Highlights on the communication between dermis and epidermis during aging

Summary: Abstract Body: Dermis and epidermis cannot be reduced to two separate and autonomous entities. For several years, new studies have been emerging to analyze the influence of dermal aging on the epidermis, by studying mechanisms of intercellular communication. This study aimed to investigate the impact of aging on the communication systems in place from the dermis to the epidermis. First, a proteomic study was conducted on the secretome of young and aged fibroblasts, enabling the detection of 335 proteins. A bio-informatic analysis reveals that 128 of these proteins are involved in communication paths, with an enrichment in four cellular processes related to communication originating in the dermal compartment (regulation of IGF-1 pathway, signaling of growth factors, signaling of inflammation and cellular interactions). Moreover, our results reveal a deregulation of more than half of these proteins in the secretome from aged fibroblasts. To go further in the investigation of intercellular communication, extracellular vesicles (EVs) were isolated from secretomes. The expression of 9 miRNAs, known as inhibitors of epidermal biological pathways and transported in EVs, was measured in young and aged models. Results reveal a significant increase in their expression with aging, suggesting a communication shortfall that could induce an alteration in epidermal biological functions. To corroborate this hypothesis, old keratinocytes were exposed to aged fibroblasts secretome. This latter significantly decreases keratinocyte proliferation and differentiation, cell cohesion and the anchoring of the dermal-epidermal junction, thus accentuating the impact of aging on the biological functions of the epidermis. Altogether, these results give an overview of the intercellular communication actors deregulated during skin aging. This investigation paves the way to innovative developments allowing to restore the communication systems from the dermis to improve the epidermal functionalities. Laetitia Marchand¹, Laurie Verzeaux¹, Clément Nivet¹, Elodie Aymard¹, Hélène Muchico¹, Brigitte Closs¹ 1. SILAB, Brive, France. Cell Communication Networks and Stromal Biology