2016 Arte Poster Competition First Place Winner: Circadian Rhythm and UV-Induced Skin Damage: An In Vivo Study openaccess articles

September 2016 | Volume 15 | Issue 9 | Feature | 1124 | Copyright © 2016

Linna Guan BS,a,* Amanda Suggs MD,a,* Sayeeda Ahsanuddin BS,a Madeline Tarrillion DO,a Jacqueline Selph MD,a Minh Lam PhD,a and Elma Baron MDa,b,c

aDepartment of Dermatology, Case Skin Diseases Research Center, bCase Western Reserve University/University Hospitals Case Medical Center, cLouis-Stokes VA Medical Center, Cleveland, OH *These authors contributed equally to the work.

Abstract

Exposure of the skin to ultraviolet (UV) irradiation causes many detrimental effects through mechanisms related to oxidative stress and DNA damage. Excessive oxidative stress can cause apoptosis and cellular dysfunction of epidermal cells leading to cellular senescence and connective tissue degradation. Direct and indirect damage to DNA predisposes the skin to cancer formation. Chronic UV exposure also leads to skin aging manifested as wrinkling, loss of skin tone, and decreased resilience. Fortunately, human skin has several natural mechanisms for combating UV-induced damage. The mechanisms operate on a diurnal rhythm, a cycle that repeats approximately every 24 hours. It is known that the circadian rhythm is involved in many skin physiologic processes, including water regulation and epidermal stem cell function. This study evaluated whether UV damage and the skin’s natural mechanisms of inflammation and repair are also affected by circadian rhythm. We looked at UV-induced erythema on seven human subjects irradiated with simulated solar radiation in the morning (at 08:00 h) versus in the afternoon (at 16:00 h). Our data suggest that the same dose of UV radiation induces significantly more inflammation in the morning than in the afternoon. Changes in protein expression relevant to DNA damage, such as xeroderma pigmentosum, complementation group A (XPA), and cyclobutane pyrimidine dimers (CPD) from skin biopsies correlated with our clinical results. Both XPA and CPD levels were higher after the morning UV exposure compared with the afternoon exposure.

J Drugs Dermatol. 2016;15(9):1124-1130.

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INTRODUCTION

The human body and its functions have a natural rhythm controlled by a region in the anterior hypothalamus known as the suprachiasmatic nucleus. This region modulates many physiological processes in a pattern that follows a 24-hour cycle, known as the circadian rhythm.1 Circadian rhythm is influenced by light and dark cycles and regulates hormone levels, body temperature, and sleep.2,3,4 This central clock also relays signals to peripheral organs and plays an integral role in skin function.5,6 One of the main functions of the skin is to maintain homeostasis by acting as a barrier against water loss. The circadian rhythm affects the skin’s role in water homeostasis by regulating the expression of aquaporin 3 in the epidermal stratum basalis for the modulation of water content and trans-epidermal water loss.7 In addition, epidermal stem cells also display temporal oscillations in a circadian manner.8 The stem cells’ ability to undergo mitosis also assists in skin homeostasis through proliferation, differentiation, and response to UV damage. Furthermore, it has been reported that the skin displays time-dependent variations in temperature, pH, and barrier function.9

A recent mouse study demonstrated that UV-induced erythema in mouse skin was also affected by circadian rhythm.10 It was shown that under the same UV conditions, mice irradiated in the AM showed significantly elevated erythemal response compared with those mice irradiated in the PM.10 It is already established that ultraviolet radiation (UVR) causes many adverse effects on the skin from photoaging, increased susceptibility to skin cancer,

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