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Alumier Skin Experts / January 20, 2016

The Science of Glycation and AGEs

When we eat food, the body breaks down carbohydrates into sugars like glucose and fructose, which are the essential fuels for cells and energy metabolism.

Glycation is the non-enzymatic reaction between sugars, such as glucose, and proteins, lipids or nucleic acids (1).  This process was first described in 1912 by Maillard, a food chemist, and its involvement in food browning during thermal processing was discovered by Hodge 50 years later (2). Since then, the involvement of glycation in various conditions has been an intensive field of research (3, 4).

Advanced glycation end products (AGEs) are proteins or lipids that have become glycated as a result of exposure to sugars. Studies on the contribution of glycation to diseases have primarily focused on its relationship to diabetes and its complications. However, even at normal glucose levels, some degree of glycation occurs and the damage caused thereby accumulates slowly over time. In addition to diabetes, AGEs have been linked to other diseases such as cataracts, Alzheimer’s, dialysis-related amyloidosis, atherosclerosis and Parkinson’s as well as physiological aging (5).

AGEs can be formed directly in the body or be exogenously ingested by eating broiled, fried or barbequed food. Reactive oxygen species (ROS) accelerate AGE formation. For healthy people with normal blood glucose levels, glycation happens gradually and slowly over a lifetime. Diet and lifestyle choices can affect glycation. In fact, the yellowing of skin often seen prematurely in smokers is a sign of glycation. Smoking reduces antioxidants in the skin so there is little antioxidant reserve to slow glycation. AGE formation is increased with age, smoking, poor diet and possibly UV exposure.

 Effects of glycation and AGEs on the skin

Over the last few years, there has been increased interest in the role of AGEs in skin aging. Glycation contributes to the visible signs of aging, including fine lines, wrinkles, discoloration, and skin thinning.

AGEs are formed intracellularly and extracellularly. Many intracellular components can be affected by glycation with detrimental effects on their function including cytoskeleton proteins, enzymes, DNA and lipids (6,7). Cytoskeletal proteins are important in providing stability of the cytoskeleton and are crucially involved in numerous cellular functions such as migration and cellular division. Intracellular glycation in the skin adversely affects keratinocyte and fibroblast function.

Glycation also negatively affects the biomechanics of the extracellular matrix (ECM) proteins like collagen and elastin. Glycated collagen is stiff and less flexible. This altered collagen also resists degradation by MMPs, therefore inhibiting its removal and replacement by newly synthesized and functional collagen (8). The appearance of glycated collagen can be first seen at the age of 20. It accumulates at a rate of about 3.7% per year reaching a 30 to 50% increase by age 80 (9, 10). The external signs of glycation are usually seen by age 35 when the body becomes less resilient and produces less collagen.

AGEs not only exert their deleterious actions directly but also indirectly through their interaction with specific cell surface receptors called receptor for AGEs (RAGE). When AGEs bind to RAGE, it initiates a cascade of signals negatively influencing cell cycle and proliferation, gene expression, inflammation and ECM protein synthesis (11). Keratinocytes, fibroblasts, dendritic cells and to a lesser extent endothelial cells and lymphocytes express RAGE (12). RAGE activation can directly induce oxidative stress and inflammation.

A 2013 study by Leiden University Medical Center and Unilever R&D identified, for the first time, a relationship between people’s blood sugar levels and their perceived facial age. The study found that people aged 50-70 with high random blood sugar levels consistently looked older than those with lower blood sugar levels. The results demonstrated that for every 1 mmol/L increase in blood sugar, the perceived age increased by five months. The study also found that the perceived facial age of diabetics, who have had long-term exposure to elevated blood sugar levels, looked older than non-diabetics. These results remained significant even after taking into account other factors known to influence facial aging such as smoking, sun exposure and body mass index (BMI) (13).

Preventing glycation and AGE formation

Since oxidation steps are involved in the formation of many AGEs, antioxidants may have antiglycating abilities (14). In addition to maintaining a healthy diet low in simple sugars and high in antioxidants, there are now skincare ingredients that specifically target glycation and AGEs.

View AlumierMD’s Featured Antioxidant Products.

 

 

References:

1) Ahmed N. Advanced glycation endproducts–role in pathology of diabetic complications. Diabetes Res Clin Pract. 2005;67:3–21
2) Lee AT, Cerami A.. The Role of Glycation in Aging. Aging and Cellular Defense Mechanisms November 1992:663;63-70.
3) Maillard LC. Action des acides amines sur les sucres: formation des melanoidines par voie methodique. C R Acad Sci (Paris) 1912;154:66–8
4) Hodge JE. Dehydrated foods, chemistry of browning reactions in model systems. J Agric Food Chem. 1953;1:928–43
5) Suji G, Sivakami S. Glucose, glycation and aging. Biogerentology 2004.5;365-73.
6) Ahmed N. Advanced glycation endproducts–role in pathology of diabetic complications. Diabetes Res Clin Pract. 2005;67:3–21
7) Baynes JW. The Maillard hypothesis on aging: time to focus on DNA. Ann N Y Acad Sci. 2002;959:360–7
8) DeGroot J, Verzijl N et al. Age-related decrease in susceptibility of human articular cartilage to matrix metalloproteinase-mediated degradation: the role of advanced glycation end products. Arthritis Rheum. 2001;44:2562–71
9) Jeanmaire C, Danoux L, Pauly G. Glycation during human dermal intrinsic and actinic ageing: an in vivo and in vitro model study. Br J Dermatol. 2001;145:10–8
10) Dunn JA, McCance DR et al. Age-dependent accumulation of N epsilon-(carboxymethyl)lysine and N epsilon-(carboxymethyl)hydroxylysine in human skin collagen. Biochemistry. 1991;30:1205–10
11) Bierhaus A, Humpert PM et al. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med (Berl) 2005;83:876–86
12) Lohwasser C, Neureiter D et al. The receptor for advanced glycation end products is highly expressed in the skin and upregulated by advanced glycation end products and tumor necrosis factor-alpha. J Invest Dermatol. 2006;126:291–9
13) Noordam R, Gunn DA. et al. High serum glucose levels are associated with a higher perceived age February 2013;35(1):189–95
8) Price DL, Rhett PM et al. Chelating activity of advanced glycation end-product inhibitors. J Biol Chem. 2001;276:48967–72

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