Prevent Glycation-Induced Skin Aging with Topical Nutrients
By Gary Goldfaden, MD, and Robert Goldfaden

One of the most visible signs of premature aging occurs in the skin, where once firm, healthy collagen strands give way to wrinkling, dryness, and looseness. While external factors such as sun exposure can accelerate extrinsic skin aging, scientific evidence points to another culprit: glucose-driven intrinsic aging. Glucose is a vital cellular fuel. However, based on the accelerated rate of aging seen in diabetics,1 chronic glucose exposure has long been known to affect how the body ages by a process called glycation.

How AGEs Are Formed
The same browning reaction that occurs when you cook meat at high heat takes place at a slower rate to long-lived tissue proteins such as collagen in our bodies. When the proteins in meat are exposed to heat and carbohydrates in the absence of moisture, they cause it to turn brown in a chemical process called the Maillard reaction. Similarly, in the human body, once sugars enter the circulation, they attach themselves to the amino groups of tissue proteins such as collagen to slowly rearrange their youthful structure into the main culprits of damage, called advanced glycation end products (AGEs). AGE molecules are particularly destructive since they can undergo extensive cross-linking with other proteins to form strong chemical bridges. As a result, once healthy collagen fibers lose their elasticity, becoming rigid, more brittle, and prone to breakage. Strong scientific evidence also indicates that glycation reactions are promoted by oxidative stress and lead to the production of reactive oxygen species in the skin.

This assault on the skin’s structural support system contributes to the aging of tissues and, when accelerated by hyperglycemia, to the gradual development of diabetic complications. Not surprisingly, collagen abnormalities with aging and in diabetes share similar roots and have widespread consequences for the skin, such as thinning, discoloration, loss of elasticity, and tendency to rashes and infections.

Skin Structure
Before we see how the skin is affected by glycation, let’s briefly review its structure. In order to provide a solid support to external influences, our skin consists of two layers: an outer layer called the epidermis and the layer below that called the dermis. New cells generated by the dermis are continually being pushed upwards to replace old cells, providing essential support to the epidermis. The dermis itself consists mainly of an extracellular matrix comprised of proteins, especially collagen fibers, elastin, and various glycoproteins, all of which are synthesized by major skin cells called fibroblasts. It also contains hyaluronic acid, which belongs to a class of large, sugar-like compounds known as glycosaminoglycans (GAGs). Hyaluronic acid is capable of holding up to 1,000 times its own weight in water and helps to bind water in the skin, providing essential support for the collagen framework as well as protecting the skin’s elasticity.

There are several different types of collagen in the body. The major structural components in the skin are collagen types I and III, which account for over 70% and 15%, respectively of its dry weight and provide the dermis with tensile strength and stability. Another type of collagen—type IV—is responsible for the mechanical stability of the skin’s scaffolding, known as the basement membrane, which lies in the inner lining of the epidermis where it connects to the dermis.

Glycation and Aging Skin
Healthy collagen metabolism is a complex process that requires balanced synthesis and degradation to maintain the firm appearance of young, healthy skin. As skin ages, however, it becomes especially vulnerable to glycation, because collagen comprises up to one-third of the body’s proteins and has a slow turnover rate. Once glycated, collagen fibers have reduced regenerative ability, leading to the wrinkles, creping, and sagging that characterize skin aging.

A number of studies show that glycation of collagen increases with age when cells are exposed to not only high levels of glucose, but also to normal levels for a long enough time. A specific receptor for AGEs, called RAGE, has even been found to be expressed in skin fibroblasts that are responsible for synthesizing collagen, which further compromises skin integrity.

Glycation not only impairs the assembly of collagen macromolecules, but it keeps type IV collagen molecules from forming a normal network-like structure. It also degrades collagen types I and III. After the age of 35, women naturally suffer a decline in collagen type IV, further exacerbating these changes.

Laboratory research shows that once formed, AGEs can be self-perpetuating—directly inducing the cross-linking of collagen even in the absence of glucose. Glycation also induces fibroblast apoptosis (cell death), which creates a state of cellular senescence that has been shown to switch fibroblasts from a matrix-producing to a matrix-degrading state. In this state, the secretion of collagen-degrading enzymes, called matrix metalloproteinases (MMPs), increases and levels of their inhibitors decline.

In fact, glycation directly increases the release of MMP-1, which preferentially breaks down collagen. While these assaults on the skin occur internally, external sources of oxidative stress can also aggravate skin aging. In particular, sun exposure increases levels of MMP-1 in the skin.

Protein glycation and AGE formation are accompanied by increased free radical activity in skin collagen which accelerates skin aging. All of these changes create an environment within the skin that favors degradation of collagen over its synthesis, compromising the integrity and regeneration of skin tissue.

Powerful Nutrients That Fight Glycation
While the effects of glycation may seem unrelenting and unavoidable, a number of topical nutrients have been scientifically shown to protect against the destructive effects of glycation and help boost the skin’s healing capacity.

What You Need to Know About Glycation-Induced Aging:
In addition to environmental factors, intrinsic factors such as glycation-induced aging threaten to diminish the skin’s youthful appearance.
Advanced glycation end products (AGEs) are formed when sugars react with proteins such as collagen, an essential component of healthy skin.
AGEs threaten healthy skin by reducing the collagen’s regenerative ability and increasing collagen breakdown. The result is wrinkling, creping, and sagging skin.
Topical nutrients such as blueberries, pomegranate, vitamin C, tea blends, and hyaluronic acid can help protect against the damaging effects of glycation and oxidative stress on the skin.
The result is improved skin texture, decreased wrinkles, more elasticity, and protection against ultraviolet-induced damage.
Given the prevalence of AGE-inducing factorswe encounter every day, such as dietary sugars and foods cooked at high temperatures, comprehensive topical protection against damaging glycation is a crucial factor in maintaining a youthful appearance.