Age-And Gender-Related Pattern of Methylation in the MT-RNR1 Gene

Abstract

Aim: We evaluated the methylation of two CpG sites located within human mitochondrial 12S and 16S ribosomal RNA (MT-RNR1 and MT-RNR2) genes. Materials & methods: Methylation was measured through bisulfite sequencing and qPCR assays on DNA samples collected from 381 differently aged human subjects. Results: Analyses revealed the methylation of the site in the MT-RNR1 gene and the co-presence of both unmethylated and methylated cytosines in most samples. High methylation levels (>10%) were more frequent in old women with respect to younger controls. A 9-year-long follow-up survey showed that subjects with high methylation levels exhibit a mortality risk significantly higher than subjects with low levels. Conclusion: Our data further support the presence of methylation within human mitochondrial DNA and suggest that high levels of methylation of the MT-RNR1 site may reflect a condition of the cell or of the organism unfavorable to survival.

Keywords::

• 12S ribosomal RNA gene
• 12S ribosomal RNA gene methylation
• 16S ribosomal RNA gene
• aging
• DNA methylation
• mitochondrial DNA
• MT-RNR1 gene
• mortality risk

Financial & competing interests disclosure

The research leading to these results has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2011) under grant agreement number 259679 and from Programma Operativo Nazionale (01_00937) – MIUR “Modelli sperimentali biotecnologici integrati per lo sviluppo e la selezione di molecole di interesse per la salute dell’uomo.” The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate insti­tutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The research leading to these results has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2011) under grant agreement number 259679 and from Programma Operativo Nazionale (01_00937) – MIUR “Modelli sperimentali biotecnologici integrati per lo sviluppo e la selezione di molecole di interesse per la salute dell’uomo.” The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.