Photoprotective and anti-skin-aging effects of eicosapentaenoic acid in human skin in vivo

J Lipid Res. 2006 May;47(5):921-30. doi: 10.1194/jlr.M500420-JLR200. Epub 2006 Feb 7.


Skin aging can be attributed to photoaging (extrinsic) and chronological (intrinsic) aging. Photoaging and intrinsic aging are induced by damage to human skin attributable to repeated exposure to ultraviolet (UV) irradiation and to the passage of time, respectively. In our previous report, eicosapentaenoic acid (EPA) was found to inhibit UV-induced matrix metalloproteinase-1 (MMP-1) expression in human dermal fibroblasts. Therefore, we investigated the effects of EPA on UV-induced skin damage and intrinsic aging by applying EPA topically to young and aged human skin, respectively. By immunohistochemical analysis and Western blotting, we found that topical application of EPA reduced UV-induced epidermal thickening and inhibited collagen decrease induced by UV light. It was also found that EPA attenuated UV-induced MMP-1 and MMP-9 expression by inhibiting UV-induced c-Jun phosphorylation, which is closely related to UV-induced activator protein-1 activation, and by inhibiting JNK and p38 activation. EPA also inhibited UV-induced cyclooxygenase-2 (COX-2) expression without altering COX-1 expression. Moreover, it was found that EPA increased collagen and elastic fibers (tropoelastin and fibrillin-1) expression by increasing transformin growth factor-beta expression in aged human skin. Together, these results demonstrate that topical EPA has potential as an anti-skin-aging agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cyclooxygenase 2 / biosynthesis
  • Eicosapentaenoic Acid / pharmacology*
  • Extracellular Matrix / drug effects
  • Gene Expression / radiation effects
  • Humans
  • MAP Kinase Kinase 4 / metabolism
  • MAP Kinase Kinase 4 / radiation effects
  • Male
  • Matrix Metalloproteinase 1 / biosynthesis
  • Matrix Metalloproteinase 9 / biosynthesis
  • Phosphorylation / radiation effects
  • Procollagen / biosynthesis
  • Procollagen / radiation effects
  • Proto-Oncogene Proteins c-jun / metabolism
  • Proto-Oncogene Proteins c-jun / radiation effects
  • Radiation-Protective Agents / pharmacology*
  • Skin Aging / drug effects*
  • Skin Aging / radiation effects
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Transforming Growth Factor beta3
  • Ultraviolet Rays
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • p38 Mitogen-Activated Protein Kinases / radiation effects


  • Procollagen
  • Proto-Oncogene Proteins c-jun
  • Radiation-Protective Agents
  • TGFB1 protein, human
  • TGFB2 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Transforming Growth Factor beta3
  • Eicosapentaenoic Acid
  • Cyclooxygenase 2
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1