SKIN SCIENCE CELLULAR BIOCHEMESTRY

by Nickolaos D. Skouras, PhD.

INTRODUCTION

COENZYME-A TECHNOLOGIES INC. has applied new technology to the manufacture of a series of proprietary AntiAging Cosmeceutical products that address chemical imbalances within the body -- the effects of Cutaneous aging. The irreversible degeneration of tissue (Photoaging or Intrinsic aging) and (Nonenzymatic Glycosylation) resulting from nutritional deficiencies, environmental stress and the effects of pollution.

Skin sagging and wrinkling can be a sign of too much time spent on the beach or just a visible reminder of the relentless aging process. Cutaneous aging is a complex process affecting various layers of skin. Cutaneous aging includes the effects of gravity, expression lines, sleep lines, hormonal changes and genetic programming, and wind, smoke and chemical exposures. But mainly, there are two biologically independent aging processes that occur simultaneously which account for the major changes seen in skin over time.

The first is innate or intrinsic aging, which affects skin by slow, irreversible degeneration of tissue. The second process is extrinsic aging or photoaging, which results when skin is exposured to the elements, primarily ultraviolet radiation of the sun.

The consequences of innate aging can be observed over the entire surface of the body, including skin protected from the sun. In areas exposed to the sun, particularly the face and the back of the hands, damage from photaging is superimposed on tissue degeneration from innate aging. Thus, the most noticeable changes on facial and neck skin result from a combination of intrinsic and extrinsic aging processes.

As people age, innate or intrinsic aging changes their skin in ways that cause it to develop wrinkles. Few scientists had attributed skin aging to a single cause. But, recent research has revealed that a process long known to discolor and toughen food in storage also contributes to age-related changes in the skin.

That process is primarily the chemical attachment of the sugar glucose to skin collagen without the aid of enzymes. When enzymes attach glucose to collagen, they do so for a specific purpose and at specific places. In contrast, the nonenzymatic process adds glucose haphazardly to any of several amino group sites along any available collagen molecule.

The attachment of glucose to skin collagen triggers a series of spontaneous chemical reactions that culminate in the formation and eventual accumulation of irreversible cross-links between adjacent collagen molecules. The extensive cross-linking of collagen causes the loss of skin elasticity characteristic of aging. Therefore, "nonenzymatic glycosylation" of skin collagen is important, since it is the process that ages skin.

The steps by which glucose alters skin collagen have been understood by food chemists for decades and only recently have biologists recognized that the same steps take place in the skin. The nonenzymatic glycosylation steps between glucose and collagen may seem complicated, but they are fairly straight forward compared with many biochemical reactions:

A series of chemical reactions begin when an aldehyde group (CHO) of glucose and an ammo group (NH2) of a collagen molecule are attracted to each other. The glucose and amino group combine forming what is called a Schiff base. This combination is unstable and quickly rearranges itself into a stabler, but still reversible, substance known as an Amadori product. Long-lived collagen molecules persist in the body for years, allowing some of the Amadori products to slowly dehydrate and rearrange themselves yet again into new structures, called advanced glycosylation end-products (AGEs). AGEs are yellowish in color, and contribute to the yellowing of skin and age spots. AGEs are highly reactive, and in a final series of reactions, cross-link an adjacent collagen molecule. These AGE/collagen cross-links are irreversible and are responsible for the deep wrinkling in the dermis of the skin.

The formation of glucose-derived cross-links between long-lived collagen helps account for wrinkles seen as skin ages. Extrinsic or photoaging results from the biological effects caused by the ultraviolet (UV) radiation of the sun. The skin is always in contact with the air and oxygen, and increasingly exposed to ultraviolet radiation. As a result, the risk of photoaging induced by oxygen radicals has increased substantially. Besides those photosensitizers that are naturally in skin, skin is also increasingly exposed to photosensitizers found in air pollution, cosmetics, plant extracts, and medications. Photosensitizers transfer energy in sunlight on to ground-state oxygen to form high-energy singlet oxygen radicals, as illustrated at the right, further increasing the risk of photoaging caused by the sun. Recent research has revealed that UVA photogenerated singlet oxygen radicals cause skin damage by disrupting the natural balance found in the skin by stimulating the synthesis of collagenase, which is an enzyme that degrade collagen, without countering it with the synthesis of anti-collagenase that holds skin degradation in check. The unbalanced synthesis of collagenase and anti-collagenase caused by singlet oxygen radicals, leads to the breakdown of the extracellular matrix of collagen. This eventually causes skin to sag.

Recent research has also shown that tissue damage is done when skin is exposure to UVB radiation. Exposure to UVB radiation stimulates the release of iron and copper from skin cells, which significant increase the levels of these metals in the skin. The increased iron and copper catalyzes reactions with hydrogen peroxide found naturally in the skin, as illustrated below, to form hydroxyl radicals that damage the extracellular matrix of the skin by cross-linking collagen. This eventually causes skin to wrinkle.

Sunbathing causes photoaging of the skin, but most sun-induced skin damage that occurs over a person's life-time is the result of normal daily activities that exposures skin to ultraviolet radiation, such as working outdoors or sitting near a window. Therefore, it is important to protect the skin from sun exposure at all times. The affects of exposure to ultraviolet light are cumulative over time, and therefore it is also important to starting protecting skin from the sun as earily as possible, using more than just sunscreens.

In summary, collagen is subject to nonenzymatic glycation in which glucose chemically attaches to amino acids. Once collagen is glycated and forms AGEs, it has the potential to cross-link other collagen molecules. And once collagen is cross-linked, the cross-linking is irreversible. Early intervention is critical in inhibiting collagen cross-linking and the formation of wrinkles. UVA radiation photogenerates singlet oxygen radicals that disrupts the normal collagenase/anti-collagenase balance in the skin, causing skin to sags. UVB radiation increases the levels of iron and copper in the skin that catalyzes the formation ofhydroxyl radicals that cross-link collagen in the extracellular matrix, causing skin to wrinkle. Since the tissue damage done by ultraviolet radiation is cummulative, skin should be protect from the sun at all times and as soon as possible.

Intermolecular cross-linking of collagen is essential for viability. Collagen cross-linking is required for tensile strength in connective tissues. However, some collagen cross-linking that occurs is not beneficial. Advanced glycosylation end-product (AGE) cross-linked collagen forms insoluable aggregates, which become increasingly less susceptible to proteolytic enzymes degradation as cross- linking progresses. In aging tissue, the turnover mechanisms for collagen eventually become ineffective, resulting in the accumulation of cross-linked collagen that accelerates skin aging.

COENZYME-A TECHNOLOGIES INC. has applied new technology to the manufacture of a series of proprietary AntiAging Cosmeceutical products that address chemical imbalances within the body, the effects of (Cutaneous aging.) The irreversible degeneration of tissue (Intrinsic aging) and (Nonenzymatic Glycosylation) resulting from nutritional deficiencies, environmental stress and the effects of pollution.