拜尔斯道夫股份公司

Skin aging is driven by intrinsic and extrinsic factors. Epigenetic alterations are one primary hallmark of aging and powerful biomarkers of biological skin age. To investigate epigenetic skin aging mechanisms and their regulation as a skin longevity approach across diverse ethnicities and phototypes, we assessed epidermal methylomes from white, African, and Asian donors. We collected epidermis samples from 17 multi-ethnic donors with diverse phototypes using a newly established tape-stripping method followed by array-based DNA methylation profiling to investigate the robustness of DNA methylation clocks across diverse ethnic backgrounds. Additionally, we conducted a clinical study with 60 participants representing Fitzpatrick phototypes I–VI. Diverse clinical parameters and biological skin age of the volunteers were determined at baseline and after applying a serum containing the natural epigenetic inhibitor dihydromyricetin (DHM) for 8 weeks to investigate skin longevity effects across phototypes. Data analysis revealed that age-dependent DNA hypermethylation is conserved across populations and affects genes essential for keratinocyte vitality and longevity. A newly developed epidermal methylation clock accurately predicted biological age in multi-ethnic cohorts, confirming the robustness of epigenetic age estimation across phototypes. Topical application of a DHM-containing serum significantly reduced epidermal DNA methylation age. Epigenetic rejuvenation was associated with clinical improvements, including reduced skin roughness and wrinkle visibility and occupancy, and increased dermal echogenicity. Together, these findings establish that epigenetic aging signatures are conserved across ethnicities and that targeted modulation using a DHM-containing topical formulation can reverse biological skin age while improving structural and visible signs of aging. This work provides the clinical evidence supporting epigenetic rejuvenation as a viable strategy for skin longevity across diverse populations.

Under the European Cosmetic Regulation, safety assessments of cosmetics and their ingredients must be conducted without the use of animals. This regulatory requirement poses a number of challenges, as validated alternative methods are only available for some of the toxicological endpoints that are typically considered in standard human health risk assessments. Despite significant progress since the ban in 2013, particularly in the development of New Approach Methodologies (NAMs) for local and acute toxicity, and for mutagenicity/genotoxicity, there remains an urgent need for non-animal test methods to assess systemic toxicity, which often becomes evident after repeated or long-term exposure. Currently, no validated animal-free alternatives are available for assessing sub-acute, sub-chronic and chronic toxicity, carcinogenicity, developmental/reproductive toxicity, or for a major part of toxicokinetics. In response to these challenges, the Methodology Working Group of the Scientific Committee on Consumer Safety organised a dedicated workshop in December 2024 to discuss advances in the application of Next Generation Risk Assessment (NGRA) as a strategic animal-free approach for the safety assessment of cosmetic ingredients. The workshop focused on a number of important key issues for the practical application of NAMs and NGRA, their regulatory acceptance and identification of possible (partial) solutions to overcome existing limitations.

Melasma is a common and recurring disorder of hyperpigmentation, characterized by dark spots that are distributed on sun-exposed areas of the skin. Whereas studies on sun-induced skin pigmentation have concentrated on implications of ultraviolet (UV) radiation, the effect of visible light (VIS) was long considered negligible. Optically opaque, tinted face care products have shown to prevent darkening of melasma spots, leading to the hypothesis that VIS plays a role in hyperpigmentation. Here, we analyzed the effects of VIS on melasma, and investigated how skin reacts to the exposure of UV and VIS irradiation, both separately and combined. Furthermore, we examined the impact of daily treatment with the tyrosinase inhibitor isobutylamido thiazolyl resorcinol (Thiamidol) on repetitive VIS irradiation. We show that melasma lesions respond more strongly to VIS than perilesional skin and were more conspicuous after irradiation. Also, in healthy skin, VIS alone induced immediate pigment darkening and delayed tanning. However, compared to vehicle treatment, the tyrosinase inhibitor Thiamidol significantly reduced the VIS-induced darkening in healthy skin.

The human facial skin microbiome is a complex and dynamic ecosystem that plays a central role in maintaining skin health, immune regulation, and preventing dermatological skin conditions. Cutibacterium acnes (C. acnes) and Staphylococcus epidermidis (S. epidermidis) are the most prominent bacterial species, with shifts in their relative abundance correlating with skin site, age, skin site, and health status. Exploring the facial microbiome offers exciting opportunities, though it requires careful methodological consideration. Sampling techniques vary in invasiveness and depth, which can influence the accuracy and reproducibility of microbiome profiles. While traditional cultivation methods provide valuable insights, they often miss nonculturable microbes, limiting the view of microbial diversity. Molecular approaches such as amplicon sequencing and metagenomics enable a more comprehensive understanding of microbial communities, even though they currently cannot distinguish between viable and nonviable microbes. Addressing these challenges will help unlock the full potential of facial microbiome research. A balanced facial skin microbiome is associated with healthy skin, whereas a dysbiosis of C. acnes and S. epidermidis is commonly observed in acne-prone skin and more pronounced clinically manifest acne. A comprehensive understanding of the diversity and distribution of C. acnes phylotypes, as well as distinct lineages of S. epidermidis associated with skin disorders, is crucial for developing targeted, microbiome-based cosmetic and medical treatments. Emerging strategies aim to restore microbial balance by leveraging the skin’s native microbiota, including probiotic approaches. These strategies represent a promising yet still emerging approach, as current clinical evidence remains limited and further well-controlled studies are required, although they may offer benefits by enhancing microbial diversity and supporting skin barrier function.

Single-cell and spatial transcriptomics have transformed the ability to chart human tissue organization at high resolution, enabling the construction of reference atlases and robust gene marker identification. The skin, as the largest human organ, lacks a comprehensive integrated atlas, particularly for the pilosebaceous unit, a key epithelial structure involved in homeostasis and disease. We present a framework for a scalable healthy Human Skin Cell Atlas that systematically integrates 34 publicly available single-cell RNA sequencing datasets comprising 818,951 cells, with harmonized metadata and standardized cell type nomenclature. In addition, we generated a new high-resolution Visium HD spatial transcriptomics dataset, demonstrating the benefits of integrating spatial information with single-cell data and enabling the mapping of hair follicle compartments and the identification of critical signaling hubs. The integrated atlas revealed cell types not detectable in individual datasets, including Merkel cells, and refined the classification of pilosebaceous unit subtypes. Importantly, the Human Skin Cell Atlas enables the rapid annotation of new datasets and the assessment of mapping uncertainties, facilitating the discovery of rare or disease-specific cell types. This resource provides a comprehensive and expandable reference for healthy human skin and illustrates the value of combining single-cell and spatial data for studies of tissue organization, disease mechanisms, and regenerative medicine.