Journal
JOURNAL OF NUTRITION
Volume 132, Issue 8, Pages 2388S-2392SPublisher
OXFORD UNIV PRESS
DOI: 10.1093/jn/132.8.2388S
Keywords
epigenetics; DNA methylation; aging; CpG islands; CpG island methylator phenotype
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Cytosine guanine dinucleotide (CpG) island methylation is a known mechanism of epigenetic inheritance in postmeiotic cells. Through associated chromatin changes and silencing such epigenetic states can influence cellular physiology and affect disease risk and severity. Our studies of CpG island methylation in normal colorectal mucosa revealed progressive age-related increases at multiple gene loci, suggesting genome-wide molecular alterations with potential to silence gene expression. However, there was considerable variation in the degree of methylation among individuals of comparable ages. Such variation could be related to genetic factors, lifestyle, or environmental exposures. Studies in ulcerative colitis and hepatocellular cirrhosis and neoplasia revealed that chronic inflammatory states are accompanied by marked increases in CpG island methylation in normal-appearing tissues, confirming the hypothesis that proinflammatory exposures could account for part of the epigenetic variation in human populations. Preliminary data also suggest potential influences of lifestyle and exposure factors on CpG island methylation. It is suggested that epigenetic variation related to aging lifestyle, exposures and possibly genetic factors, is one of the modulators of acquired, age-related human diseases, including neoplasia.
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