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Molecular Mechanisms for Skin Protection and Aging
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Molecular Mechanisms for Skin Protection and Aging

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 4644

Special Issue Editors

Dr. Wonchul Lim

E-Mail Website
Guest Editor
Department of Food Science & Biotechnology, Sejong University, Seoul 05006, Republic of Korea
Interests: skin aging; anti-skin aging; molecular biology; inner beauty; natural product; ultraviolet; particulate matter; skin wrinkle formation; skin hydration; skin hyperpigmentation; epidermis; dermis; keratinocyte; fibroblast; melanocyte; langerhans cell; merkel cell; nutrigenomics; proteomics; phosphoproteomics
Dr. Tae-Gyu Lim

E-Mail Website
Guest Editor
Department of Food Science & Biotechnology, Sejong University, Seoul 05006, Republic of Korea
Interests: skin aging; molecular biology; inner beauty; natural product; ultraviolet; particulate matter; microplastics; anti-obesity; hair promoting; cancer; skin wrinkle formation; skin hydration; skin whitening; skin hyperpigmentation; epidermis; dermis; nutrigenomics; proteomics; phosphoproteomics; metabolomics; transcriptome; multi-omics

Special Issue Information

Dear Colleagues,

The skin, as the largest organ on the body's surface, is crucial for protecting against external factors such as ultraviolet radiation, smoking, extreme temperatures, and other pollutants. Intrinsic and extrinsic types of skin aging contribute to common signs like wrinkle formation, dehydration, hyperkeratinization, and hyperpigmentation. Advanced studies with cell lines, primary cells, and animal models can use techniques like qRT-PCR, Western blotting, nutrigenomics, proteomics, phosphoproteomics, and lipidomics to uncover the roles of new biomarkers or anti-aging agents.

This Special Issue aims to explore the complex mechanisms of skin aging and discover innovative approaches to mitigate its effects. We invite research focused on elucidating novel mechanisms responsible for skin aging, offering new insights into the biological processes involved. We highly encourage studies on the discovery and investigation of new agents with anti-aging properties, particularly focusing on their mechanisms of action. By fostering a deeper understanding of skin aging and identifying effective interventions, this Special Issue aspires to advance the field of dermatological science and contribute to the development of more effective skincare solutions.

The scope of this Special Issue includes, but is not limited to, the following topics:

  • New insights into the biological processes involved in skin aging;
  • The discovery and investigation of novel agents with anti-skin aging effects;
  • Theoretical results emphasizing the mechanisms of anti-aging agents;
  • The discovery of anti-aging agents using computational biology;
  • The development of innovative approaches to mitigate the effects of skin aging.

Dr. Wonchul Lim
Dr. Tae-Gyu Lim
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • skin photo-aging
  • skin inflammation
  • molecular biology
  • inner beauty
  • natural product
  • skin microbiome
  • skin wrinkle formation
  • skin dehydration
  • skin pigmentation

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (4 papers)

