Abstract
BackgroundAging and sun exposure are the leading causes of skin cancer. It has been shown that epigenetic changes, such as DNA methylation, are well established mechanisms for cancer, and also have emerging roles in aging and common disease. Here, we directly ask whether DNA methylation is altered following skin aging and/or chronic sun exposure in humans.ResultsWe compare epidermis and dermis of both sun-protected and sun-exposed skin derived from younger subjects (under 35 years old) and older subjects (over 60 years old), using the Infinium HumanMethylation450 array and whole genome bisulfite sequencing. We observe large blocks of the genome that are hypomethylated in older, sun-exposed epidermal samples, with the degree of hypomethylation associated with clinical measures of photo-aging. We replicate these findings using whole genome bisulfite sequencing, comparing epidermis from an additional set of younger and older subjects. These blocks largely overlap known hypomethylated blocks in colon cancer and we observe that these same regions are similarly hypomethylated in squamous cell carcinoma samples.ConclusionsThese data implicate large scale epigenomic change in mediating the effects of environmental damage with photo-aging.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0644-y) contains supplementary material, which is available to authorized users.
Highlights
Aging and sun exposure are the leading causes of skin cancer
We undertook a comprehensive genome-wide analysis of DNA methylation in human skin to test for alterations associated with age or with sun exposure, and the potential relationship between these regions
To explore how genetic diversity may relate to the observed hypomethylated blocks in aged, sun-exposed skin, we examined signal at 65 single nucleotide polymorphism (SNP) probes included on the 450k array
Summary
Aging and sun exposure are the leading causes of skin cancer. It has been shown that epigenetic changes, such as DNA methylation, are well established mechanisms for cancer, and have emerging roles in aging and common disease. We directly ask whether DNA methylation is altered following skin aging and/or chronic sun exposure in humans. There is a growing realization that environmental factors are major contributors to aging and ageassociated illness. Epigenetics is the study of chemical modifications of the genome, heritable by cell progeny, and it has been an attractive target for studies of aging and environmentally influenced disease. The skin as a model of aging offers the advantage of studying the influence of environmental factors by virtue of its direct exposure to the sun. Skin affords the ability to compare the effects of intrinsic and extrinsic (environmental) aging through the comparison of chronically sun-exposed (for example, forearm and face) and sun-protected skin
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