Glycation: protecting against, treating, and Correcting With Topicals

Each year research teaches us more about processes and skin damage prevention and how to address them. Just as the science improves our understanding of the what, where, when, how, and why of skin aging, it also increases our ability to address skin aging. While we know that both intrinsic and extrinsic factors play a role in slowing or accelerating the aging of our skin, we have gained more knowledge about how to best correct the outward signs of aging such as fine lines and deep wrinkles.

Dermatologists and aesthetic health care providers are at the forefront of helping patients address their concerns about maturing skin. And what we know now is that it is possible to treat before the visible signs of aging appear. Why wait for wrinkles to appear if you can reduce the likelihood of their appearing and their significance?

Indeed, anti-aging efforts continue to represent an important segment of a skincare regimen. The natural process of skin aging is affected by the production and accumulation of advanced glycation end products (AGEs) in the skin, which cause the signs we associate with older skin. However, we can now prevent or reduce the formation of these AGEs through products that help maintain and create youthful skin.

At SkinCeuticals, we continue to build upon our innovative age-defying product line. Since the debut of the original anti-glycation cream, we have made great strides in advancing the capabilities of our breakthrough formulations and gone beyond being their being simply an anti-glycation cream to becoming a treatment that prevents and corrects the effects of the glycation process. Backed by science and data, our formulations produce clinically tested benefits.

— Lyndsay Zotian, PharmD, MBA
Senior Director, Medical Affairs

Glycation—what is it and how does it impact skin and appearance?

Sherry Ingraham, MD, MPH: Glycation, also known chemically as the Maillard reaction, is a multi-phase biological process in which sugars bind to proteins, like collagen, to form byproducts known as AGEs. These AGEs cause collagen to become brittle and weaken its reparative ability, degrading its overall integrity, resulting in signs of aging. AGEs provoke biomechanical and biological modifications of cellular functions and induce inflammatory pathways that contribute to skin aging. What I tell patients is: this is a normal biological process, but if we are exposed to too many exogenous factors like UV rays, smoking, and certain foods known to accelerate the formation of AGEs in skin, we further exacerbate the signs of skin aging. We will over-utilize our body’s protective mechanisms and speed up the process of AGEs formation.

What are the typical outward signs of glycation?

Dr. Ingraham: Collagen has a very long half-life and therefore is susceptible to glycation and formation of AGEs. So, in our 20s, we start to accumulate AGEs and they manifest when we’re in our mid-30s. That is when you typically start to see skin dullness, crepiness, or a sallowness. Collagen glycation contributes to wrinkles and fine line-related dermal structure change. Skin loses its soft, supple shape and the collagen becomes rigid and crunchy. When the collagen becomes rigid it manifests as wrinkles in our skin.

How do AGEs present in patients with skin of color?

Dr. Ingraham: We’d have to look at more data, but what we would see in biopsies of skin of any color is the accumulation AGEs in the skin. That would be visible via the staining of the dermis and the epidermis—mainly at the dermal-epidermal junction (DEJ)—and would show the accumulation of these AGEs that would manifest as wrinkles.

What is your experience with products that address AGEs?

Dr. Ingraham: I have been on the forefront of the science and that started with the 2009 release of the original SkinCeuticals product, A.G.E. Interrupter. Science and our knowledge of AGEs has evolved. We know a lot more not only about what causes it but how to thwart the binding or accumulation of these AGEs in our skin. We need products that are designed to inhibit the sugar-to-collagen binding in the early stages. Ingredients in a product to prevent this would include antioxidants. A.G.E. Interrupter Advanced, a breakthrough corrective cream, is formulated with wild fruit flavonoids including pomegranate fruit extract and blueberry extract which have been shown to block some of the formation of AGEs in the skin. It also includes glycyrrhetinic acid which is anti-inflammatory and antimicrobial, and used for its skin brightening effects to counter sallowness linked to the accumulation of AGEs. Its formula also has 20% more concentrated Proxylane™ compared to its original formulation. Proxylane™ was shown to stimulate the production of type VII collagen and glycosaminoglycans, which may contribute to greater skin firmness and elasticity. I am very excited about this science and its application!

SkinCeuticals is on the cutting edge in developing products and doing the research to see what ingredients specifically help collagen ward off the effects of AGEs binding, and also protect the dermis. In the dermis, where the collagen lives, is where the AGEs would bind to the collagen and exert their effects.

If we can keep that dermal matrix, with hyaluronic acids and glycosaminoglycans, nice and healthy we can help collagen be as plump, healthy, and youthful as possible. As we age and accumulate AGEs, we lose plump, healthy dermal matrix, and our fibroblasts become less functional and make less collagen. Also, the reparative mechanisms don’t work as well due to normal intrinsic aging and the environment. When AGEs accumulate, the fibroblasts become senescent and they no longer want to create that healthy collagen. But if you can use a product like A.G.E. Interrupter Advanced that supports the dermal matrix, you can keep the fibroblasts healthy and they will create more robust collagen.

When should a patient begin using these products?

Dr. Ingraham: There’s been a real paradigm shift in the way that we think. One might think, “Let’s use products that fight AGEs in patients who have accumulated AGEs,” meaning patients in their 50s and older. But what we really need to think about doing is intervening early—preventative maintenance. If patients are beginning to accumulate AGEs in their 20s then, ideally, they should start using these products in their 20s. You want to prevent the formation of the AGEs and their accumulation. One thing we know about AGEs is that once they’re there it’s very hard to eliminate them.

This is an area that needs focus and attention as we’ve learned so much more about how the skin ages through the accumulation of AGEs.

I have been suggesting these products to my younger patients, especially the newer product, A.G.E. Interrupter Advanced. I’ve been introducing the science of the accumulation of AGEs in the skin and educating my patients about it. They are very interested in the science and want to intervene early. I am addressing this by having them integrate A.G.E. Interrupter Advanced into their regimen now. Typically, I tell a patient in their 20s that we should create an environmental shield by using a robust antioxidant in the morning, applying a broad-spectrum sunscreen over that, and then in the evening stimulate, maintain, and protect the collagen. We do that by having a product such as A.G.E. Interrupter Advanced applied in the evening either as a monotherapy or with a retinoid, depending on the patient. If a patient has been using a retinoid as a core in their regimen, and an antioxidant in the morning, as I do, I put my antioxidant on in the morning, put my A.G.E. Interrupter Advanced on top, and layer over my sunscreen. In the evening, I put on my retinoid, my A.G.E. Interrupter Advanced on top of that.

Is this product suitable for all your patients?

Dr. Ingraham: I have found it is well tolerated and is actually being utilized by patients of all skin types and skin tones.

It’s a very, very unique product. You can get great collagen stimulation and great dermal matrix support because of the Proxylane™ it contains. It’s a very well tolerated product and can be introduced to your patient’s established regimen.

How quickly do your patients see improvement with A.G.E. Interrupter Advanced?

Dr. Ingraham: Patients typically tell me they notice results within about 12 weeks. They’ll say that their skin feels firmer and they do have softening of fine lines and wrinkles.