2016 Arte Poster Competition First Place Winner: Circadian Rhythm and UV-Induced Skin Damage: An In Vivo Study
September 2016 | Volume 15 | Issue 9 | Features | 1124 | Copyright © September 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.
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,
