Skin is a key organ maintaining internal homeostasis by performing many functions such as water loss prevention, body temperature regulation and protection from noxious substance absorption, microorganism intrusion and physical trauma. Skin ageing has been well studied and it is well known that physiological changes in the elderly result in higher skin fragility favouring the onset of skin diseases. For example, prolonged and/or high‐intensity pressure may suppress local blood flow more easily, disturbing cell metabolism and inducing pressure injury (PI) formation. Pressure injuries (PIs) represent a significant problem worldwide and their prevalence remains too high. A higher PI prevalence is correlated with an elderly population. Newborn skin evolution has been less studied, but some data also report a higher PI prevalence in this population compared to older children, and several authors also consider this skin as physiologically fragile. In this review, we compare the characteristics of newborn and elderly skin in order to determine common features that may explain their fragility, especially regarding PI risk. We show that, despite differences in appearance, they share many common features leading to higher fragility to shear and pressure forces, not only at the structural level but also at the cellular and molecular level and in terms of physiology. Both newborn and elderly skin have: (i) a thinner epidermis; (ii) a thinner dermis containing a less‐resistant collagen network, a higher collagen III:collagen I ratio and less elastin; (iii) a flatter dermal–epidermal junction (DEJ) with lower anchoring systems; and (iv) a thinner hypodermis, resulting in lower mechanical resistance to skin damage when pressure or shear forces are applied. At the molecular level, reduced expression of transforming growth factor β (TGFβ) and its receptor TGFβ receptor II (TβRII) is involved in the decreased production and/or increased degradation of various dermal extracellular matrix (ECM) components. Epidermal fragility also involves a higher skin pH which decreases the activity of key enzymes inducing ceramide deficiency and reduced barrier protection. This seems to be correlated with higher PI prevalence in some situations. Some data also suggest that stratum corneum (SC) dryness, which may disturb cell metabolism, also increases the risk of PI formation. Besides this structural fragility, several skin functions are also less efficient. Low applied pressures induce skin vessel vasodilation via a mechanism called pressure‐induced vasodilation (PIV). Individuals lacking a normal PIV response show an early decrease in cutaneous blood flow in response to the application of very low pressures, reflecting vascular fragility of the skin that increases the risk of ulceration. Due to changes in endothelial function, skin PIV ability decreases during skin ageing, putting it at higher risk of PI formation. In newborns, some data lead us to hypothesize that the nitric oxide (NO) pathway is not fully functional at birth, which m...

Human skin homeostasis requires sebum production regulation.Sebum is produced by sebaceous glands (SG) located in skin dermis and often associated with a hair follicle forming a pilo-sebaceous unit. 1 Various sebum functions such as skin protection against dehydration 2 or antibacterial and anti-oxidant properties 3,4 are well known. In rodents, a role in thermoregulation and resistance against UVB-induced apoptosis 5-7 has also been shown. However, those effects remain unclear for human skin 8 and, even if a real correlation between SG morphology and hair loss has also been shown, 9 sebum effect on human hair follicle integrity remains unclear. AbstractObjectives: Sebaceous glands maintain skin homeostasis by producing sebum. Low production can induce hair loss and fragile skin. Overproduction provokes seborrhoea and may lead to acne and inflammatory events. To better study sebaceous gland maintenance, sebocyte maturation, lipid production and ageing or inflammatory processes, we developed innovative 3D ex vivo models for human sebaceous glands. Materials and Methods: Culture conditions and analytical methods optimized on sebocyte monolayers were validated on extracted sebaceous glands and allowed the development of two 3D models: (a) "air-liquid" interface and (b) human fibronectincoated "sandwich" method. Lipid production was assessed with microscopy, fluorometry or flow cytometry analysis after Nile Red staining. Specific lipids (particularly squalene and peroxidized squalene) were measured by Gas or liquid Chromatography and Mass spectrometry.Results: This study allowed us to select appropriate conditions and design Seb4Gln culture medium inducing sebocyte proliferation and neutral lipid production. The "air-liquid" model was appropriate to induce sebocyte isolation. The "sandwich" model enabled sebaceous gland maintenance up to 42 days. A treatment with Insulin Growth Factor-1 allowed validation of the model as we succeeded in mimicking dynamic lipid overproduction. Conclusion:Functional sebocyte maturation and physiological maintenance were preserved up to 6 weeks in our models. Associated with functional assays, they provide a powerful platform to mimic physiological skin lipid metabolism and to screen for active ingredients modulating sebum production.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Green© CTI Biotech © CTI Biotech © CTI Biotech © CTI Biotech © CTI Biotech © BCS-BASF © BCS-BASF MC5R Muc-1 SG SG SG SG © CTI Biotech SG DAPI (blue) K7 (green) K5 (red) © CTI Biotech DAPI (blue) K7 (green) Muc1 (red) DAPI (blue) K7 (green) Muc1 (red) © CTI Biotech DAPI (blue) K7 (green) PPARγ (red) DAPI (blue) K7 (green) K5 (red)

The cover image is based on the Original Article Development of new 3D human ex vivo models to study sebaceous gland lipid metabolism and modulations by Anne‐France de Bengy et al., https://doi.org/10.1111/cpr.12524.

Many changes characterize skin aging, and the resulting dysfunctions still constitute a real challenge for our society. The aim of this study was to compare the skin aging of two rat strains, Wistar and Brown Norway (BN), considered as “poorly aging” and “healthy aging” models, respectively, and to assess the effect of alpha-lipoic acid (LPA), especially on skin microcirculation. To this purpose, various skin characteristics were studied at 6, 12, and 24 months and compared to the results of LPA treatment performed at 12 or 24 months. Skin aging occurred in both strains, but we showed an early occurrence of different age-related disorders in the Wistar strain compared to BN strain, especially regarding weight gain, glycemia dysregulation, basal skin perfusion, endothelial function, and skin resistance to low pressure. LPA treatment tended to improve skin resistance to low pressure in BN but not in Wistar despite the improvement of basal skin perfusion, endothelial function, and skin sensory sensitivity. Overall, this study confirmed the healthier aging of BN compared to Wistar strain and the positive effect of LPA on both general state and skin microcirculation.