The Influence of Circadian Rhythms on DNA Damage Repair in Skin Photoaging

Zhi Su 1,†, Qianhua Hu 1,†, Xiang Li 1 , Zirun Wang 1 and Ying Xie 1,2,*

1 Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410081, China

2 Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, School of Medicine, Hunan Normal University, Changsha 410081, China

* Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

† These authors contributed equally to this work.

Abstract: Circadian rhythms, the internal timekeeping systems governing physiological processes, significantly influence skin health, particularly in response to ultraviolet radiation (UVR). Disruptions in circadian rhythms can exacerbate UVR-induced skin damage and increase the risk of skin aging and cancer. This review explores how circadian rhythms affect various aspects of skin physiology and pathology, with a special focus on DNA repair. Circadian regulation ensures optimal DNA repair following UVR-induced damage, reducing mutation accumulation, and enhancing genomic stability. The circadian control over cell proliferation and apoptosis further contributes to skin regeneration and response to UVR. Oxidative stress management is another critical area where circadian rhythms exert influence. Key circadian genes like brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) modulate the activity of antioxidant enzymes and signaling pathways to protect cells from oxidative stress. Circadian rhythms also affect inflammatory and immune responses by modulating the inflammatory response and the activity of Langerhans cells and other immune cells in the skin. In summary, circadian rhythms form a complex defense network that manages UVRinduced damage through the precise regulation of DNA damage repair, cell proliferation, apoptosis, inflammatory response, oxidative stress, and hormonal signaling. Understanding these mechanisms provides insights into developing targeted skin protection and improving skin cancer prevention.

Keywords: ultraviolet radiation; DNA damage repair; circadian rhythms; skin photoaging

Citation: Su, Z.; Hu, Q.; Li, X.; Wang, Z.; Xie, Y. The Influence of Circadian Rhythms on DNA Damage Repair in Skin Photoaging. Int. J. Mol. Sci. 2024, 25, 10926. https://doi.org/10.3390/ ijms252010926

Academic Editor: Ashis Basu

Received: 15 August 2024

Revised: 29 September 2024

Accepted: 8 October 2024

Published: 11 October 2024

Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)

Senomorphic activity of a combination of niacinamide and hyaluronic acid: correlation with clinical improvement of skin aging

Patrick Bogdanowicz 1,4*, Paul Bensadoun 2,4, Maïté Noizet 1 , Benoît Béganton 1 , Armony Philippe 1 , SandrineAlvarez‑Georges 1 , Gautier Doat 3 , AmélieTourette 1 , Sandrine Bessou‑Touya 1 , Jean‑Marc Lemaitre 2* & Hélène Duplan 1

1 R&D Pierre Fabre Dermo-Cosmétique & Personal Care, Toulouse, France.

2 INSERM IRMB UMR1183, Hôpital Saint Eloi, Université de Montpellier, Montpellier, France.

3 Laboratoires Dermatologiques Avène, Lavaur, France. 4These authors contributed equally: Patrick Bogdanowicz and Paul Bensadoun.

*email: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Intrinsic and extrinsic factors, including lifestyle and sun exposure, can contribute to cell senescence, which impairs skin homeostasis, that may in turn lead to skin aging. Senescent cells have a specifc secretome, called the senescence-associated secretory phenotype (SASP) that includes MMPs, CXCLs and S100A8/9. Reducing the SASP with senotherapeutics is a promising strategy to reduce skin aging. Here we evaluated the efect of a formula containing niacinamide and hyaluronic acid, which are known to limit senescence and skin aging. We conducted three diferent studies. (1) Ex vivo explants treated with the formula had more collagen and glycosaminoglycan. (2) In a clinical trial with forty-four women, two months of treatment improved fne lines, wrinkles, luminosity, smoothness, homogeneity, and plumpness. (3) In a third study on thirty women, we treated one arm for two months and took skin biopsies to study gene expression. 101 mRNAs and 13 miRNAs were diferentially expressed. We observed a likely senomorphic efect, as there was a decrease in many SASP genes including MMP12 and CXCL9 and a signifcant downregulation of autocrine signaling genes: S100A8 and S100A9. These pharmaco-clinical results are the frst to demonstrate the senomorphic properties of an efective anti-aging formula in skin.

