TUTCRIS Research Portal

TY - JOUR

T1 - Ageing-associated changes in the human DNA methylome

T2 - Genomic locations and effects on gene expression

AU - Marttila, Saara

AU - Kananen, Laura

AU - Häyrynen, Sergei

AU - Jylhävä, Juulia

AU - Nevalainen, Tapio

AU - Hervonen, Antti

AU - Jylhä, Marja

AU - Nykter, Matti

AU - Hurme, Mikko

PY - 2015/3/14

Y1 - 2015/3/14

N2 - 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.

AB - 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.

KW - Ageing

KW - DNA methylation

KW - Epigenetics

KW - Gene expression

KW - Hypermethylation

KW - Hypomethylation

KW - Methylome

KW - Molecular ageing

KW - PBMCs

UR - http://www.scopus.com/inward/record.url?scp=84928012878&partnerID=8YFLogxK

U2 - 10.1186/s12864-015-1381-z

DO - 10.1186/s12864-015-1381-z

M3 - Article

VL - 16

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 1

M1 - 179

ER -