Blood DNA Methylation and Aging: A Cross-Sectional Analysis and Longitudinal Validation in the InCHIANTI Study.
Changes in DNA methylation have been found to be highly correlated with aging in humans, but causes or consequences of these changes are not understood. We characterized the DNA methylomes of several hundred people in the Invecchiare in Chianti study to identify DNA sites in which percent methylation was systematically different with age. Then, we tested the hypothesis that changes of percent methylation in the same DNA sites occur longitudinally for the same DNA sites in the same subjects. We identified six differentially methylated regions in which percent methylation showed robust longitudinal changes in the same direction. We then describe functions of the genes near these differentially methylated regions and their potential relationship with aging, noting that the genes appear to regulate metabolism or cell type specificity. The nature of transcription factor binding sites in the vicinity of these differentially methylated regions suggest that these age-associated methylation changes reflect modulation of two biological mechanisms: the polycomb repressive complex 2, a protein complex that trimethylates histone H3 on lysine 27, and the transcriptional repressor CCCTC-binding factor or CTCF, both of which are regulators of chromatin architecture. These findings are consistent with the idea that changes in methylation with aging are of adaptive nature.
['Tharakan|Ravi|R|', 'Ubaida-Mohien|Ceereena|C|', 'Moore|Ann Zenobia|AZ|', 'Hernandez|Dena|D|', 'Tanaka|Toshiko|T|', 'Ferrucci|Luigi|L|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000375:Aging D000076246:CCCTC-Binding Factor D018899:CpG Islands D003430:Cross-Sectional Studies D004247:DNA D019175:DNA Methylation D057890:Epigenomics D005260:Female D006801:Humans D007558:Italy D008137:Longitudinal Studies D008297:Male D008875:Middle Aged D011446:Prospective Studies D011485:Protein Binding D014157:Transcription Factors
DNA methylation Epigenetics Epigenetics of aging Epigenomics Longitudinal epigenomics