Science

Yuan Shao, Tianyuan He, Gary J. Fisher, John J. Voorhees, and Taihao Quan

OBJECTIVE
Retinoic acid has been shown to improve the aged-appearing skin. However, less is known about the anti-aging effects of retinol (ROL, vitamin A), a precursor of retinoic acid, in aged human skin in vivo. This study aimed to investigate the molecular basis of retinol anti-aging properties in naturally aged human skin in vivo.

METHODS
Sun-protected buttock skin (76±6 years old, n=12) was topically treated with 0.4% ROL and its vehicle for seven days. The effects of topical ROL on skin epidermis and dermis were evaluated by immunohistochemistry, in situ hybridization, Northern analysis, real-time RT-PCR, and Western analysis. Collagen fibrils nanoscale structure and surface topology were analysed by atomic force microscopy.

RESULTS
Topical ROL shows remarkable anti-aging effects through three major types of skin cells: epidermal keratinocytes, dermal endothelial cells and fibroblasts. Topical ROL significantly increased epidermal thickness by stimulating keratinocytes proliferation and upregulation of c-Jun transcription factor. In addition to epidermal changes, topical ROL significantly improved dermal extracellular matrix (ECM) microenvironment; increasing dermal vascularity by stimulating endothelial cells proliferation and ECM production (type I collagen, fibronectin, and elastin) by activating dermal fibroblasts. Topical ROL also stimulates TGF-β/CTGF pathway, the major regulator of ECM homeostasis, and thus enriched the deposition of ECM in aged human skin in vivo. 0.4% topical ROL achieved similar results as seen with topical retinoic acid, the biologically active form of ROL, without causing noticeable signs of retinoid side effects.

CONCLUSION
0.4% topical ROL shows remarkable anti-aging effects through improvement of the homeostasis of epidermis and dermis by stimulating the proliferation of keratinocytes and endothelial cells, and activating dermal fibroblasts. These data provide evidence that 0.4% topical ROL is a promising and safe treatment to improve naturally aged human skin.