The antiaging efficacy of retinol (ROL) has been explored mainly clinically in photoprotected skin sites and for high doses of ROL (0.4–1.6%). The objective of the study was to demonstrate the antiaging action of a low and tolerable dose of ROL (0.1%) ex vivo by measuring the expression of cellular retinoic-acid-binding protein II (CRABP2) and heparin-binding epidermal growth factor (HBEGF) by a histological evaluation of the epidermis and in vivo by assessing major aging signs and performing three-dimensional profilometry and digital imaging during a 9-month double-blind placebo-controlled study involving 48 volunteers. Finally, epidermal cell proliferation was evaluated using tryptophan fluorescence spectroscopy. Our results demonstrate that 0.1% ROL induced CRABP2 and HBEGF gene expression and increased keratinocyte proliferation and epidermal thickness. In human volunteers, topical application of a ROL-containing product improved all major aging signs assessed in our study (wrinkles under the eyes, fine lines and tone evenness). Moreover, tryptophan fluorescence increased in the active-agent-treated group and not in the placebo-treated group, indicating that cell proliferation was accelerated in vivo. These data demonstrate that a product containing a low dose (0.1%) of ROL promotes keratinocyte proliferation ex vivo and in vivo, induces epidermal thickening ex vivo and alleviates skin aging signs, without any significant adverse reaction.

Retinol is an ingredient used in cosmetic products for reducing the appearance of the signs of aging and photo-damage. Currently, most of these products contain 0.1% of retinol. However, at this concentration, some irritation can occur. We have evaluated in vitro and in a clinical study the potential efficacy of a combination of actives to improve the facial skin aging signs while using low concentration of retinol. We demonstrated, in vitro, that a chromone derivative, 5,7-di-hydroxy-2-methyl chromone (DMC), is able to enhance the collagen synthesis in culture of normal human dermal fibroblasts. The enhancement of retinol anti-wrinkle efficacy by DMC was confirmed in a small scale clinical trial. Specifically, a product associating low concentration of retinol (0.04%) and DMC (0.1%) in combination with low molecular weight hyaluronic acid fragments (50,000 Dalton of average molecular weight) has been applied topically for 8 weeks. Clinical results show significant improvement of various signs of facial skin aging such as wrinkles, pigmentary spots, tone unevenness, dullness and the overall photo-damage score. Improvements were still visible 4 weeks after the cessation of the test product application. This study demonstrates that significant lasting improvement of facial skin aging can be obtained with well tolerated low concentration of retinol when adequately formulated with other anti-aging ingredients.