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

New research indicates that after a skin cell has lived out the lifetime allotted by its genetic code, certain membrane receptors in the cell become insensitive to growth factors that normally trigger DNA replication and cell division.

"Proliferation is the most basic and obvious ability that cells lose with age," Cristofalo said at a recent symposium on the biology of skin aging, convened at Jefferson Medical College. "With age, there's a lengthening of generation time until an arrested state."

In contrast to this seemingly inevitable decline, photoaging--which can lead to a cell's premature demise -- is preventable and apparently largely reversible, scientists are finding. This is good news for those who want to have young-looking skin, since photodamage, rather than intrinsic aging, causes most of the visible signs of aging, such as pigmentation changes and wrinkles.

Photoaging results from a variety of interactions between sunlight and skin, in which lights energy from the sun takes both a direct and indirect toll inside keratinocytes, fibroblasts and other skin cells. In a typical photoaging reaction, any one of a number of biological molecules inside a cell may become electronically excited after exposure to solar energy transforming it into what's known as a high-energy "singlet." A singlet may then release some of its excess energy through a series of intracellular processes, which can result in a breakup of nearby chemical bonds. In this way, cell membranes can be directly damaged within a few minutes of exposure to sunlight, especially if that light is rich in the shorter-wavelength ultraviolet (UV) range--the so-called UVB, as opposed to UVA or visible light.

Amino acids (the building blocks of proteins and enzymes) and nucleic acids (components of DNA and RNA) are the primary light-absorbing intracellular molecules damaged by ultraviolet light. In addition, sunlight can trigger a reorganization of chemical bonds -- a process called cross-linking -- within collagen and elastin fibers, and between certain proteins and DNAM, leaving them structurally and functionally crippled. Particularly susceptible to photodamage are proteins rich in the amino acid cysteine or otherwise reliant on weak, hydrogen bonds for their three-dimensional structures.

Sunlight also can have indirect damaging effects, in which energy is absorbed by oxygen to form so-called oxygen free radicals such as superoxide anions. These highly charged compounds are not solely the products of sunlight-dependent reactions; they also accumulate as normal by-products of oxygen metabolism. Neither are they exclusively harmful. "Many good, normal reactions in the body are mediated by oxygen free radicals," says Cutler.

But whether produced by sunlight-mediated reactions in the skin or by simple oxidative metabolism in the body, these "active oxygen species" appear to be primary culprits in the aging process. It's likely, Cutler says, the relatively long lifespan characteristic of human may be due to higher levels of antioxidative protective factors and, to a lesser extent, our ability to repair damaged DNA quickly.