title: Age-associated changes in DNA methylation across multiple tissues in an inbred mouse model.
abstract: Epigenetic disruption has been implicated in many diseases of aging, and age-associated DNA methylation changes at specific genomic loci in humans are strongly correlated with chronological age. The aim of this study was to explore the specificity of selected age-associated differentially methylated positions (aDMPs) identified in human epidemiological studies by quantifying DNA methylation across multiple tissues in homologous regions of the murine genome. We selected four high-confidence aDMPs (located in the vicinity of the ELOVL2, GLRA1, MYOD1 and PDE4C genes) and quantified DNA methylation across these regions in four tissues (blood, lung, cerebellum and hippocampus) from male and female C57BL/6J mice, ranging in age from fetal (embryonic day 17) to 630 days. We observed tissue-specific age-associated changes in DNA methylation that was directionally consistent with those observed in humans. These findings lend further support to the notion that changes in DNA methylation are associated with chronological age and suggest that these processes are often conserved across tissues and between mammalian species. Our data highlight the relevance of utilizing model systems, in which environmental and genetic influences can be carefully controlled, for the further study of these phenomena.
authors: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK. Electronic address: helen.h.spiers@kcl.ac.uk.
authors: Helen
authors: H
authors: Spiers
authors: University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK. Electronic address: e.j.hannon@exeter.ac.uk.
authors: Eilis
authors: E
authors: Hannon
authors: Mary Lyon Centre, Harwell, Didcot, Oxfordshire OX11 ORD, UK. Electronic address: s.wells@har.mrc.ac.uk.
authors: Sara
authors: S
authors: Wells
authors: Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK. Electronic address: brenda.p.willams@kcl.ac.uk.
authors: Brenda
authors: B
authors: Williams
authors: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK. Electronic address: catherine.fernandes@kcl.ac.uk.
authors: Cathy
authors: C
authors: Fernandes
authors: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK; University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK. Electronic address: j.mill@exeter.ac.uk.
authors: Jonathan
authors: J
authors: Mill
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008954:Models, Biological; D009928:Organ Specificity / Q000502:physiology
keywords: Aging; Cross-tissue; DNA methylation; Epigenetics; Inbred mouse