Radiofrequency Treatment Attenuates Age-Related Changes in Dermal–Epidermal Junctions of Animal Skin

Kyung-A Byun 1,2,3,†, Hyoung Moon Kim 4,† , Seyeon Oh 3 , Sosorburam Batsukh 1,3, Kuk Hui Son 5,* and Kyunghee Byun 1,3,6,*

1 Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea

2 LIBON Inc., Incheon 22006, Republic of Korea

3 Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea

4 Maylin Anti-Aging Center Ilsan, Goyang 10391, Republic of Korea

5 Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Republic of Korea

6 Department of Health Sciences and Technology, Gachon Advanced Institute for Health & Sciences and Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea

* Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (K.H.S.); 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (K.B.); Tel.: +82-32-460-3666 (K.H.S.); +82-32-899-6511 (K.B.)

† These authors contributed equally to this work.

Abstract: The dermal–epidermal junction (DEJ) is essential for maintaining skin structural integrity and regulating cell survival and proliferation. Thus, DEJ rejuvenation is key for skin revitalization, particularly in age-related DEJ deterioration. Radiofrequency (RF) treatment, known for its ability to enhance collagen fiber production through thermal mechanisms and increase heat shock protein (HSP) expression, has emerged as a promising method for skin rejuvenation. Additionally, RF activates Piezo1, an ion channel implicated in macrophage polarization toward an M2 phenotype and enhanced TGF-β production. This study investigated the impact of RF treatment on HSP47 and HSP90 expression, known stimulators of DEJ protein expression. Furthermore, using in vitro and aged animal skin models, we assessed whether RF-induced Piezo1 activation and the subsequent M2 polarization could counter age-related DEJ changes. The RF treatment of H2O2 -induced senescent keratinocytes upregulated the expression of HSP47, HSP90, TGF-β, and DEJ proteins, including collagen XVII. Similarly, the RF treatment of senescent macrophages increased Piezo1 and CD206 (M2 marker) expression. Conditioned media from RF-treated senescent macrophages enhanced the expression of TGF-β and DEJ proteins, such as nidogen and collagen IV, in senescent fibroblasts. In aged animal skin, RF treatment increased the expression of HSP47, HSP90, Piezo1, markers associated with M2 polarization, IL-10, and TGF-β. Additionally, RF treatment enhanced DEJ protein expression. Moreover, RF reduced lamina densa replication, disrupted lesions, promoted hemidesmosome formation, and increased epidermal thickness. Overall, RF treatment effectively enhanced DEJ protein expression and mitigated age-related DEJ structural changes by increasing HSP levels and activating Piezo1.

Keywords: aged mice skin; bipolar; dermal–epidermal junction; heat shock protein; monopolar; Piezo1; radiofrequency

Citation: Byun, K.-A.; Kim, H.M.; Oh, S.; Batsukh, S.; Son, K.H.; Byun, K. Radiofrequency Treatment Attenuates Age-Related Changes in Dermal–Epidermal Junctions of Animal Skin. Int. J. Mol. Sci. 2024, 25, 5178. https://doi.org/10.3390/ ijms25105178

Academic Editor: Terrence Piva

Received: 16 April 2024

Revised: 3 May 2024

Accepted: 7 May 2024

Published: 9 May 2024

Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Epidermal stem cells: skin surveillance and clinical perspective

Xin Tang1†, Jiaqi Wang1†, Jiaoling Chen1†, Wanting Liu1 , Pei Qiao1 , Huiyi Quan1 , Zhiguo Li1 , Erle Dang1 , Gang Wang1* and Shuai Shao1*

Abstract

The skin epidermis is continually infuenced by a myriad of internal and external elements. At its basal layer reside epidermal stem cells, which fuels epidermal renovation and hair regeneration with powerful self-renewal ability, as well as keeping diverse signals that direct their activity under surveillance with quick response. The importance of epidermal stem cells in wound healing and immune-related skin conditions has been increasingly recognized, and their potential for clinical applications is attracting attention. In this review, we delve into recent advancements and the various physiological and psychological factors that govern distinct epidermal stem cell populations, including psychological stress, mechanical forces, chronic aging, and circadian rhythm, as well as providing an overview of current methodological approaches. Furthermore, we discuss the pathogenic role of epidermal stem cells in immune-related skin disorders and their potential clinical applications.