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Research

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15 pages, 2090 KiB  
Article
Assessment of the Curative Anti-Glycation Properties of a Novel Injectable Formulation Combining Dual-Weight Hyaluronic Acid (Low- and Mid/High-Molecular Weight) with Trehalose on Human Skin Ex Vivo
by Robert Chmielewski, Agata Lebiedowska and Wioletta Barańska-Rybak
Int. J. Mol. Sci. 2025, 26(10), 4747; https://doi.org/10.3390/ijms26104747 - 15 May 2025
Viewed by 196
Abstract
Glycation influences skin aging through non-enzymatic reactions between reducing sugars and proteins, forming advanced glycation end-products (AGEs) that accelerate skin deterioration. This study evaluates the curative anti-glycation effects of an injectable formulation combining dual-molecular-weight hyaluronic acid (low and mid/high) with trehalose in methylglyoxal-induced [...] Read more.
Glycation influences skin aging through non-enzymatic reactions between reducing sugars and proteins, forming advanced glycation end-products (AGEs) that accelerate skin deterioration. This study evaluates the curative anti-glycation effects of an injectable formulation combining dual-molecular-weight hyaluronic acid (low and mid/high) with trehalose in methylglyoxal-induced glycation in human skin explants. Thirty-six human skin explants were allocated across five experimental groups in a 12-day study. Glycation was induced using methylglyoxal (500 μM) on days 1 and 4, followed by curative product administration on day 5. CML (Nε-(carboxymethyl)lysine) immunohistochemistry was performed to assess glycation levels in the reticular dermis at days 6, 8, and 12, with quantitative analysis conducted through standardized image analysis. The formulation significantly reduced CML formation by 60% on day 6 compared to untreated controls (p < 0.001). Under methylglyoxal-induced glycation stress the product showed sustained curative effects, with CML reductions of 69% on day 6 (p = 0.008), 68% on day 8 (p = 0.012), and 61% on day 12 (p = 0.033) compared to methylglyoxal treatment alone. Cell viability remained unaffected throughout the study period across all experimental conditions. The tested injectable formulation exhibits significant and sustained curative anti-glycation properties in human skin explants for 12 days, effectively counteracting methylglyoxal-induced glycation damage without affecting cell viability. These findings advance anti-aging skin interventions, offering a novel approach to address glycation-induced skin damage with potential applications in clinical dermatology and aesthetic medicine. Full article
(This article belongs to the Special Issue Molecular Mechanisms for Skin Protection and Aging)
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16 pages, 2701 KiB  
Article
Evaluation of the Anti-Glycation Protective Effect of an Injectable Product Based on a Combination of Two Different Ranges of Molecular Weights of Hyaluronic Acid and Trehalose on Human Skin Explants
by Robert Chmielewski, Agata Lebiedowska and Wioletta Barańska-Rybak
Int. J. Mol. Sci. 2025, 26(7), 3217; https://doi.org/10.3390/ijms26073217 - 30 Mar 2025
Viewed by 496
Abstract
Skin aging is significantly influenced by glycation processes, leading to the formation of Advanced Glycation End-products (AGEs) that compromise dermal structure and function. This study evaluated the protective effects of a novel injectable product based on a combination of two different ranges of [...] Read more.
Skin aging is significantly influenced by glycation processes, leading to the formation of Advanced Glycation End-products (AGEs) that compromise dermal structure and function. This study evaluated the protective effects of a novel injectable product based on a combination of two different ranges of Molecular Weights of Hyaluronic Acid (MWHA: LMWHA-Low MWHA, MMWHA-Mid MWHA, and HMWHA-High MWHA) and trehalose against glycation in human skin explants. Using human skin explants with methylglyoxal-induced glycation stress, we assessed the product’s impact on carboxymethyllysine (CML) formation and cell viability in the reticular dermis. The product was administered prophylactically one day before methylglyoxal exposure, and samples were analyzed after six days. Results demonstrated that the product significantly reduced CML formation by 45% (p < 0.01) compared to untreated controls under baseline conditions and maintained a 30% reduction (p < 0.05) in CML formation under methylglyoxal-induced stress. Importantly, the product preserved cell viability throughout the experimental period and maintained CML levels comparable to physiological baseline despite glycation stress. These findings suggest that the synergistic action of hyaluronic acid and trehalose provides effective protection against both baseline and induced glycation in human skin, indicating potential applications in preventing glycation-related skin aging. Full article
(This article belongs to the Special Issue Molecular Mechanisms for Skin Protection and Aging)
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23 pages, 6086 KiB  
Article
Inflammatory Transformation of Skin Basal Cells as a Key Driver of Cutaneous Aging
by Shupeng Liu, Sheng Lu, Zhiping Pang, Jiacheng Li, Meijuan Zhou, Zhenhua Ding and Zhijun Feng
Int. J. Mol. Sci. 2025, 26(6), 2617; https://doi.org/10.3390/ijms26062617 - 14 Mar 2025
Viewed by 641
Abstract
This study comprehensively investigated keratinocyte subpopulation heterogeneity and developmental trajectories during skin aging using single-cell sequencing, transcriptomics, and facial aging-related genome-wide association studies (GWAS) data. We identified three major subpopulations: basal cells (BCs), spinous cells (SCs), and IFI27+ keratinocytes. Single-cell pseudotime analysis [...] Read more.
This study comprehensively investigated keratinocyte subpopulation heterogeneity and developmental trajectories during skin aging using single-cell sequencing, transcriptomics, and facial aging-related genome-wide association studies (GWAS) data. We identified three major subpopulations: basal cells (BCs), spinous cells (SCs), and IFI27+ keratinocytes. Single-cell pseudotime analysis revealed that basal cells can differentiate along two distinct paths: toward spinous differentiation or the inflammatory state. With aging, the proportion of IFI27+ cells significantly increased, displaying more active inflammatory and immunomodulatory signals. Through cell–cell communication analysis, we found that the signaling pathways, including NOTCH, PTPR, and PERIOSTIN, exhibited distinct characteristics along different branches. Integration of the GWAS data revealed significant loci on chromosomes 2, 3, 6, and 9 that were spatially correlated with key biological pathways (including antigen processing, oxidative stress, and apoptosis). These findings reveal the complex cellular and molecular mechanisms underlying skin aging, offering potential targets for novel diagnostic approaches and therapeutic interventions. Full article
(This article belongs to the Special Issue Molecular Mechanisms for Skin Protection and Aging)
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Review

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23 pages, 1115 KiB  
Review
Effectiveness of Extracellular Vesicle Application in Skin Aging Treatment and Regeneration: Do We Have Enough Evidence from Clinical Trials?
by Anna Domaszewska-Szostek, Marta Krzyżanowska, Agnieszka Polak and Monika Puzianowska-Kuźnicka
Int. J. Mol. Sci. 2025, 26(5), 2354; https://doi.org/10.3390/ijms26052354 - 6 Mar 2025
Viewed by 2423
Abstract
In recent years, there has been a dynamic development in therapies utilizing extracellular vesicles (EVs) including exosomes. Therefore, we have conducted an analysis of the scientific literature to verify the current state of knowledge about these therapies. A total of 12 clinical studies [...] Read more.
In recent years, there has been a dynamic development in therapies utilizing extracellular vesicles (EVs) including exosomes. Therefore, we have conducted an analysis of the scientific literature to verify the current state of knowledge about these therapies. A total of 12 clinical studies were analyzed, covering the use of EVs in treating skin aging, acne scars, alopecia, and wound healing. The results indicate that EVs and exosomes hold potential in regenerative skin therapies, offering innovative and non-invasive therapeutic approaches. At the same time, significant challenges related to the standardization of their production and the lack of large-scale randomized studies were identified. Thus, we also evaluated the investigated clinical trials in regard to the MISEV (Minimal Information for Studies of Extracellular Vesicles) criteria. This review provides a comprehensive overview of the contemporary applications of EVs in skin therapy and regenerative medicine, highlighting directions for further research. Full article
(This article belongs to the Special Issue Molecular Mechanisms for Skin Protection and Aging)
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