018-08-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-7ce24087432c4ef89853860ffa0d62842022-12-21T22:07:55ZengFrontiers Media S.A.Frontiers in Genetics1664-80212018-08-01910.3389/fgene.2018.00306397166Copy Number of Human Ribosomal Genes With Aging: Unchanged Mean, but Narrowed Range and Decreased Variance in Elderly GroupElena M. Malinovskaya0Elizaveta S. Ershova1Vera E. Golimbet2Lev N. Porokhovnik3Nataliya A. Lyapunova4Serguey I. Kutsev5Natalia N. Veiko6Svetlana V. Kostyuk7Research Centre for Medical Genetics (RCMG), Moscow, RussiaResearch Centre for Medical Genetics (RCMG), Moscow, RussiaMental Health Research Center, Moscow, RussiaResearch Centre for Medical Genetics (RCMG), Moscow, RussiaResearch Centre for Medical Genetics (RCMG), Moscow, RussiaResearch Centre for Medical Genetics (RCMG), Moscow, RussiaResearch Centre for Medical Genetics (RCMG), Moscow, RussiaResearch Centre for Medical Genetics (RCMG), Moscow, RussiaIntroduction: The multi-copied genes coding for the human 18, 5.8, and 28S ribosomal RNA (rRNA) are located in five pairs of acrocentric chromosomes forming so-called rDNA. Human genome contains unmethylated, slightly methylated, and hypermethylated copies of rDNA. The major research question: What is the rDNA copy number (rDNA CN) and the content of hypermethylated rDNA as a function of age?Materials and Methods: We determined the rDNA CN in the blood leukocyte genomes of 651 subjects aged 17 to 91 years. The subjects were divided into two subgroups: “elderly” group (E-group, N = 126) – individuals over 72 years of age (the age of the population’s mean lifetime for Russia) and “non-elderly” group (NE-group, N = 525). The hypermethylated rDNA content was determined in the 40 DNA samples from the each group. The change in rDNA during replicative cell senescence was studied for the cultured skin fibroblast lines of five subjects from NE-group. Non-radioactive quantitative dot- and blot-hybridization techniques (NQH) were applied.Results: In the subjects from the E-group the mean rDNA CN was the same, but the range of variation was narrower compared to the NE-group: a range of 272 to 541 copies in E-group vs. 200 to 711 copies in NE-group. Unlike NE-group, the E-group genomes contained almost no hypermethylated rDNA copies. A case study of cultured skin fibroblasts from five subjects has shown that during the replicative senescence the genome lost hypermethylated rDNA copies only.Conclusion: In the elderly group, the mean rDNA CN is the same, but the range of variation is narrower compared with the younger subjects. During replicative senescence, the human fibroblast genome loses hypermethylated copies of rDNA. Two hypotheses were put forward: (1) individuals with either very low or very high rDNA content in their genomes do not survive till the age of the population’s mean lifetime; and/or (2) during the aging, the human genome eliminates hypermethylated copies of rDNA.https://www.frontiersin.org/article/10.3389/fgene.2018.00306/fullribosomal DNArDNA copy numberribosomal RNAmethylated rDNAribosomal genes |
| spellingShingle | Elena M. Malinovskaya Elizaveta S. Ershova Vera E. Golimbet Lev N. Porokhovnik Nataliya A. Lyapunova Serguey I. Kutsev Natalia N. Veiko Svetlana V. Kostyuk Copy Number of Human Ribosomal Genes With Aging: Unchanged Mean, but Narrowed Range and Decreased Variance in Elderly Group Frontiers in Genetics ribosomal DNA rDNA copy number ribosomal RNA methylated rDNA ribosomal genes |
| title | Copy Number of Human Ribosomal Genes With Aging: Unchanged Mean, but Narrowed Range and Decreased Variance in Elderly Group |
| title_full | Copy Number of Human Ribosomal Genes With Aging: Unchanged Mean, but Narrowed Range and Decreased Variance in Elderly Group |
| title_fullStr | Copy Number of Human Ribosomal Genes With Aging: Unchanged Mean, but Narrowed Range and Decreased Variance in Elderly Group |
| title_full_unstemmed | Copy Number of Human Ribosomal Genes With Aging: Unchanged Mean, but Narrowed Range and Decreased Variance in Elderly Group |
| title_short | Copy Number of Human Ribosomal Genes With Aging: Unchanged Mean, but Narrowed Range and Decreased Variance in Elderly Group |
| title_sort | copy number of human ribosomal genes with aging unchanged mean but narrowed range and decreased variance in elderly group |
| topic | ribosomal DNA rDNA copy number ribosomal RNA methylated rDNA ribosomal genes |
| url | https://www.frontiersin.org/article/10.3389/fgene.2018.00306/full |
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