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Updated: Apr 14, 2026
Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin
Amy R Vandiver1, Rafael A Irizarry2,3, Kasper D Hansen4,5
1Center for Epigenetics, Johns Hopkins University School of Medicine, Rangos 570, 855N. Wolfe St, Baltimore, MD, 21205, USA. aunterm1@jhmi.edu.
Background:
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.
Results:
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.
Conclusions:
These data implicate large scale epigenomic change in mediating the effects of environmental damage with photo-aging.
Insights
Skin aging and sun exposure alter DNA methylation patterns, particularly in sun-exposed skin. These epigenetic changes in skin aging are linked to photo-aging and overlap with cancer-related methylation changes.
Area of Science:
- Epigenetics
- Dermatology
- Genomics
Background:
- Aging and sun exposure are primary drivers of skin cancer.
- Epigenetic alterations, including DNA methylation, are implicated in aging, common diseases, and cancer.
- The study investigates DNA methylation changes in human skin due to aging and sun exposure.
Purpose of the Study:
- To determine if DNA methylation patterns are altered in human skin by aging and/or chronic sun exposure.
- To compare methylation profiles in different skin layers (epidermis and dermis) and between younger and older individuals.
- To correlate observed methylation changes with clinical signs of photo-aging.
Main Methods:
- Comparison of epidermis and dermis from sun-protected and sun-exposed skin of younger (<35 years) and older (>60 years) subjects.
- Utilized Infinium HumanMethylation450 array and whole genome bisulfite sequencing.
- Replication of findings using whole genome bisulfite sequencing on additional epidermal samples.
Main Results:
- Identified large genomic blocks that are hypomethylated in older, sun-exposed epidermal samples.
- The extent of hypomethylation correlated with clinical measures of photo-aging.
- These hypomethylated regions in aged, sun-exposed skin overlap with those found in colon cancer and squamous cell carcinoma.
Conclusions:
- Large-scale epigenomic changes are involved in the effects of environmental damage, specifically photo-aging.
- DNA methylation alterations in skin are associated with aging and sun exposure.
- The findings suggest a link between environmentally induced epigenetic changes and skin cancer development.
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