Age-and gender-related pattern of methylation in the MT-RNR1 gene.
OBJECTIVE
We evaluated the methylation of two CpG sites located within human mitochondrial 12S and 16S ribosomal RNA (MT-RNR1 and MT-RNR2) genes.


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.


CONCLUSIONS
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.
Department of Biology, Ecology & Earth Science (DIBEST), University of Calabria, 87036 Rende, Italy.
Patrizia
P
D'Aquila
Department of Biology, Ecology & Earth Science (DIBEST), University of Calabria, 87036 Rende, Italy.
Marco
M
Giordano
Department of Biology, Ecology & Earth Science (DIBEST), University of Calabria, 87036 Rende, Italy.
Alberto
A
Montesanto
Department of Biology, Ecology & Earth Science (DIBEST), University of Calabria, 87036 Rende, Italy.
Francesco
F
De Rango
Department of Biology, Ecology & Earth Science (DIBEST), University of Calabria, 87036 Rende, Italy.
Giuseppe
G
Passarino
Department of Biology, Ecology & Earth Science (DIBEST), University of Calabria, 87036 Rende, Italy.
Dina
D
Bellizzi
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D050259:Genes, Mitochondrial / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D012335:RNA, Ribosomal / Q000235:genetics*; D012336:RNA, Ribosomal, 16S / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods / Q000706:statistics & numerical data; D012737:Sex Factors
D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; D012336:RNA, Ribosomal, 16S; C075526:RNA, ribosomal, 12S
12S ribosomal RNA gene; 12S ribosomal RNA gene methylation; 16S ribosomal RNA gene; DNA methylation; MT-RNR1 gene; aging; mitochondrial DNA; mortality risk