Age-and gender-related pattern of methylation in the MT-RNR1 gene

Epigenomics. 2015 Aug;7(5):707-16. doi: 10.2217/epi.15.30. Epub 2015 Sep 7.

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; DNA methylation; MT-RNR1 gene; aging; mitochondrial DNA; mortality risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • CpG Islands / genetics
  • DNA Methylation*
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / genetics*
  • Female
  • Gene Frequency
  • Genes, Mitochondrial / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Proportional Hazards Models
  • RNA, Ribosomal / genetics*
  • RNA, Ribosomal, 16S / genetics*
  • Sequence Analysis, DNA / methods
  • Sequence Analysis, DNA / statistics & numerical data
  • Sex Factors

Substances

  • DNA, Mitochondrial
  • RNA, Ribosomal
  • RNA, Ribosomal, 16S
  • RNA, ribosomal, 12S