Azelaic acid reduced senescence-like phenotype in photo-irradiated human dermal fibroblasts: possible implication of PPARγ

Exp Dermatol. 2013 Jan;22(1):41-7. doi: 10.1111/exd.12066.


Azelaic acid (AzA) has been used for the treatment for inflammatory skin diseases, such as acne and rosacea. Interestingly, an improvement in skin texture has been observed after long-time treatment with AzA. We previously unrevealed that anti-inflammatory activity of AzA involves a specific activation of PPARγ, a nuclear receptor that plays a relevant role in inflammation and even in ageing processes. As rosacea has been considered as a photo-aggravated disease, we investigated the ability of AzA to counteract stress-induced premature cell senescence (SIPS). We employed a SIPS model based on single exposure of human dermal fibroblasts (HDFs) to UVA and 8-methoxypsoralen (PUVA), previously reported to activate a senescence-like phenotype, including long-term growth arrest, flattened morphology and increased synthesis of matrix metalloproteinases (MMPs) and senescence-associated β-galactosidase (SA-β-gal). We found that PUVA-treated HDFs grown in the presence of AzA maintained their morphology and reduced MMP-1 release and SA-β-galactosidase-positive cells. Moreover, AzA induced a reduction in ROS generation, an up-modulation of antioxidant enzymes and a decrease in cell membrane lipid damages in PUVA-treated HDFs. Further evidences of AzA anti-senescence effect were repression of p53 and p21, increase in type I pro-collagen and abrogation of the enhanced expression of growth factors, such as HGF and SCF. Interestingly, PUVA-SIPS showed a decreased activation of PPARγ and AzA counteracted this effect, suggesting that AzA effect involves PPARγ modulation. All together these data showed that AzA interferes with PUVA-induced senescence-like phenotype and its ability to activate PPAR-γ provides relevant insights into the anti-senescence mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cellular Senescence / drug effects*
  • Cellular Senescence / radiation effects
  • Collagen Type I / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Dermatologic Agents / pharmacology*
  • Dicarboxylic Acids / pharmacology*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism*
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Matrix Metalloproteinase 1 / metabolism
  • Methoxsalen / pharmacology
  • PPAR gamma / metabolism*
  • PUVA Therapy
  • Phenotype
  • Phospholipids / metabolism
  • Photosensitizing Agents / pharmacology
  • Procollagen / metabolism
  • Reactive Oxygen Species / metabolism
  • Stem Cell Factor / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Ultraviolet Rays
  • beta-Galactosidase / metabolism


  • CDKN1A protein, human
  • Collagen Type I
  • Cyclin-Dependent Kinase Inhibitor p21
  • Dermatologic Agents
  • Dicarboxylic Acids
  • PPAR gamma
  • Phospholipids
  • Photosensitizing Agents
  • Procollagen
  • Reactive Oxygen Species
  • Stem Cell Factor
  • Tumor Suppressor Protein p53
  • Hepatocyte Growth Factor
  • beta-Galactosidase
  • Matrix Metalloproteinase 1
  • azelaic acid
  • Methoxsalen