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 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.,We 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.,These data implicate large scale epigenomic change in mediating the effects of environmental damage with photo-aging.,The online version of this article (doi:10.1186/s13059-015-0644-y) contains supplementary material, which is available to authorized users.
It has been hypothesised that light skin pigmentation has arisen to ensure adequate levels of vitamin D as human populations moved out of Africa and into higher latitudes.,Vitamin D, which is primarily obtained through exposure to sunlight (specifically ultraviolet radiation B (UVR-B)), has been inversely associated with several complex diseases.,Greater sun exposure, on the other hand, is a well-known cause of skin cancer.,The potential of UVR to be beneficial for some health outcomes but detrimental for others has prompted a public health debate on how to balance the positive and negative consequences of sun exposure.,In this study we aimed to determine the validity of the evolutionary hypothesis linking lighter skin with higher vitamin D concentrations in a European population.,Additionally, we aimed to examine the influence of pigmentation on personal behaviour towards sunlight exposure and the effects of this behaviour on vitamin D.,We combined genetic variants strongly associated with skin colour, tanning or freckling to create genetic scores for each of these phenotypes.,We examined the association of the scores with pigmentary traits, sun exposure and serum 25-hydroxyvitamin D (25(OH)D) levels among children of the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 661 to 5649).,We found that fairer-skinned children, i.e. those with higher pigmentation score values, had higher levels of 25(OH)D (0.6 nmol/l; 95% CI 0.2, 1.0; per unit increase in skin colour score; N = 5649).,These children also used more protection against the damaging effects of UVR.,In this population taking protective measures against sunburn and skin cancer does not seem to remove the positive effect that having a less pigmented skin has on vitamin D production.,Our findings require further replication as skin pigmentation showed only a small effect on circulating 25(OH)D.