The University Record, November 19, 1997

Researchers identify process that starts skin aging

By Sally Pobojewski
Medical Center Public Relations

U-M scientists have identified a biochemical process, that, when triggered by ultraviolet radiation in sunlight, leads to premature skin aging. The study, published in the Nov. 13 issue of the New England Journal of Medicine, shows that surprisingly small amounts of exposure to sunlight are enough to start the premature aging process.

"From a public health standpoint, the major significance of this study is the evidence indicating that exposure to a few minutes of sunlight periodically over several years can lead to premature skin aging," says John J. Voorhees, the Duncan O. and Ella M. Poth Distinguished Professor of Dermatology and the study's senior author. "This is far less than the exposure required to produce any visible reddening of the skin."

"Although sunscreens help prevent skin cancer and sunburn, they may not protect against skin photoaging, since it appears that sunburn and photoaging may be caused by different kinds of ultraviolet sunlight," says Gary J. Fisher, associate research scientist in dermatology and the study's lead author.

"New sunscreens and drugs may need to be developed to combat premature aging. We found that pretreating skin with retinoic acid-the business end of vitamin A or retinol-before UV exposure inhibited the biochemical changes leading to premature skin aging."

Major points in the article included:

  • Repeated exposure to ultraviolet radiation in sunlight causes skin to age prematurely-a condition called photoaging. Photoaged skin has wrinkles, brown spots, changes in pigmentation and surface roughness. These skin changes are not part of the natural, normal aging process.

  • The most likely cause for the visible wrinkling associated with photoaging is the breakdown of collagen-the major structural material in skin. Ninety-five percent of the dermis, or underlying layer of skin, is made of collagen.

  • Ultraviolet radiation in sunlight triggers a molecular chain reaction which produces large amounts of enzymes called matrix metalloproteinases (MMPs). MMPs break apart and degrade collagen. While skin has a natural ability to repair damaged collagen, these repairs are never perfect.

    Tiny amounts of at first invisible scar tissue build up over time and eventually become visible as wrinkles (photoaging).

  • U-M scientists found that MMP levels in dermal skin were directly associated with the length and frequency of exposure to ultraviolet light. Exposure to small amounts of UV (too small to cause skin redness) every other day was enough to induce sustained MMP production at high levels in the individuals in this study.

  • Pretreating skin with retinoic acid before UV exposure inhibited production of MMPs and resulting collagen damage by 70 to 80 percent in the U-M study. Because it blocks MMP production, retinoic acid should also prevent photoaging, although more research will be needed to know for sure.

  • The possibility of photoaging prevention is a surprising outcome of this study. Retinoic acid is already approved by the FDA to treat photoaging that has already happened. But until now, the possibility that vitamin A and retinoic acid might prevent photoaging has not been seriously considered.

  • While retinoic acid blocks MMP production, it has no effect on the skin's ability to produce enzymes called Tissue Inhibitors of MetalloProteinases (TIMPs) which naturally prevent MMP-induced collagen damage. Retinoic acid may prevent photoaging by reducing amounts of harmful enzymes in the dermis, while maintaining normal levels of tissue-protecting proteins (TIMPs).

    Future research will attempt to discover how retinoic acid blocks MMP activation when skin is exposed to ultraviolet light. U-M scientists are exploring the role played by a protein called AP-1, which "turns on" genes in skin cells causing them to produce both MMPs and TIMPs.

    In addition to Voorhees and Fisher, co-investigators on the study were ZengQuan Wang, Subhash C. Datta, James Varani and Sewon Kang, all from the Department of Dermatology.