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“Protein Crosslinks” As A Cause Of Aging
 

Have you heard that sugar ages you? I know you don’t want to believe it—but the evidence is there. Sugar is the energy that our cells need in order to function, however, it can damage vital proteins by causing them to crosslink, which means they stick to themselves and other proteins. Protein crosslinks naturally occur in our body. This is a process that we are all very familiar with, although not in relation to aging. When we bake bread, the browning of the crust is due to protein crosslinking. Caramelizing sugar, browning a turkey and baking cookies is all the same process that leads to crosslinked proteins. First, I will explain a little basic chemistry and then I will discuss how this knowledge can help you better understand skin aging and the claims that certain skincare products make.


Basic chemistry


The Maillard reaction was first described by a food chemist named Louis Camille Maillard in 1910, but scientists did not recognize the importance of this reaction until the 1980s. This reaction is not the only way that proteins are crosslinked, but it is the most understood. In the Maillard reaction, heat and other conditions cause a sugar molecule’s structure to open and glue itself (glycate) to a protein molecule. This sugar+protein molecule is called a Schiff base.



The Schiff base is unstable and rapidly degrades to a more stable structure called an Amadori product. Amadori products can cause proteins to crosslink each other and that is where the problem arises. These crosslinked proteins are called Advanced Glycation Endproducts, or AGEs.



Glycation and disease


Much of the research on glycation has focused on how diabetes affects the body. Diabetics have increased sugar in their blood, which leads to protein damage that manifests as coronary artery disease, poor circulation and vision problems. This is why diabetes treatment focuses on lowering blood sugar levels with insulin and other medications. When doctors check how well a patient is doing at keeping their blood sugar down, they order a test called Hemoglobin A1c or HBA1c. This test measures the levels of glycated hemoglobin, which is a Amadori byproduct of sugar binding the hemoglobin in blood.


AGE crosslinks bind vital proteins such as elastin, which is needed to give skin and organs elasticity and the ability to bounce back. When the AGE crosslinks damage elastin, the arteries lose elasticity, which is one cause of high blood pressure. The ability of the heart to pump blood is also impaired. The AGE Endproducts can damage the nerves, kidney and many other organs as well. They also damage many types of proteins, including collagen. It is important to know that sugars are not the only cause of glycation. Fats such as triglycerides also lead to AGEs. For this reason, healthy diets include low-fat and low-carbohydrate (sugar) diets.


A little bit more science


Free radicals cause the AGE precursors to turn more rapidly into the dangerous AGEs. Many have touted antioxidants as a method of preventing AGEs. Although antioxidants are beneficial for many reasons, they do not seem helpful in preventing the glycation process. This is because once the Schiffs base is formed, it is unstable and it has to turn into something else to become stable again. Using antioxidants may be able to block one pathway, but the Schiff base goes down another pathway that still results in harmful crosslinks. This is described in Chapter 9 of Ending Aging.


Glycation and skin aging


Two main proteins play a major role in skin’s appearance: Collagen and elastin. These are found in the dermal layer of the skin. Collagen gives skin its strength, and loss of collagen makes older skin fragile and thin. Glycosylated collagen is believed to play a role in aged skin’s appearance.



When glycation occurs, sugar molecules attach to collagen fibers and begin a series of chemical reactions. The end-result of these reactions is the formation of “crosslinks” that bind collagen fibers to each other—in turn making the skin stiffer. This chemical reaction is similar to tanning a leather hide.


Elastin gives the skin the ability to resist stretching. Sun-exposed skin sags and loses its ability to bounce back. When we look at sun-exposed skin under a microscope, we see that the elastin is abnormally clumped together and nonfunctional. Recent research has found that these clumps are likely caused by glycation, since the clumped elastin is stiff and has lost its springiness. This is what’s happening inside sagging skin.


A 2007 study in the British Journal of Dermatology found that sugar's effects on the skin begin to show at about age 35 and become more pronounced as we age. And it's not just the obvious sugary culprits like soda and candy that cause damage; other foods with a high glycemic index, like white bread, pasta and potatoes also cause the formation of AGEs, because they are quickly converted to sugar in the bloodstream. To make matters worse, AGEs also make the skin more susceptible to sun damage, which in turn accelerates the glycation process.


It's hard to resist the lure of chips, cookies and French fries, but cutting down on sugary and starchy foods is the first step toward repairing AGE damage and preventing further glycation from occurring. The GI Database, maintained by the University of Sydney in Australia, is a handy tool that helps you determine the glycemic index of your food and includes many well-known brands and products. (Turn tonight's dinner into tomorrow's great skin.)


Does skincare work?


At this point in time, it seems diet is the main way to control AGE damage within the skin, but there has been talk about the effects of topical skincare products.


  1. Antioxidants were once thought to help prevent glycation, but they merely cause the glycation process to go down a different path—which does not prevent skin aging. Antioxidants are good for your skin, but they don’t seem to reduce glycation.
  2. Dr. Brandt offers products that claim to stop AGEs. It is unknown if these penetrate, and I have not seen scientific proof that they work—yet.
  3. Sunscreen is still the best way to prevent visible signs of aging, and you reap maximum prevention when you eat less sugar in addition to using SPF every day.

We hope that you enjoyed the third installment in our series about “The 7 causes of Aging.” Stay tuned for next week when we’ll discuss “Junk accumulating inside cells” as a cause of aging.



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