Lieve Declercq

Topical application of green and white tea extracts provides protection from solar-simulated ultraviolet light in human skin

Background:  Tea polyphenols have been found to exert beneficial effects on the skin via their antioxidant properties.

Structural and functional differences in barrier properties of African American, Caucasian and East Asian skin

BACKGROUND Differences in structural and functional skin characteristics have been linked with ethnical background. But racial differences in skin have not been thoroughly investigated by objective methods and the data are often contradictory. OBJECTIVES This study was undertaken to compare skin barrier-related parameters of the stratum corneum on African American, Caucasian and East Asian skin by objective measurements. METHODS Baseline values of trans epidermal water loss were collected on the face. Consecutive stratum corneum D-squame tape strippings were collected on the panelists ventral forearm and face to evaluate skin barrier strength and cohesion. Stratum corneum ceramides, maturation, measured as the transglutaminase-mediated cross-linking of stratum corneum proteins, and stratum corneum trypsin like enzyme activity were measured on the D-squame tape strippings. RESULTS East Asian and to some extent Caucasian skin was characterized by low maturation and relatively weak skin barrier. African American skin was characterized by low ceramide levels and high protein cohesion in the uppermost layers of the stratum corneum. These data can be interpreted in terms of the high prevalence of xerosis in black skin and increased skin sensitivity in East Asian skin. CONCLUSION These results demonstrate that skin properties at the level of the stratum corneum vary considerably among these ethnic groups. This contributes to an improved understanding of physiological differences between these study populations.

Functional Interplay between Mitochondrial and Proteasome Activity in Skin Aging

According to the mitochondrial theory of aging, reactive oxygen species (ROS) derived primarily from mitochondria cause cumulative oxidative damage to various cellular molecules and thereby contribute to the aging process. On the other hand, a pivotal role of the proteasome, as a main proteolytic system implicated in the degradation of oxidized proteins during aging, is suggested. In this study, we analyzed mitochondrial function in dermal fibroblasts derived from biopsies obtained from healthy young, middle-aged, and old donors. We also determined proteasome activity in these cells, using a degron-destabilized green fluorescent protein (GFP)-based reporter protein. We found a significant decrease in mitochondrial membrane potential in samples from aged donors, accompanied by a significant increase in ROS levels. Respiratory activity was not significantly altered with donor age, probably reflecting genetic variation. Proteasome activity was significantly decreased in fibroblasts from middle-aged donors compared with young donors; fibroblasts derived from the oldest donors displayed a high heterogeneity in this assay. We also found intraindividual coregulation of mitochondrial and proteasomal activities in all human fibroblast strains tested, suggesting that both systems are interdependent. Accordingly, pharmacological inhibition of the proteasome led to decreased mitochondrial function, whereas inhibition of mitochondrial function in turn reduced proteasome activity.

Aging of Human Skin: Review of a Mechanistic Model and First Experimental Data

The physical, chemical, and biochemical factors that accelerate skin aging have been proposed to activate a self‐maintained micro‐inflammatory process, one of the expected end results of which is an imbalance in the turnover of macromolecules in the dermis. Surface peroxides are recognized as controllable factors of skin aging, and their accumulation is attributed to environmentally induced impairment of defense enzymes. Topical application of antioxidants decreases the rate at which skin elasticity and skin thickness are modified.

Glycation associated skin autofluorescence and skin elasticity are related to chronological age and body mass index of healthy subjects

Glycation is the non-enzymatic reaction between reducing sugars and proteins that leads to the formation of advanced glycation end products (AGEs). In vivo skin autofluorescence (lambda(ex)/lambda(em)=370/440 nm) was used as a non-invasive clinical tool to study skin AGE accumulation in healthy panellists. Using multiple linear regression analysis, it was shown that for panellists below the age of 40, glycation associated in vivo skin fluorescence intensity increased as a function of chronological age and body mass index (BMI). Above the age of 40, the fluorescence was associated to age but not to BMI, suggesting that the effect of age became dominant over BMI. Since the accumulation of AGEs is expected to affect the biomechanical properties of the skin, in vivo skin elasticity data were gathered on a second panel. It was found that skin elasticity depended on age and BMI in a similar fashion as to what we observed for the skin fluorescence data. It is hypothesised that skin AGE accumulation contributes to the loss of skin elasticity in aged and/or overweight people.

Adaptive response of the skin to UVB damage: role of the p53 protein.

Different adaptation mechanisms like heat shock response, cell cycle arrest and DNA repair, melanin pigmentation and thickening of the epidermis are present in the human skin to protect against the adverse effects of solar UV irradiation. When DNA damage is beyond repair, cells undergo apoptosis to prevent their replication. We discuss the current knowledge on these different adaptation mechanisms to UVB damage, the most energetic fraction of solar UV that reaches the skin. As p53 protein, the guardian of the genome, plays a key role in protective response to genotoxic damage, its role in this adaptive response of the skin to UV will be further discussed.

