Abstract
Epigenetic changes are widely considered to play an important role in aging, but experimental evidence to support this hypothesis has been scarce. We have used array-based analysis to determine genome-scale DNA methylation patterns from human skin samples and to investigate the effects of aging, chronic sun exposure, and tissue variation. Our results reveal a high degree of tissue specificity in the methylation patterns and also showed very little interindividual variation within tissues. Data stratification by age revealed that DNA from older individuals was characterized by a specific hypermethylation pattern affecting less than 1% of the markers analyzed. Interestingly, stratification by sun exposure produced a fundamentally different pattern with a significant trend towards hypomethylation. Our results thus identify defined age-related DNA methylation changes and suggest that these alterations might contribute to the phenotypic changes associated with skin aging.
Highlights
Aging is defined by characteristic phenotypic changes, but there appear to be few corresponding changes in the genotype
A role of epigenetic mechanisms in aging and in the adaptation to environmental exposures has been widely assumed, research in this area has been hampered by major methodological challenges
We have used a novel platform for genome-scale methylation analysis to determine the methylation patterns of human skin samples
Summary
Aging is defined by characteristic phenotypic changes, but there appear to be few corresponding changes in the genotype. Epigenetic mechanisms regulate the interpretation of genetic information and have the ability to produce different phenotypes from a single genotype [2]. The corresponding regulatory mechanisms are based on two independent modification systems, the covalent modification of histones and the methylation of cytosine residues in DNA [3]. Over the past few years, numerous histone modifications have been described and it has been suggested that complex histone modification patterns encode detailed information about the regulation of associated genes and promoters [4]. The methylation status of a gene promoter can have an important effect on the activity status of the corresponding gene and hypermethylation-associated silencing of tumor suppressor genes has been shown to play a prominent role in human cancers [5]
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