Molecular basis of retinol anti-ageing properties in naturally aged human skin in vivo

Int J Cosmet Sci. 2017 Feb;39(1):56-65. doi: 10.1111/ics.12348. Epub 2016 Jul 4.


Objective: Retinoic acid has been shown to improve the aged-appearing skin. However, less is known about the anti-ageing 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 ROL anti-ageing 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 7 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-ageing 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-ageing 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 the naturally aged human skin.

Keywords: TGF-β; extracellular matrix; retinoid; skin ageing; vascularity.

MeSH terms

  • Aging / drug effects*
  • Collagen / metabolism
  • Connective Tissue Growth Factor / metabolism
  • Humans
  • Microscopy, Atomic Force
  • Skin / blood supply
  • Skin / cytology
  • Skin / metabolism
  • Transforming Growth Factor beta / metabolism
  • Vitamin A / pharmacology*


  • CCN2 protein, human
  • Transforming Growth Factor beta
  • Vitamin A
  • Connective Tissue Growth Factor
  • Collagen