Arginase is overactive in psoriatic skin

Background  Psoriatic keratinocytes are poorly differentiated and hyperproliferative. Low concentrations of nitric oxide (NO) induce keratinocyte proliferation, while high concentrations induce differentiation. The NO‐producing enzyme inducible NO synthase is overexpressed in psoriatic skin, but so is arginase. The overexpressed arginase competes for arginine, the common substrate for both enzymes, and may reduce NO production.

Use of the synthetic superoxide dismutase/catalase mimetic EUK-134 to compensate for seasonal antioxidant deficiency by reducing pre-existing lipid peroxides at the human skin surface

The generation of reactive oxygen species (ROS) in UV‐exposed skin is believed to contribute to the photoaging process. The stratum corneum (SC) contains a variety of enzymatic and non‐enzymatic antioxidants to protect against various environmental sources of free radicals. We have previously shown a seasonal variation in SC catalase activity with strong deactivation in sun‐exposed skin in the summer, whereas SC superoxide dismutase (SOD) activity remained intact in those conditions. This potentially leads to the local overproduction of H2O2. The oxidized lipid squalene hydroperoxide accumulates at the surface of sun‐exposed skin in the summer and upon exposure to ultravoilet A (UVA) doses as low as 0.1 J cm−2 and adequate protection against excessive lipid peroxidation at times of UV exposure should be aimed for. We have been using the induction of lipid hydroperoxides at the skin surface by a single dose of UVA (1 J cm−2) as a model system to evaluate the protective effect of antioxidants in vivo. Topical treatment with the synthetic SOD/catalase mimetic molecule (EUK‐134) 1 h before UVA exposure reduced the level of lipid peroxides at the surface of UVA‐exposed skin but also baseline peroxide levels on non‐irradiated skin were reduced in a dose‐dependent fashion. In contrast to alpha‐tocopherol, EUK‐134 even reduced the level of lipid peroxides at the surface of UVA‐exposed skin when it was applied after irradiation. We confirmed that this salen–manganese complex was able to reduce squalene hydroperoxide levels in vitro, suggesting peroxidase‐like activity towards organic peroxides. These data support the concept that the synthetic SOD/catalase mimetic EUK‐134 might be able to compensate for seasonal deficiencies in antioxidant defense capacity at the skin surface, thereby contributing to an optimal protection of the skin against the accumulation of oxidative damage.

Prevention of oxidative damage that contributes to the loss of bioenergetic capacity in ageing skin

Skin ageing is a complex biological process related to a decline in physiological and biochemical performance. A decline in the mitochondrial energy production is a feature of ageing at the cellular level. This is partially attributed to excessive production of reactive oxygen species such as superoxide and hydrogen peroxide in aged individuals. We have investigated the effect of (glyc)oxidative stress on two biochemical targets relevant for the energy metabolism of the skin. First, we showed an age dependent decline in the activity of the hydrogen peroxide detoxifying antioxidant catalase in stratum corneum on a chronically sun-exposed site. Furthermore catalase was sensitive to peroxynitrite-induced in vitro inactivation. Catalase mimetics as well as peroxynitrite scavengers are proposed to maintain hydrogen peroxide detoxification pathways. The second target was creatine kinase, an enzyme that controls the creatine-creatine phosphate shuttle. Creatine kinase lost activity after in vitro glycation by methylglyoxal. This activity loss could be prevented by antiglycation actives. These data suggest that biomolecules involved in energy homeostasis become damaged by different sources of stress. Actives specifically selected for optimal protection against these stress situations will decrease skin vulnerability and prevent the premature loss of skin function.

The Flavonoid Luteolin Increases the Resistance of Normal, but Not Malignant Keratinocytes, Against UVB-Induced Apoptosis

Adequate protection of skin against the carcinogenic effects of UVB irradiation is essential. Flavonoids may have a conspicuous role in cancer prevention because of their antioxidant, anti-inflammatory, and growth-inhibitory effects. Therefore, we tested the effects of the flavone luteolin (LUT) on selected parameters of the sunburn response in normal human keratinocytes, exposed to physiological doses of UVB. LUT attenuated UVB-induced cell death through delay and inhibition of intrinsic apoptotic signaling. Moreover, LUT not only predominantly affected the mitochondrial apoptosis pathway through its antioxidant capacity, but also changed the balance of Bcl2 (B-cell leukemia/lymphoma 2)-family members. Furthermore, LUT had inhibitory effects on the UVB-induced release of the inflammatory mediators, IL-1alpha and prostaglandin-E(2). Using different cell lines derived from squamous cell carcinomas, we showed that LUT did not increase the resistance of malignant keratinocytes to UVB. Our data suggest that LUT inhibits different aspects of the sunburn response, which results ultimately in an increased survival of normal keratinocytes, whereas the sensitivity of malignant cells to UVB remain unchanged. Hence, LUT might have value in new photoprotective applications or improve existing ones.