Wrinkle Removers, Backed by Science

Nostrums that promise to smooth wrinkled skin are a staple of snake-oil salesmen everywhere, but now there is strong evidence that certain kinds of treatment are effective. Over the past decade, researchers have been learning which treatments work, and why.

The key is a growing understanding of the skin’s connective tissue, called the dermal collagen, and a recognition that damage to the mechanical properties of the collagen outside the skin cells, and not necessarily genetic damage to the cells themselves, causes wrinkled skin.

A recent review in The Archives of Dermatology concludes that three anti-aging treatments are proven clinically effective: the topical application of retinol; carbon dioxide laser resurfacing; and injection of hyaluronic acid, a moisture-retaining acid that occurs naturally in the skin. Each depends on the same mechanism, the interaction of skin cells called fibroblasts with the collagen they produce.

“This is an area where there’s a lot of hype and not much substance,” said David J. Leffell, a professor of dermatology and surgery at Yale who was not involved in the review. But, he said, this study is “good science.”

Theory and experiment back these treatments, the authors write. Fibroblasts — connective tissue cells — secrete a complex group of polysaccharides and proteins that creates collagen, which gives the skin shape and elasticity and supports the blood vessels that permeate it. The network of collagen tissue is maintained by its mechanical tension with these skin cells.

Skin deteriorates as it ages, but its exposure to sunlight inhibits the ability of fibroblasts to produce collagen. The hands, face, neck and upper chest all suffer more than unexposed skin, and light-pigmented people wrinkle more readily than others. This damage, the authors write, is essentially an accelerated version of chronological aging. Ultraviolet radiation induces production of the same enzymes that degrade collagen with age.

Collagen fibers last as long as 30 years. But with age and ultraviolet exposure, they deteriorate and fragment, and fragmented collagen impairs the collagen-producing function of the fibroblasts that created it. As the fragmented collagen accumulates, new collagen production declines, the connections between the fibroblasts and the collagen weaken, and the skin, now lacking support, begins to wrinkle.

But there are treatments that counter this process. Topical application of retinol, a form of vitamin A, was the first to be proved useful. Although the molecular pathways are not well understood, retinol causes new collagen to form in chronologically aged skin and in skin damaged by ultraviolet light.

Skin creams with retinol are available over the counter, but many do not indicate the concentration of the active ingredient. “Many products just refer to retinol or vitamin A as a buzzword,” said Gary J. Fisher, the lead author of the review and a professor of dermatology at the University of Michigan.

Concentrations of 0.2 to 0.6 percent are enough, Dr. Fisher said, but preparations strong enough to have an effect can also have a side effect, a rash called retinoid dermatitis. Dr. Fisher’s advice is to stop using it if a rash occurs. The rash can sometimes be avoided if the concentration is increased gradually.

Retinol also makes the skin more sensitive to damage from ultraviolet light, so protection from the sun while using it is essential. “O.T.C. products tend to try to walk the line between effects and side effects,” Dr. Fisher said. “But many intentionally keep the concentration too low to have any benefit.”

Dr. Robyn S. Gmyrek, an assistant professor of dermatology at Columbia University, is also skeptical of over-the-counter wrinkle creams. “If something shows true biological activity, it’s regulated as a drug,” she said. “A cream bought over the counter is certainly not going to do what prescription-strength retinol will do.” Dr. Gmyrek was not involved in the study.

Carbon dioxide laser resurfacing is another well-tested treatment for wrinkles. The laser removes thin layers of skin without damaging surrounding tissue. As the wound heals, new collagen is produced. The treatment works first by inducing high levels of matrix metalloproteinase, or MMP, an enzyme that destroys fragmented collagen. Then it reduces MMP and increases the production of new and undamaged replacement material. The procedure is also used for removing scars, warts and birthmarks.

Healing takes two to three weeks, and the wound has to be cleaned with saline or diluted vinegar and treated with ointments to prevent scarring. In most cases, the procedure is done only once, Dr. Fisher said, and lasts many years.

There are now some less invasive laser procedures, the authors write, but their effectiveness is doubtful.

The third effective treatment is injecting a form of hyaluronic acid, similar to a substance the skin normally produces, into the dermis that underlies the wrinkles. This was originally designed as a space filler, with no intended physiological effect. But as the injection stretches the dermis, the fibroblasts respond by producing more collagen and less MMP. The authors cite studies that have demonstrated that increased collagen production is visible within a month after the injection. The benefit lasts about six months, Dr. Fisher said.

This type of hyaluronic acid, he said, should not be confused with hyaluronic acid in some topical cosmetic products. Rubbing such products on the skin will not stimulate collagen production.
Do the benefits of these treatments outweigh the risks?

“It’s a matter of the kind of problem a person perceives and how he wants to deal with it,” Dr. Fisher said. “For these treatments, which have sound research behind them, and for people who want to improve their appearance, the benefits far outweigh any problems.”

The authors have no ties to companies that make skin care products, but the University of Michigan, where they teach, has patents on the use of matrix metalloproteinase inhibitors in the treatment and prevention of aging skin.

By NICHOLAS BAKALAR @ The New York Times



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