title: High preservation of CpG cytosine methylation patterns at imprinted gene loci in liver and brain of aged mice.
abstract: A gradual loss of the correct patterning of 5-methyl cytosine marks in gene promoter regions has been implicated in aging and age-related diseases, most notably cancer. While a number of studies have examined DNA methylation in aging, there is no consensus on the magnitude of the effects, particularly at imprinted loci. Imprinted genes are likely candidate to undergo age-related changes because of their demonstrated plasticity in utero, for example, in response to environmental cues. Here we quantitatively analyzed a total of 100 individual CpG sites in promoter regions of 11 imprinted and non-imprinted genes in liver and cerebral cortex of young and old mice using mass spectrometry. The results indicate a remarkably high preservation of methylation marks during the aging process in both organs. To test if increased genotoxic stress associated with premature aging would destabilize DNA methylation we analyzed two DNA repair defective mouse models showing a host of premature aging symptoms in liver and brain. However, also in these animals, at the end of their life span, we found a similarly high preservation of DNA methylation marks. We conclude that patterns of DNA methylation in gene promoters of imprinted genes are surprisingly stable over time in normal, postmitotic tissues and that the multiple documented changes with age are likely to involve exceptions to this pattern, possibly associated with specific cellular responses to age-related changes other than genotoxic stress.
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, New York, New York, United States of America.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gravina
authors.forename: Martijn E T
authors.initials: ME
authors.lastname: Dollé
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Harry
authors.initials: H
authors.lastname: van Steeg
authors.forename: Paul
authors.initials: P
authors.lastname: Hasty
authors.forename: Jan
authors.initials: J
authors.lastname: Hoeijmakers
authors.forename: Jan
authors.initials: J
authors.lastname: Vijg
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism*; D018899:CpG Islands; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation; D004260:DNA Repair; D056426:Genetic Loci; D018392:Genomic Imprinting; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic
chemical_list: D003596:Cytosine
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