403 Glyoxal induces senescence in in vitro skin models

Abstract

Senescence is a well-known cellular event characterized by specific markers like a permanent cell proliferation arrest and the secretion of messenger molecules forming the Senescence-Associated Secretory Phenotype (SASP). The SASP composition depends on many factors such as the cell type and the nature of the stress that induced senescence. Since the skin constitutes a barrier with the external environment, it is particularly subjected to different types of stresses and thus to premature cellular aging. In this study, we have demonstrated that glyoxal provokes senescence in our skin in vitro models. Indeed, application of glyoxal on keratinocytes during the reconstruction induced a senescent phenotype of epidermis with a thinning of epidermal thickness (H&E), an increase of senescent markers (p16), an increase of inflammatory cytokine (IL1a), and a decrease of terminal differentiation epidermal protein expression (filaggrin, loricrin). Our study provides evidence that glyoxal can affect keratinocyte function and act as a driver of human skin aging. Hence, senotherapeutics aimed at modulating glyoxal-associated senescent phenotype, could be relevant to prevent the aging process in skin. These innovative in vitro models have been used to develop and screen ingredients. Results allowed to select ingredients with high potential to fight against consequences of glyoxal stress.