[809] Skin Aging

Our laboratory is mainly interested in the molecular mechanisms of skin aging. Our recent studies allowed to characterize the role of CD44 and the importance of its interaction with hyaluronate (HA) in skin aging. CD44 is a polymorphic transmembrane glycoprotein and the major surface receptor of HA, which can form complexes with matrix metalloproteinase (MMP-7), the precursor of heparin-binding epidermal growth factor (HB-EGF), (pro- HB-EGF) and one of its receptors erbB1. We demonstrated that two major functions of CD44 in mouse skin are (i) the regulation of keratinocyte proliferation in response to extracellular stimuli, and (ii) the maintenance of local HA homeostasis. We observed a decrease in the expression of CD44 and epidermal HA in extreme skin atrophy of elderly subjects for which we proposed the term "dermatoporosis". HA fragments (HAFs) of defined size correct skin atrophy in mice and humans by a CD44-dependent mechanism and topical retinoids and HAFs show a synergistic effect in this correction. We also demonstrated that Lrig1-positive stem cells are retained and Wnt/β-catenin signaling is decreased in the epidermis of senescent skin. Currently we are working on the role of senescent cells in skin aging.