The transcription of ribosomal RNA genes (rDNA) is subject to epigenetic regulation, as it is abrogated by the methylation of CpG dinucleotides within their promoter region. Here, we investigated, through Sequenom platform, the age-related methylation status of the CpG island falling into the rDNA promoter in 472 blood samples from 20-105 years old humans and indifferent tissues (blood, heart, liver, kidney and testis) of 15 rats 3-96 weeks old. In humans, we did not find a statistically significant correlation between CpG sites and chronological age (although data showed a weak tendency to such correlation). However, the methylation levels of one of the analyzed CpG sites were negatively associated with both cognitive performance and survival chance measured in a 9 years follow up study. We confirmed such result by both Bonferroni test and a replication in an independent sample. The analysis of the homologous region in tissues fromrats of different ages revealed the existence of increased methylation in old rats. rRNA expression data, in both humans and rats, were consistent with methylation patterns, with a lower expression ofrRNA in highly methylated subjects. As chronological and biological ages in rats of a given strain are likely to be much closer to each other than in humans, these results seem to provide the first evidence that epigenetic modifications of rDNA change over time according to the aging decline. Thus, the methylation profile of rDNAmay represent a potential biomarker of aging

The transcription of ribosomal RNA genes (rDNA) is subject to epigenetic regulation, as it is abrogated by the methylation of CpGdinucleotides within their promoter region. Here, we investigated, through Sequenom platform, the age-related methylation status of the CpGisland falling into the rDNA promoter in 472 blood samples from 20-105 years old humans and in different tissues (blood, heart, liver, kidney and testis) of 15 rats 3-96 weeks old. In humans, we did not find a statistically significant correlation between CpG sites and chronological age (although data showed a weak tendency to such correlation). However, the methylation levels of one of the analyzed CpG sites were negatively associated with both cognitive performance and survival chance measured in a 9 years follow up study. We confirmed such result by both Bonferroni test and a replication in an independent sample. The analysis of the homologous region in tissues from rats of different ages revealed the existence of increased methylation in old rats. rRNA expression data, in both humans and rats, were consistent with methylation patterns, with a lower expression of rRNA in highly methylated subjects.As chronological and biological ages in rats of a given strain are likely to be much closer to each other than in humans, these results seem to provide the first evidence that epigenetic modifications of rDNA change over time according to the aging decline. Thus, the methylation profile of rDNA may represent a potential biomarker of aging.

Methylation of the ribosomal RNA gene promoter is associated with aging and age related decline

D’Aquila P;MONTESANTO, Alberto;MANDALA', Maurizio;BELLIZZI, Dina;Passarino G.
2017

Abstract

The transcription of ribosomal RNA genes (rDNA) is subject to epigenetic regulation, as it is abrogated by the methylation of CpGdinucleotides within their promoter region. Here, we investigated, through Sequenom platform, the age-related methylation status of the CpGisland falling into the rDNA promoter in 472 blood samples from 20-105 years old humans and in different tissues (blood, heart, liver, kidney and testis) of 15 rats 3-96 weeks old. In humans, we did not find a statistically significant correlation between CpG sites and chronological age (although data showed a weak tendency to such correlation). However, the methylation levels of one of the analyzed CpG sites were negatively associated with both cognitive performance and survival chance measured in a 9 years follow up study. We confirmed such result by both Bonferroni test and a replication in an independent sample. The analysis of the homologous region in tissues from rats of different ages revealed the existence of increased methylation in old rats. rRNA expression data, in both humans and rats, were consistent with methylation patterns, with a lower expression of rRNA in highly methylated subjects.As chronological and biological ages in rats of a given strain are likely to be much closer to each other than in humans, these results seem to provide the first evidence that epigenetic modifications of rDNA change over time according to the aging decline. Thus, the methylation profile of rDNA may represent a potential biomarker of aging.
The transcription of ribosomal RNA genes (rDNA) is subject to epigenetic regulation, as it is abrogated by the methylation of CpG dinucleotides within their promoter region. Here, we investigated, through Sequenom platform, the age-related methylation status of the CpG island falling into the rDNA promoter in 472 blood samples from 20-105 years old humans and indifferent tissues (blood, heart, liver, kidney and testis) of 15 rats 3-96 weeks old. In humans, we did not find a statistically significant correlation between CpG sites and chronological age (although data showed a weak tendency to such correlation). However, the methylation levels of one of the analyzed CpG sites were negatively associated with both cognitive performance and survival chance measured in a 9 years follow up study. We confirmed such result by both Bonferroni test and a replication in an independent sample. The analysis of the homologous region in tissues fromrats of different ages revealed the existence of increased methylation in old rats. rRNA expression data, in both humans and rats, were consistent with methylation patterns, with a lower expression ofrRNA in highly methylated subjects. As chronological and biological ages in rats of a given strain are likely to be much closer to each other than in humans, these results seem to provide the first evidence that epigenetic modifications of rDNA change over time according to the aging decline. Thus, the methylation profile of rDNAmay represent a potential biomarker of aging
ribosomal RNA (rRNA) genes, ribosomal DNA (rDNA) promoter, aging, geriatric parameters, chronological age, biological age
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11770/133951
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