As we approach the beginning of summer, many will be looking forward to time in the warm sun. But summertime is also the season to think about the possible effects of long-term sun exposure. Soaking up the sun may have positive effects on our vacation plans, but the effects on our skin aren't often as kind, especially as we grow older. So scientists set out to answer the following question: "As we enjoy our fun in the sun, how is our skin responding while we age?"
To help answer this, a group of scientists led by Andrew P. Feinberg, M.D., at the John Hopkins School of Medicine, have compared genomic information in both sun-exposed and sun-protected skin in younger and older individuals. The April Genome Advance of the Month describes the results of these comparisons, and what this suggests for the changes our skin undergoes as a result of sun exposure and aging. These results - understanding the relationship between skin cancer, sun exposure and aging - will perhaps eventually enable scientists and clinicians to target the cellular pathways causing skin cancer and create new therapies.
Aging and sun exposure have long been linked to skin cancer, but the mechanism responsible - how exactly that happens - remained unknown. Scientists began to wonder if perhaps epigenetics could be the culprit behind skin cancer. In fact, epigenetic changes have previously been linked to several other types of cancer, so looking at epigenetic changes seemed to be a good place to start investigating.
Epigenetics is a field of science that studies chemical changes to the genome (changes that leave the sequence of As, Ts, Cs, and Gs the same). These changes can affect how genes are regulated - i.e. turned on or off. By modifying the genome, epigenetic compounds tell our cells and tissues when, what and where genes need to be active in the human body. They also tell genes when they are not needed and can be deactivated. Epigenetic changes are important because they help specialize cells and tissues to their specific functions. For example, a skin cell is epigenetically different from a nerve cell because a skin cell needs different active genes than a nerve cell, even though both cells have identical genome sequences (as will every other cell in our body).
Although many epigenetic modifications are intrinsic - naturally occurring as part of our development and our biology - other epigenetic changes are caused by our environment. Unfortunately, not all of them are good for our health. Environmentally caused epigenetic modifications are called extrinsic. Like the intrinsic epigenome, these extrinsic modifications cause changes in gene expression and regulation. Some of these extrinsic epigenetic changes even have negative effects, such as uncontrolled cell growth in cancer.
Because of this relationship, scientists hope that understanding epigenetic modifications can unlock the mystery behind some cancers. In this case, the scientists at Johns Hopkins were curious if there was a widespread epigenetic modification that caused skin cancer. And, if so, they wondered whether sun exposure and aging were responsible for these epigenetic modifications. They were particularly interested in whether DNA methylation - an epigenetic modification where a methyl group (a carbon atom and three hydrogen atoms) bonds to one of the As, Cs, Ts, or Gs - is affected by age and sun exposure.
Therefore, the scientists conducted DNA methylation analysis on samples from ten individuals under 35 and ten individuals over 60. Two samples were taken from each participant: one from a sun-exposed location (for example, the face) and one sun-protected (for example, the inner arm). The researchers wanted to compare these sun-exposed and sun-protected samples to each other in the same individual. However, they were also interested in comparing the samples between younger and older individuals to see if there were age-related differences in the samples. Finally, they also compared these results to similar data from samples of squamous cell carcinoma, a common type of skin cancer. These many samples allowed for ample comparison and analysis.
The scientists discovered a relationship between DNA methylation, aging and sun exposure. There was much less DNA methylation (hypomethylation) in the sun-exposed skin of older individuals, particularly in regions of the genome known to be important in human development and disease. A similar level of DNA hypomethylation was seen in the squamous cell carcinoma samples. This similarity hints that DNA hypomethylation may be related to skin cancer.
However, the scientists did not find the same level of DNA hypomethylation in the sun-protected skin of older individuals or in the sun-exposed skin of younger individuals. These results suggest there is a particular connection between aging and sun exposure. Together, sun exposure and aging have a greater effect on the epigenome than sun exposure alone or aging alone.
The scientists were also able to determine a difference in the effect of sun exposure on different types of skin cells. When analyzing the skin samples from each individual, the scientists separated the samples into epidermis (the outer-most layer of skin) and dermis (an inner layer). Intuitively, we may expect that the outer layer of our skin would be more affected by the sun, and indeed, the scientists found this to be true. By studying the DNA methylation in the epidermis, the scientists were able to cluster the samples based on age and sun exposure. However, the dermis did not cluster in the same way, suggesting that the DNA methylation in the dermis is less affected by chronic sun exposure and age.
These insights have strengthened our understanding about the relationship between sun exposure, aging and skin cancer, as well as illuminating some of the effects of sun exposure on the epigenome. With these topical insights in mind, we can welcome the summer and have fun in the sun with a renewed appreciation for genomic research, sun protection and the need for sunscreen.
Vandiver AR, Irizarry RA, Hansen KD, et al. Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin. Genome Biology, 16(1):80. 2015. [Full Text]
Last Updated: June 2, 2015