Time-Restricted Feeding Shifts the Skin Circadian Clock and Alters UVB-Induced DNA Damage

Hong Wang,Elyse Van Spyk,Qiang Liu,Mikhail Geyfman,Michael L Salmans,Vivek Kumar,Alexander Ihler,Ning Li,Joseph S Takahashi,Bogi Andersen

doi:10.1016/j.celrep.2017.07.022

Abstract

The epidermis is a highly regenerative barrier protecting organisms from environmental insults, including UV radiation, the main cause of skin cancer and skin aging. Here, we show that time-restricted feeding (RF) shifts the phase and alters the amplitude of the skin circadian clock and affects the expression of approximately 10% of the skin transcriptome. Furthermore, a large number of skin-expressed genes are acutely regulated by food intake. Although the circadian clock is required for daily rhythms in DNA synthesis in epidermal progenitor cells, RF-induced shifts in clock phase do not alter the phase of DNA synthesis. However, RF alters both diurnal sensitivity to UVB-induced DNA damage and expression of the key DNA repair gene, Xpa. Together, our findings indicate regulation of skin function by time of feeding and emphasize a link between circadian rhythm, food intake, and skin health.

Highlights

Acting as a strong barrier to physical, chemical, and pathogenic insults from the exterior, and to water loss from the interior, the epidermis, the outermost layer of the skin, is a stratified epithelium
restricted feeding (RF) Entrains the Skin Circadian Clock in a Manner Distinct from that of the Liver To determine whether RF can shift the phase of the skin circadian clock, we administered five different feeding schedules (Figure 1A)
The early nighttime (EN) feeding group had access to food starting at ZT12

Summary

Introduction

Acting as a strong barrier to physical, chemical, and pathogenic insults from the exterior, and to water loss from the interior, the epidermis, the outermost layer of the skin, is a stratified epithelium. Recent work has unearthed an important role for the circadian clock in regulating skin function (Plikus et al, 2015) This raises the intriguing possibility that signals that influence circadian clocks, such as the time of feeding, could act as a regulator of skin function; the clocks in some peripheral tissues, especially metabolic organs, including the liver, can be entrained by time-restricted feeding (RF) (Damiola et al, 2000; Hara et al, 2001; Izumo et al, 2014; Kuroda et al, 2012; Stokkan et al, 2001). The central and peripheral clocks are transcription-translation feedback loops wherein the heterodimeric CLOCK/BMAL1 transcription complex activates a large number of genes These include PERs and CRYs that form heterodimers to inhibit CLOCK/BMAL1 activity, establishing an oscillating transcriptional output with 24 hr periodicity (Dibner et al, 2010; Lowrey and Takahashi, 2011; Mohawk et al, 2012).

Results

Discussion

Conclusion