title: Ageing-associated changes in the human DNA methylome: genomic locations and effects on gene expression.
abstract: BACKGROUND
  Changes in DNA methylation are among the mechanisms contributing to the ageing process. We sought to identify ageing-associated DNA methylation changes at single-CpG-site resolution in blood leukocytes and to ensure that the observed changes were not due to differences in the proportions of leukocytes. The association between DNA methylation changes and gene expression levels was also investigated in the same individuals.
  
  
  RESULTS
  We identified 8540 high-confidence ageing-associated CpG sites, 46% of which were hypermethylated in nonagenarians. The hypermethylation-associated genes belonged to a common category: they were predicted to be regulated by a common group of transcription factors and were enriched in a related set of GO terms and canonical pathways. Conversely, for the hypomethylation-associated genes only a limited set of GO terms and canonical pathways were identified. Among the 8540 CpG sites associated with ageing, methylation level of 377 sites was also associated with gene expression levels. These genes were enriched in GO terms and canonical pathways associated with immune system functions, particularly phagocytosis.
  
  
  CONCLUSIONS
  We find that certain ageing-associated immune-system impairments may be mediated via changes in DNA methylation. The results also imply that ageing-associated hypo- and hypermethylation are distinct processes: hypermethylation could be caused by programmed changes, whereas hypomethylation could be the result of environmental and stochastic processes.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland. saara.marttila@uta.fi.|Gerontology Research Center, Tampere, Finland. saara.marttila@uta.fi.
authors.forename: Saara
authors.initials: S
authors.lastname: Marttila
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland. laura.kananen@uta.fi.|Gerontology Research Center, Tampere, Finland. laura.kananen@uta.fi.
authors.forename: Laura
authors.initials: L
authors.lastname: Kananen
authors.affiliation: Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland. sergei.hayrynen@tut.fi.
authors.forename: Sergei
authors.initials: S
authors.lastname: Häyrynen
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland. juulia.jylhava@uta.fi.|Gerontology Research Center, Tampere, Finland. juulia.jylhava@uta.fi.
authors.forename: Juulia
authors.initials: J
authors.lastname: Jylhävä
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland. tapio.l.nevalainen@uta.fi.|Gerontology Research Center, Tampere, Finland. tapio.l.nevalainen@uta.fi.
authors.forename: Tapio
authors.initials: T
authors.lastname: Nevalainen
authors.affiliation: Gerontology Research Center, Tampere, Finland. antti.hervonen@uta.fi.|School of Health Sciences, University of Tampere, Tampere, Finland. antti.hervonen@uta.fi.
authors.forename: Antti
authors.initials: A
authors.lastname: Hervonen
authors.affiliation: Gerontology Research Center, Tampere, Finland. marja.jylha@uta.fi.|School of Health Sciences, University of Tampere, Tampere, Finland. marja.jylha@uta.fi.
authors.forename: Marja
authors.initials: M
authors.lastname: Jylhä
authors.affiliation: Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland. matti.nykter@uta.fi.
authors.forename: Matti
authors.initials: M
authors.lastname: Nykter
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland. mikko.a.hurme@uta.fi.|Gerontology Research Center, Tampere, Finland. mikko.a.hurme@uta.fi.|Fimlab Laboratories, Tampere, Finland. mikko.a.hurme@uta.fi.
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D015894:Genome, Human; D006801:Humans; D008297:Male; D058977:Molecular Sequence Annotation; D012737:Sex Factors