Transcriptomics

Dataset Information

3

Tissue-specific dysregulation of DNA methylation in aging


ABSTRACT: The normal aging process is a complex phenomenon associated with physiological alterations in the function of cells and organs over time. Although an attractive candidate for mediating transcriptional dysregulation, the contribution of epigenetic dysregulation to these progressive changes in cellular function remains unclear. In this study, we employed the genome-wide HELP assay to define patterns of cytosine methylation throughout the rat genome, and the LUMA assay to measure global levels of DNA methylation in the same samples. We studied both liver and visceral adipose tissue, and demonstrated significant differences in DNA methylation with age at >5% of sites analyzed. Furthermore, we showed that epigenetic dysregulation with age is a highly tissue-dependent phenomenon. The most distinctive loci were located at intergenic sequences and conserved non-coding elements, and not at promoters nor at CG-dinucleotide dense loci. Finally, we demonstrated that changes in methylation occur consistently near genes that are involved in metabolism and metabolic regulation, implicating their potential role in the pathogenesis of age-related diseases. We conclude that different patterns of epigenetic dysregulation occur in each tissue over time and may cause some of the physiological changes associated with normal aging. Direct comparison of DNA methylation in 18 samples belonging to four groups: young liver (n=6), young adipose tissue (n=4), old liver (n=5), old adipose tissue (n=3), isolated from F344*BN rats (young at ~3 months, old at ~18 months). Each microarray consists of a two-color comparison of a methylation-sensitive representation of the genome (HpaII) with an internal methylation-insensitive control/reference (MspI).

ORGANISM(S): Rattus norvegicus  

SUBMITTER: Nir Barzilai   Gil Atzmon  Christina Lowes  Reid F Thompson  Hong Q Liang  John M Greally 

PROVIDER: E-GEOD-17332 | ArrayExpress | 2010-05-01

SECONDARY ACCESSION(S): GSE17332PRJNA119017

REPOSITORIES: GEO, ArrayExpress

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Publications

Tissue-specific dysregulation of DNA methylation in aging.

Thompson Reid F RF   Atzmon Gil G   Gheorghe Ciprian C   Liang Hong Qian HQ   Lowes Christina C   Greally John M JM   Barzilai Nir N  

Aging cell 20100522 4


The normal aging process is a complex phenomenon associated with physiological alterations in the function of cells and organs over time. Although an attractive candidate for mediating transcriptional dysregulation, the contribution of epigenetic dysregulation to these progressive changes in cellular physiology remains unclear. In this study, we employed the genome-wide HpaII tiny fragment enrichment by ligation-mediated PCR assay to define patterns of cytosine methylation throughout the rat gen  ...[more]

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