Wrestling with wrinkles: scientists are closing in on the secrets of skin aging - includes related article on wrinkle measurement

Science News, Sept 24, 1988 by Rick Weiss

Wrestling With Wrinkles Scientists are closing in on the secrets of skin aging

Ancient Rome's poet laureate of love never heard of topical tretinoin, or Retin-A, the antiwrinkle cream that recently has gained medical and popular celebrity. But his words document skin wrinkling as an age-old concern, and help explain the marketplace mania that followed publication of research earlier this year showing tretinoin's reversal of "dermatoheliosis," or sun-induced skin aging.

Sales of the drug have "skyrocketed" since publication of that research in the Jan. 22/29 JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (JAMA), according to its manufacturer, Ortho Pharmaceutical in Raritan, N.J. The article featured striking, full-color "before and after" pictures of tretinoin-treated skin that showed a marked reduction in the number of wrinkles and an obvious fading of "age spots" and sunlight-induced freckles.

Scientists still don't understand the mechanism by which tretinoin exerts its effects. Indeed, the phenomenon of aging itself remains one of the great mysteries of biological science. But inspired by tretinoin's apparent ability to reverse at least some of the obvious signs of skin aging, and equipped with a new generation of mechanical and molecular biological tools, dermatologists at last are gaining insight into the enigmatic relationship between biology and time. And while skin aging is of obvious interest to anyone concerned about personal appearance, its study appeals to more than simple vanity.

"Many of the processes associated with aging are the same both in the skin and in other tissues," says Jouni J. Uitto, chairman of the department of dermatology at Jefferson Medical College in Philadelphia. Aging research has qften focused on the skin, if for no other reason than "the skin is very accessible."

Moreover, says Richard G. Cutler, a research chemist with the National Institute on Aging, the skin performs a broad range of biological functions. So an understanding of how it ages--and of how to slow that process -- may add to our understanding of age-related degeneration in a variety of other organ systems. In many ways, he says, skin is an ideal model of biological deterioration.

"A skin cell, before it falls on the floor, has a predestination with death," Cutler says flatly. But senescence is not simply a matter of running out of cells or enzymes, he adds. "Aging is more subtle than that."

Subtlety, of course, is in the eye of the beholder, and the aging process may seem anything but subtle to the owner of a wrinkled integument. To a dermatologist peering into a microscope, the situation looks even worse.

Aged skin is thinner than younger skin, and is characterized by an increase in cellular disorganization, says Lynne T. Smith of the University of Washington in Seattle. Where healthy basal cells once stood lined up in neat columns within the epidermis, or outer layer of skin, scientists find them in disarray--evidence of a breakdown in the normal process of cellular proliferation and organization.

With age, collagen fibers --important in maintaining skin integrity -- decrease in number, organization and density. Smooth, ribbon-like fibers of elastin, responsible for skin's ability to "snap back" to shape after being stretched, get coarser, denser and less resilient, especially where the skin has been exposed to sunlight.

Tiny blood vessels in the dermis, the deeper layer of skin, become thick-walled yet leakier, and there is a general loss of hair, nerve cells, sweat ducts and sebaceous glands that produce fatty secretions called sebum.

In short, says Albert Kligman, a dermatologist at the University of Pennsylvania in Philadelphia, "the whole business of [skin] aging is detrimental. It's thumbs down." Nonetheless, he adds, pointing to a picture of a sun-wrinkled woman whose face resembles a severely dried apple, "no person should ever have to look like this."

The implication is that whole some aspects of aging may be unavoidable, many age-associated biological changes are not. In the case of skin and probably many other parts of the body, say Kligman and others, such changes -- especially those triggered by sunlight or certain oxygen-dependent reactions -- can be prevented and even reversed.

Skin aging can be thought of as a combination of two processes: intrinsic, chronological aging, which appears to be a genetically programmed sensecence; and extrinsic, accumulated environmental damage such as photoaging -- the result of a series of chemical reactions triggered by exposure to sunlight.

Scientists remain uncertain whether anything can be done to alter the course of intrinsic aging. Recent research using molecular biological techniques on cultured cells shown that individual cells -- unfamiliar as they may be with the concept of time -- seem to "know" how old they are, and age in predictable ways.

"Cells don't actually measure time," notes Vincent Cristofalo, director of the Center for the Study of Aging at the University of Pennsylvania in Philadelphia. "Aging isn't measured by the passage of time, but rather by some sort of sequential molecular events that the cell can understand, but which we can only keep track qf by measuring the rotation of the Earth on its axis or its movement around the sun."