Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Molecular basis of sun-induced premature skin ageing and retinoid antagonism


DAMAGE to skin collagen and elastin (extracellular matrix) is the hallmark of long-term exposure to solar ultraviolet irradiation1–3, and is believed to be responsible for the wrinkled appearance of sun-exposed skin4,5. We report here that matrix-degrading metalloproteinase messenger RNAs, proteins and activities are induced in human skin in vivo within hours of exposure to ultraviolet-B irradiation (UVB). Induction of metalloproteinase proteins and activities occurred at UVB doses well below those that cause skin reddening. Within minutes, low-dose UVB upregulated the transcription factors AP-1 and NF-KB, which are known to be stimulators of metalloproteinase genes6,7. All-transretinoic acid, which transrepresses AP-1 (ref. 8), applied before irradiation with UVB, substantially reduced AP-1 and metalloproteinase induction. We propose that elevated metalloprotein-ases, resulting from activation of AP-1 and NF-KB by low-dose solar irradiation, degrade collagen and elastin in skin. Such damage, if imperfectly repaired, would result in solar scars, which through accumulation from a lifetime of repeated low-dose sunlight exposure could cause premature skin ageing (photoageing).

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others


  1. Talwar, H. S., Griffiths, C. E. M., Fisher, G. J., Hamilton, T. A. & Voorhees, J. J. J. invest. Dermat. 105, 285–290 (1995).

    Article  CAS  Google Scholar 

  2. Lavker, R. M. J. invest. Dermat. 73, 559–566 (1979).

    Article  Google Scholar 

  3. Smith, J. G., Davidson, E. A., Sams, W. M. & Clark, R. D. J. invest. Dermat. 39, 347–350 (1962).

    Article  CAS  Google Scholar 

  4. Kligman, L. H. & Kligman, A. M. Photodermatology 3, 215–227 (1986).

    CAS  PubMed  Google Scholar 

  5. Wlaschek, M. et al. Photchem. Photobiol. 59, 550–556 (1994).

    Article  CAS  Google Scholar 

  6. Angel, P. et al. Cell 49, 729–739 (1987).

    Article  CAS  Google Scholar 

  7. Sato, H. & Seiki, M. Oncogene 8, 395–405 (1993).

    CAS  PubMed  Google Scholar 

  8. Salbert, G. et al. Molec. Endocr. 7, 1347–1356 (1993).

    CAS  PubMed  Google Scholar 

  9. Oikarinen, A., Kylmaniemi, M., Autio-Harmainen, A., Autio, P. & Salo, T. J. invest. Dermat. 101, 205–210 (1993).

    Article  CAS  Google Scholar 

  10. Saarialho-Kere, U. K., Pentland, A. P., Birkedal-Hansen, H., Parks, W. C. & Welgus, H. G. J. clin. Invest. 94, 79–88 (1994).

    Article  CAS  Google Scholar 

  11. Mauch, C., Krieg, T. & Bauer, E. A. Arch. Dermat. Res. 287, 107–114 (1994).

    Article  CAS  Google Scholar 

  12. Eisen, A. Z. J. Invest. Dermat. 52, 442–448 (1969).

    Article  CAS  Google Scholar 

  13. Devary, Y., Gottlieb, R. A., Lau, L. F. & Karin, M. Molec. cell. Biol. 11, 2804–2811 (1991).

    Article  CAS  Google Scholar 

  14. Angel, P. & Karin, M. Matrix Suppl. 1, 156–164 (1992).

    CAS  PubMed  Google Scholar 

  15. Quinones, S., Buttice, G. & Kurkinen, M. Biochem. J. 302, 471–477 (1994).

    Article  CAS  Google Scholar 

  16. Frisch, S. M. & Morisaki, J. H. Molec. cell. Biol. 10, 6524–6532 (1990).

    Article  CAS  Google Scholar 

  17. Nicholson, R. C. et al. EMBO J. 9, 4443–4454 (1990).

    Article  CAS  Google Scholar 

  18. Yang-Yen, H. F. et al. Cell 62, 1205–1215 (1990).

    Article  CAS  Google Scholar 

  19. Schule, R. et al. Cell 62, 1217–1226 (1990).

    Article  CAS  Google Scholar 

  20. Pfahl, M. Endocr. Rev. 5, 651–658 (1993).

    Google Scholar 

  21. Fisher, G. J. et al. J. biol. Chem. 269, 20629–20635 (1994).

    CAS  PubMed  Google Scholar 

  22. Weinstein, G. D. & Boucek, R. J. J. invest. Dermat. 35, 227–229 (1960).

    Article  CAS  Google Scholar 

  23. Bailly, B. S. et al. J. invest. Dermat. 94, 47–51 (1990).

    Article  CAS  Google Scholar 

  24. Rafal, E. S. et al. New. Engl. J. Med. 326, 368–374 (1992).

    Article  CAS  Google Scholar 

  25. Hill, P. A. et al. Biochem. J. 308, 167–175 (1995).

    Article  CAS  Google Scholar 

  26. Fisher, G. J. et al. J. invest. Dermat. 96, 699–707 (1991).

    Article  CAS  Google Scholar 

  27. Hu, C. L., Crombie, G. & Franzblau, C. Analyt. Biochem. 88, 638–643 (1978).

    Article  CAS  Google Scholar 

  28. Hibbs, M. S., Hasty, K. A., Seyer, J. M., Kang, A. H. & Mainardi, C. L. J. biol. Chem. 260, 2493–2500 (1985).

    CAS  PubMed  Google Scholar 

  29. Werb, Z., Tremble, P. M., Behrendtsen, O., Crowley, E. & Damsky, C. H. J. Cell Biol. 109, 877–889 (1989).

    Article  CAS  Google Scholar 

  30. Murphy, G. et al. Biochem. J. 258, 463–472 (1989).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and permissions

About this article

Cite this article

Fisher, G., Datta, S., Talwar, H. et al. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature 379, 335–339 (1996).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing