Anti-aging Effects of Retinoid Hydroxypinacolone Retinoate on Skin Models

Nora Ruth and Thomas Mammone

Tretinoin, also known as all-trans retinoic acid (ATRA), has been well-known for its anti-aging effects on skin since the 1980s.1,2 ATRA functions by activating the nuclear retinoic acid family of receptors (RARs), which control gene transcription by binding to retinoic acid responsive elements (RAREs) in DNA.3 Retinoids are thought to reduce wrinkles by increasing type I procollagen expression and inhibiting dermal collagen degradation by matrix metalloproteinases in the upper papillary dermis.2,4 Skin texture is improved by increasing epidermal proliferation and differentiation, compacting stratum corneum, thickening of the granular layer, and increasing epidermal and dermal glycosaminoglycan deposition.2,4,5 However, despite all of these benefits, retinoids such as retinol, retinaldehyde, and ATRA, suffer from the limitations of causing skin irritation, photochemical instability, and concerns about toxicity that have hindered or limited their use in cosmetic products.3 Typically, milder retinoid derivatives such as retinol esters, are used, which must first be metabolized to more active forms by several enzymatic steps in the skin, which reduces their potency. Therefore, it is desirable to find new molecules that have increased retinoic acid– like activity without the negative side effects.6 Hydroxypinacolone retinoate (HPR), a cosmetic grade ester of ATRA (Fig. 1), is unique in that it possesses innate retinoic acid activity, binding directly with retinoid receptors without the need for metabolic breakdown to more biologically active forms. It has been demonstrated to be more stable and cause less skin irritation than ATRA.7,8 In this study, we used an in vitro method with organotypic skin models to investigate the physiological effects of a more stable retinoid, hydroxypinacolone retinoate, to determine whether it could be a preferred alternative to the standard first-generation retinoids for cosmetic use.


EFT-300, skin longevity, wrinkles, collagen degradation, tretinoin, all-trans retinoic acid (ATRA), hydroxypinacolone retinoate, retinoids, jojoba oil, retinol esters, anti-aging, IL-1a, procollagen Type I C-peptide

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