The 21st Century Approach To Epidermal Health and Hydration: Endogenous Hyaluronic Acid

HYALURONIC ACID: HOW SUCH A SIMPLE MOLECULE GOT SO COMPLICATED Hyaluronic acid (HA), probably the most recognized ingredient in the skincare industry, has undergone a remarkable scientific evolution since it was first isolated in 1934.1 Despite its widespread use as a topical skincare ingredient and injectable dermal filler, relatively little is known about the cellular pathways that control HA in normal and diseased skin. This non-sulfated glycosaminoglycan (GAG) is formed by repeating units (up to 30,000) of D-glucuronic acid and N-acetyl-d-glucosamine, producing molecules ranging from 1x105-107 Da in size (2-25mm length) (Figure 1A). The main roles assigned to HA to date have been as a space filler and water-binder although its high turnover rate (half-life two to three hours in epidermis and less than one day in dermis) suggest additional roles in skin biology. Moreover, the effects of retinoic acid, which triggers epidermal HA accumulation, and hydrocortisone, which decreases epidermal HA, support the hypothesis of a regulatory effect of HA on epidermal homeostasis. Epidermal proliferation (hyperplasia/atrophy) and terminal differentiation (stratum corneum thinning /thickening) are strongly correlated with HA-levels.2,3,4 Recent scientific discoveries have challenged the outdated view of HA as a simple space filler, elevating it to a role as a key active regulator of dynamic processes such as keratinocytes proliferation and differentiation, barrier formation, inflammation, oxidative stress, skin hydration, cell survival and wound healing. Physiological levels of HA in the dermis and epidermis (0.5 and 0.1 mg/kg, respectively) are controlled by four key processes: • Synthesis, • Deposition, • Binding to hyaladherins (see below), and • Degradation (Figure 1 B).5 Synthesis of HA occurs on the cell surface by a family of membrane-bound enzymes called hyaluronic acid synthases