Keywords Epidermal stem cells, Aging, Wound healing, Immune-related skin disorders, Regeneration

† Xin Tang, Jiaqi Wang and Jiaoling Chen contributed equally to this work.

*Correspondence:

Gang Wang

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Shuai Shao

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1 Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shannxi, China

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modifed the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Cutting-edge skin ageing research on tissue stem cell

Received December 11, 2023; accepted February 20, 2024; published online February 26, 2024

Ryo Ichijo∗

Laboratory of Tissue Homeostasis, Department of Biosystems Science, Institute for Life and Medical Sciences, Kyoto University, 53 Shogoin

Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

∗Ryo Ichijo, Laboratory of Tissue Homeostasis, Department of Biosystems Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan. Tel.: +81-75-751-4016,

email: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

In developed economies, the growing number of older individuals is a pressing issue. As a result, research progress into ageing has emphasized the significance of staying healthy in one’s later years. Stem cells have a fundamental role to play in fostering diverse cell types and necessary processes for tissue repair and regeneration. Stem cells experience the effects of ageing over time, which is caused by their functional deterioration. Changes to stem cells, their niches and signals from other tissues they interact with are crucial factors in the ageing of stem cells. Progress in single-cell RNA sequencing (scRNA-seq) technology has greatly advanced stem cell research. This review examines the mechanisms of stem cell ageing, its impact on health and investigates the potential of stem cell therapy, with a special emphasis on the skin.

 Graphical Abstract

Keywords: ageing, homeostasis, regeneration, single cell RNA sequencing, stem cell.

Characterization of skin barrier defects using infrared spectroscopy in patients with atopic dermatitis

Samuel F. Williams , 1 Helen Wan,1 John Chittock , 1 Kirsty Brown,1 Andrew Wigley,1 Michael J. Cork 1,2,3 and Simon G. Danby 1

1 Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK

2 Sheffield Children’s NHS Foundation Trust, Sheffield Children’s Hospital, Western Bank, Sheffield, UK

3 Sheffield Teaching Hospitals NHS Foundation Trust, The Royal Hallamshire Hospital, Sheffield, UK Correspondence: Samuel F. Williams. Email: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Abstract

Background Atopic dermatitis (AD) is characterized by skin barrier defects that are often measured by biophysical tools that observe the functional properties of the stratum corneum (SC).

Objectives To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in the chemical composition of the SC in relation to AD severity.

Methods We conducted an observational cross-sectional cohort study where attenuated total reflection Fourier transform infrared (ATRFTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL), combined with tape stripping, in a cohort of 75 participants (55 patients with AD stratified by phenotypic severity and 20 healthy controls). Common FLG variant alleles were genotyped.

Results Reduced hydration, elevated TEWL and redness were all associated with greater AD severity. Spectral analysis showed a reduction in 1465 cm–1 (full width half maximum) and 1340 cm–1 peak areas, indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups, which correlated with clinical severity (lipid structure r=–0.59, carboxylate peak area r=–0.50).

Conclusions ATR-FTIR spectroscopy is a suitable tool for the characterization of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatment based on chemical structural deficiencies.

What is already known about this topic?

• The skin of patients with atopic dermatitis (AD) is characterized by atypical lipid levels and structure, diminished natural moisturizing factor (NMF) and filaggrin deficiency.

• As a result of these structural alterations, normal skin barrier function is reduced.
• Purpose-built probes or assays are typically used to monitor and quantify biochemical changes, such as pH, moisturization factors, hydration and transepidermal water loss (TEWL), on the epidermal surface as a result of the onset of dermatitis.

What does this study add?

• Characteristics from the mid-infrared spectra collected from participants’ skin provided molecular insight into the pathogenesis of AD.

• Lipid- and carboxylate-associated mid-infrared peaks were strongly associated with biophysical measurements, including skin hydration, NMF and TEWL.

• Peaks analysis also indicated a filaggrin deficiency, caused by genetic deposition or inflammatory action.
• Early detection of a genetic predisposition to AD would allow for preventative measures to be undertaken.

Accepted: 20 November 2023

© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。