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I.R.F. / Aging news / Diseases / 10072802

DNA Methylation in Aging Causes Tissue-specific Dysregulation
Posted on: July 28, 2010

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.

Scientists employed the genome-wide HpaII tiny fragment enrichment by ligation-mediated PCR assay to define patterns of cytosine methylation throughout the rat genome and the luminometric methylation analysis assay to measure global levels of DNA methylation in the same samples. They studied both liver and visceral adipose tissues and demonstrated significant differences in DNA methylation with age at > 5% of sites analyzed. Furthermore, they showed that epigenetic dysregulation with age is a highly tissue-dependent phenomenon.

The most distinctive loci were located at intergenic sequences and conserved noncoding elements, and not at promoters nor at CG-dinucleotide-dense loci. Despite this, they found that there was a subset of genes at which cytosine methylation and gene expression changes were concordant.

Finally, they 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.

So they 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.

Source: Thompson RF, Atzmon G, Gheorghe C, Liang HQ, Lowes C, Greally JM, Barzilai N.; Tissue-specific dysregulation of DNA methylation in aging.; Aging Cell. 2010 Aug;9(4):506-18. Epub 2010 May 22.
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