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In this study, a comprehensive characterization of xenobiotic metabolizing enzymes (XMEs) based on gene expression and enzyme functionality was made in a reconstructed skin epidermal model derived from the outer root sheath (ORS) of hair follicles (ORS-RHE). The ORS-RHE model XME gene profile was consistent with native human skin. Cytochromes P450 (CYPs) consistently reported to be detected in native human skin were also present at the gene level in the ORS-RHE model. The highest Phase I XME gene expression levels were observed for alcohol/aldehyde dehydrogenases and (carboxyl) esterases. The model was responsive to the CYP inducers, 3-methylcholanthrene (3-MC) and β-naphthoflavone (βNF) after topical and systemic applications, evident at the gene and enzyme activity level. Phase II XME levels were generally higher than those of Phase I XMEs, the highest levels were GSTs and transferases, including NAT1. The presence of functional CYPs, UGTs and SULTs was confirmed by incubating the models with 7-ethoxycoumarin, testosterone, benzo(a)pyrene and 3-MC, all of which were rapidly metabolized within 24h after topical application. The extent of metabolism was dependent on saturable and non-saturable metabolism by the XMEs and on the residence time within the model. In conclusion, the ORS-RHE model expresses a number of Phase I and II XMEs, some of which may be induced by AhR ligands. Functional XME activities were also demonstrated using systemic or topical application routes, supporting their use in cutaneous metabolism studies. Such a reproducible model will be of interest when evaluating the cutaneous metabolism and potential toxicity of innovative dermo-cosmetic ingredients.

The proportion of adults over 60 years of age is rapidly increasing and is estimated to reach approximately one-sixth of the global population by 2030. An ageing population is a real challenge for healthcare resources, including dermatologists and geriatricians, as age-related changes in skin integrity and barrier function make older adults more susceptible to developing skin pathologies such as pruritus, dermatitis and infections. Fragile skin arises from several interlinked causes, including age-related changes in skin barrier integrity, previous and current lifestyle choices, skin pathologies and medical interventions. Dermo-cosmetics can play a key role in enhancing skin care regimens and preventing pathologies in this age group. In vitro studies, clinical, and in-daily clinical practice studies of dermo-cosmetics have shown them to be effective in many skin conditions in older adults, like xerosis and pruritus. Incontinence-associated dermatitis (IAD), a common condition arising from contact with irritants such as urine and faeces which can significantly impact the quality of life of sufferers, can also be improved with a barrier cream in incontinent patients aged 70 years and older. This supplement focuses on the increased fragility of older skin, the development of common skin pathologies and the efficacy and tolerance of dermo-cosmetic products in older adults.JEADV alcohol consumption and sun exposure), medical procedures (e.g. surgery) and underlying pathologies can all contribute to the development of fragile skin. While not necessarily associated with disease per se, most patients presenting to dermatologists with fragile skin have pathological conditions such as acne, psoriasis and atopic dermatitis. 4 However, surveys reveal that a substantial proportion of people have perceived fragile skin, which, while not associated with disease, can cause redness, tightness, dryness and itching. 5,6 Globally, the incidence of fragile skin in adults has been estimated as 25-52%, across skin types and age groups. [4][5][6] In older adults, skin ageing makes individuals more vulnerable to develop fragile skin and associated pathologies resulting from impaired skin barrier function. The mechanisms and clinical relevance of age-related skin deterioration, the prevalence of skin disorders in older adults in Europe and recent in vitro, clinical and in-daily clinical practice studies of fragile skin in this age group will be covered in this supplement. Section 1: Fragile skin in older adultsIn addition to internal age-related changes in skin structure and functionality, physiological, circumstantial, pathological and iatrogenic fragile skin causes also contribute to the weakening of the epidermis and skin barrier in older adults. Physiological fragile skinOlder adults experience physiological fragile skin, as declines in the immune system function within the epidermis, and changes in epidermal and dermal structure contribute to a reduction in the effectiveness of the skin barrier function. 7 During adulthood, the skin ...

Background: Skin aging is characterized by slacking and loss of density, especially under ultraviolet (UV) radiation exposure. Objective: To investigate the beneficial effects of a combination containing bakuchiol (BK) and vanilla tahitensis extract (VTE) to prevent skin photoaging in vitro and to improve clinical outcomes for naturally aged skin. Materials and Methods: Human dermal fibroblasts were treated with active compounds, exposed to an acute dose of UVA and analyzed by confocal microscopy: actin network for morphology, interleukin-8 (IL-8) for inflammation and p16 for senescence. Human skin was used to evaluate chronic UVA-induced glycosaminoglycan (GAG) loss and to assess the benefit of topical application of a BK+VTE serum (Alcian blue staining). An open-label clinical trial was conducted in women applying the serum twice daily for 56 days (n=43). Skin remodeling was assessed by FaceScan ®. Firmness was evaluated through Dynaskin ® and clinical scoring. Skin radiance was also rated on standardized full-face photographs. Results: UVA induced a significant increase in IL-8 and p16 expression and marked morphological changes in fibroblasts. Treatment with BK or VTE alone prevented both actin network alteration and IL-8 upregulation. Interestingly, BK+VTE demonstrated synergistic protection against IL-8 and p16 overexpression. Serum application prevented GAG loss at the dermo-epidermal junction and increased dermal GAG in UVA-exposed skin explants. In the clinical trial, face ptosis was reduced by 11% on average for 26 responsive subjects and up to 23%. Depth of skin deformation was also reduced by 24% on average for 30 responsive subjects and up to 30%. This firming effect was confirmed by clinical scoring. Radiance was significantly improved by 29% on average for 33 responsive subjects. The serum demonstrated good tolerance/safety. Conclusion: BK+VTE combination demonstrated anti-aging efficacy and might provide a substantial benefit in the daily care of naturally aged skin in women, through their synergistic effect on inflammaging and senescence.

IntroductionNatural aging of skin tissues, the addition of the cumulative action of the time and radiation exposure result in skin atrophy, wrinkles and degeneration of the extracellular matrix (ECM). The aim of the study was to investigate the beneficial effect of a combination containing retinaldehyde (RAL), delta-tocopherol glucoside (delta-TC) and glycylglycine ole-amide (GGO) and of a dermocosmetic containing the combination.Materials and methodsThe protective effect of the combination was assessed through in vitro gene expression of ultraviolet (UV)-irradiated fibroblasts. A skin aging assay using UV light on ex vivo skin samples and a clinical study conducted in 36 women aged from 35 to 55 years with a minimum of level 4 to a maximum of level 6 on the crow’s feet photoscale assessed the antiaging effect of the dermocosmetic.ResultsWhen added to UV-irradiated fibroblasts, the combination substantially improved the ECM in activating the elastin fiber production (fibrillin 2, fibulin 1 and 5 and lysyl oxidase-like 2) as well as that of proteins involved in the cellular ECM interactions (integrin b1, paxillin and actin a2). An ex vivo photodamaged human skin model showed that the dermocosmetic formulation containing the combination of the active ingredients protected the elastic network against UV-induced alterations including both elastin and fibrillin-rich fibers in the dermis. A daily application of the dermocosmetic for 2 months on naturally aged skin resulted in a statistically significant improvement (p<0.05) of visible signs of aging comprising crow’s feet, wrinkles and periocular fine lines. Finally, the formulation was well tolerated.ConclusionThe dermocosmetic containing RAL, delta-TC and GGO provides a substantial benefit in the daily care of naturally aged skin in women aged 35–55 years.