Potentially beneficial effects of rhamnose on skin ageing: an in vitro and in vivo study.

OBJECTIVE: Recent findings showed that skin ageing preferentially affects human papillary dermal fibroblasts suggesting that the papillary dermis represents a critical zone altered by skin ageing. Based on these findings, we investigated the potential anti-ageing effect of rhamnose. METHODS: We investigated the potential anti-ageing effect of rhamnose using in vitro reconstructed skin containing fibroblasts obtained either from young or old donors, and in vivo clinical investigation. RESULTS: We detected positive effects of rhamnose in both epidermal and dermal compartments of in vitro reconstructed skin. Moreover, we were able to show that such in vitro findings were also obtained in vivo including an effect on collagen IV and procollagen I production. CONCLUSION: We provide evidence that rhamnose has a potentially beneficial effect on papillary dermis and dermal-epidermal junction, both of the areas which are affected by skin ageing.

OBJECTIF: Le vieillissement de la peau humaine affecte particulièrement les fibroblastes du derme papillaire suggérant que le derme papillaire représente une zone importante altérée par le vieillissement. A partir de ces résultats, nous avons étudié le potentiel effet anti-âge du rhamnose. METHODES: Le potentiel effet anti-âge du rhamnose a été étudié in vitro en utilisant un modèle de peau reconstruite contenant des fibroblastes isolés à partir d'un donneur jeune et d'un donneur âgé et dans une étude clinique in vivo. RÉSULTATS: Nous avons observé un effet positif du rhamnose dans le compartiment épidermique et dermique de la peau reconstruite in vitro. En outre, nous avons pu montrer in vivo comme in vitro, un effet sur la production du collagène IV et du procollagène I. CONCLUSION: Le rhamnose a un effet bénéfique potentiel sur deux zones touchées par le vieillissement cutané, le derme papillaire et la jonction dermo-épidermique.

Glycation stimulates cutaneous monocyte differentiation in reconstructed skin in vitro.

Glycation reaction is a recognized mechanism related to chronological aging. Previous investigations in cutaneous biology have considered the effect of glycation on the dermal matrix molecules, involved in tissue stiffening during skin aging. However, little is known about a possible direct effect of glycation upon cell differentiation. To address such issue, the effect of glycation has been re-investigated in a reconstructed skin model integrating monocytes that are cells capable of differentiating according to different pathways. The results showed that, in the absence of glycation, a small number of these CD45+ cells could differentiate either into dendritic-like cells (DC-SIGN+, BDC1a+, DC-LAMP+) or macrophage- like cells (CD14+, CD68+, CD163+) whereas, with glycation, the number of monocytes, dendritic cells, macrophage-like cells were found surprisingly increased. In-vivo our results showed also that dendritic and macrophage-like cells were increased and suggest a possible link with the age-dependent glycation level in the skin. In addition, we found that, unlike fibroblasts incorporated in the reconstructed skin, these cells expressed specific receptors for AGEs (RAGE and SRA). Taken altogether, our data show that cells of the monocyte lineage, in the presence of AGEs, can differentiate into dendritic or macrophage-like cells and could lead to a micro inflammatory environment.

Reaction of glycation and human skin: the effects on the skin and its components, reconstructed skin as a model.

Skin is affected by the aging process and numerous modifications are observed. In human, with time the skin becomes drier, thinner, spots appear, elasticity decreases and stiffening increases, together with the appearance of wrinkles. These observations result from the overlapping of an intrinsic chronological aging (individual, genetic) and of an extrinsic aging (dependent on external factors like UV, pollution and lifestyle). One of the causes of aging is the appearance of the Advanced Glycosylation End Products (AGEs) during life. The glycation reaction results from a non-enzymatic reaction between a sugar and a free amine group of Lys, Arg amino acids in proteins. This reaction does not occur only in the skin, indeed, AGEs are also found in the kidney, lens, vessels, etc. These products are also responsible, because of their localization, of some pathologies related to diabetes. AGEs provoke biological modifications implying an activation of molecules synthesis (extracellular matrix, cytokines) and enzyme activation of matrix degradation (metalloproteinases). The UV effect on AGEs (like pentosidine) generates reactive oxygen species (ROS) in the extracellular matrix which could lead to additional deleterious effects. Molecules are described in the literature as inhibitors to this irreversible reaction i.e. aminoguanidine. To understand the consequences of the glycation in the skin, a system of reconstructed skin was developed with a collagen modified by glycation for the dermal component. In this system we observed that dermis and epidermis are both modified due to glycation (macromolecules synthesis, cytokines, metalloproteinases) and it is possible to test inhibitors of this reaction. In conclusion, in skin, glycation is involved in a very complex aging process and simultaneously affect, directly and indirectly, certain cells, their synthesis and the organization of the matrix.