RT Journal
A1 Rakyan, Vardhman K.
A1 Down, Thomas A.
A1 Maslau, Siarhei
A1 Andrew, Toby
A1 Yang, Tsun-Po
A1 Beyan, Huriya
A1 Whittaker, Pamela
A1 McCann, Owen T.
A1 Finer, Sarah
A1 Valdes, Ana M.
A1 Leslie, R. David
A1 Deloukas, Panogiotis
A1 Spector, Timothy D.
T1 Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains
JF Genome Research 
JO Genome Research 
YR 2010 
FD April 01 
VO 20 
IS 4 
SP 434 
OP 439 
DO 10.1101/gr.103101.109 
UL http://genome.cshlp.org/content/20/4/434.abstract 
AB There is a growing realization that some aging-associated phenotypes/diseases have an epigenetic basis. Here, we report the first genome-scale study of epigenomic dynamics during normal human aging. We identify aging-associated differentially methylated regions (aDMRs) in whole blood in a discovery cohort, and then replicate these aDMRs in sorted CD4+ T-cells and CD14+ monocytes in an independent cohort, suggesting that aDMRs occur in precursor haematopoietic cells. Further replication of the aDMRs in buccal cells, representing a tissue that originates from a different germ layer compared with blood, demonstrates that the aDMR signature is a multitissue phenomenon. Moreover, we demonstrate that aging-associated DNA hypermethylation occurs predominantly at bivalent chromatin domain promoters. This same category of promoters, associated with key developmental genes, is frequently hypermethylated in cancers and in vitro cell culture, pointing to a novel mechanistic link between aberrant hypermethylation in cancer, aging, and cell culture.