The circadian control of skin and cutaneous photodamage

Abstract

Biologically, light including ultraviolet (UV) radiation is vital for life. However, UV exposure does not come without risk, as it is a major factor in the development of skin cancer. Natural protections against UV damage may have been affected by lifestyle changes over the past century, including changes in our sun exposure due to working environments, and the use of sunscreens. In addition, extended "day time" through the use of artificial light may contribute to the disruption of our circadian rhythms; the daily cycles of changes in critical bio-factors including gene expression. Circadian disruption has been implicated in many health conditions, including cardiovascular, metabolic and psychiatric diseases, as well as many cancers. Interestingly, the pineal hormone melatonin plays a role in both circadian regulation as well as protection from UV skin damage, and is therefore an important factor to consider when studying the impact of UV light. This review discusses the beneficial and deleterious effects of solar exposure, including UV skin damage, Vitamin D production, circadian rhythm disruption and the impact of melatonin. Understanding these benefits and risks is critical for the development of protective strategies against solar radiation.

Figure 1. The Circadian Clock Network

BMAL1 and CLOCK proteins form a heterodimer in the nucleus followed by binding to the E-Box region in the promoter of their target genes, thereby initiating transcription. Two families of target genes, the Periods (PER) and Cryptochromes (CRY), then act in a negative feedback loop by forming a heterodimer, translocating to the nucleus, and interfering with BMAL1/CLOCK-induced transcription. The acetylation state of BMAL1, which is altered by CLOCK histone acetyltransferase and SIRT1 histone deacetylase activity, plays a large role in the regulation of this system.

Figure 2. Light, Circadian Rhythms, and Melatonin

1) UV or visible light from the sun is sensed by the retina, which signals the suprachiasmatic nucleus (SCN) region of the brain, enabling entrainment of circadian rhythms throughout the body. 2) UV light induces skin damage. Both Melatonin and Vitamin D₃ have protective effects against this damage, through the inhibition of reactive oxygen species (ROS) formation as well as other mechanisms. 3) UVB light exposure can cause disruption of the circadian rhythms in normal skin, but also has the protective effect of producing Vitamin D₃. 4) In addition to its protective effects against UVB skin damage, melatonin also plays a role in the regulation of circadian rhythms, through its inhibition of the HDAC SIRT1.