Extracellular matrix in cutaneous ageing: the effects of 0.1% copper-zinc malonate-containing cream on elastin biosynthesis

Exp Dermatol. 2009 Mar;18(3):205-11. doi: 10.1111/j.1600-0625.2008.00783.x.


Cutaneous ageing, as visualized at the exposed areas of skin, reflects dramatic alterations in the structure and function of the extracellular matrix of connective tissues. Among them, the elastic fibre network, which is responsible for the physiological elasticity and resilience of normal skin, undergoes degradative changes leading to loss of functional elastic fibres. A potential strategy to counteract these degenerative changes entails topical application of a compound that may lead to regeneration of the elastic fibre network. In this study, we have evaluated the effects of a bi-metal, 0.1% copper-zinc malonate-containing cream that has been shown to efface wrinkles in clinical trials. An effect on elastin biosynthesis and elastic tissue accumulation in skin biopsies was observed in 21 female patients with photoaged facial skin, as measured at baseline and at 6 weeks of treatment. Histopathological evaluation revealed evidence of elastic fibre regeneration, including those extending perpendicularly towards the dermo-epidermal junction within the papillary dermis. Elastin biosynthesis, measured by semi-quantitative immunofluorescence with an antibody recognizing only the newly synthesized, uncrosslinked tropoelastin molecules, suggested statistically significant enhancement of elastin biosynthesis by the bi-metal compound when applied twice daily. Accumulation of elastic fibres was confirmed by assay of desmosine, an elastin-specific crosslink compound. These results suggest that the bi-metal, 0.1% copper-zinc malonate-containing cream has the propensity to increase elastin synthesis in human skin in vivo, and that regeneration of elastic fibres may contribute to wrinkle effacement in female patients with photoaged facial skin.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Copper / administration & dosage
  • Copper / pharmacology*
  • Desmosine / metabolism
  • Double-Blind Method
  • Elastin / metabolism*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Female
  • Humans
  • Malonates / administration & dosage
  • Malonates / pharmacology*
  • Middle Aged
  • Ointments
  • Skin / drug effects
  • Skin / metabolism*
  • Skin / pathology
  • Skin Aging / drug effects
  • Skin Aging / physiology*
  • Tropoelastin / metabolism
  • Zinc / administration & dosage
  • Zinc / pharmacology*


  • Malonates
  • Ointments
  • Tropoelastin
  • Desmosine
  • Copper
  • Elastin
  • malonic acid
  • Zinc