The Effect of Glycation on Ageing.

Ingrid Bergman once said, ‘Getting old is like climbing a mountain; you get a little out of breath, but the view is much better!”. No matter how you define ageing, it is at the end of the day (no pun intended!) a progressive loss of the efficacy of biochemical and physiological processes that occur until one dies. There are many theories to explain what happens whenever we age. Many theories have been advanced to explain ageing. In this article, I want to focus on two main issues:

1)??????Exposure to sugars, and how it affects or modifies proteins and lipids

2)??????Advanced glycation end products (AGEs) and their harmful effects on the body and skin

Glycation and Aging.

Numerous publications have demonstrated advanced glycation end products (AGEs) being involved in the acceleration of the aging process. The progressive accumulation of these AGEs in the body is a hallmark of the aging process in humans, animals, and other organisms. Besides external stimuli, that would include sunlight, UV radiation, chemicals, pollutants, and smoking, exogenous AGEs in dietary foods also trigger organ dysfunction and tissue aging. Endogenous processes that trigger the aging process include reduced cell proliferation, impaired immune functioning, excessive free radical production, shortening of the telomere, nuclear/mitochondrial gene mutation, and cellular senescence. Oxidative stress, more specifically oxidative damage to proteins, plays an important role in the mechanism by which AGEs form and accumulate, and has been implicated as a key factor in the progression of various diseases, including chronic diseases, especially Alzheimer’s disease, and aging.

Glycation and the skin

Although most research into the changes in skin with age focus on the unwelcome aesthetic aspects of the aging skin, skin deterioration with age is more than a merely cosmetic problem. The characteristic features of aging skin include wrinkles, dryness of the skin, reduced skin thickness, loss of elasticity, dermal and epidermal atrophy, reduced rate of epidermal cell proliferation and cellular senescence. In recent years, many scientific studies have revealed that Advanced Glycation End products (AGEs) are also among the crucial contributory factors of skin aging. Accumulation of AGEs in the skin has been observed both in diabetes and during chronological aging. Proteins with a slow turnover rate, such as collagen I and IV, as well as long- lived proteins, such as fibronectin, are primary targets of glycation reaction in the skin. Moreover, excessive deposition of AGEs in sun-exposed skin areas suggests that solar radiation, especially UV radiation, may play an important role in the formation of AGEs. Receptors for AGEs are generally expressed in the epidermis and dermis, and it has been observed that the expression is higher in the sun-exposed areas of the skin as compared to sun-protected areas. Most commonly found AGEs in the skin include carboxymethyl-lysine, carboxyethyl- lysine, pentosidine, methylglyoxal and glyoxal, glucosepane and fructose-lysine. The degenerative changes that occur in the aging skin are increasingly understood at both the molecular and cellular level, facilitating a deeper understanding of the structural and functional deterioration that these changes produce.

The chemistry of Glycation?

?·????????Glycation is a general term describing the addition of a carbohydrate to another molecule, in this instance a protein, lipid, or DNA.

·????????Typical sugars that participate in glycation are glucose, fructose, and their derivatives.

·????????Glycation may occur either enzymatically or nonenzymatically.

·????????The common term for enzymatic glycation is glycosylation

·????????Nonenzymatic glycation, is commonly used in reference to reducing sugars with proteins or by the reaction of glucose with lysine residues in protein to form a ketoamine (Amadori) product (Figure 1).

·????????Glucation, fructation, ribation, etc. are used in reference to glycation by specific sugars.

Louis-Camille Maillard

The Amadori products above undergo a series of chemical reactions that lead to the formation of advanced glycation end products (AGEs). This process was first noticed by Louis-Camille Maillard in 1912. Maillard was a French physician and chemist, who made important contributions to the study of kidney disorders, but we remember him in this article for the “Maillard reaction”, the chemical reaction by which amino acids and sugars react in foods via contact with fats, giving a browned, flavorful surface to everything from bread and seared steaks to toasted marshmallows. Technically, because we evolved as hunter gatherers used to eating raw meat there are no enzymes to remove glycated products from the human body. Some would say the glycation process causes the accumulation of metabolic waste and this promotes ageing. Glycation is responsible for many vascular complications in diabetes mellitus and is implicated in skin aging Louis- Camille Maillard

How do we prevent glycation?

The most obvious way is to search for an inhibitor of AGE formation, which could prevent the glycation process. This has led to several natural products being identified, including medical herbs, dietary plants, and phytocompounds inhibit protein glycation. These natural products have high antioxidant capacity and may hold the key to prevent glycation and AGE formation. Their anti-AGE activity may be one mechanism of their beneficial actions on human health. Since autofluorescence is an intrinsic property of AGEs, measurement of skin fluorescence is an effective method of detecting AGE deposition in the skin. Inhibition of AGE formation – Pimagedine, also known as aminoguanidine, is an investigational drug for the treatment of diabetic nephropathy that is no longer under development as a drug. It is known to prevent AGE formation by sequestering early glycation products, such as carbonyl intermediates. However, it has many side effects and apparently has no little on advanced glycation products. Another such compound is pyridoxamine, one form of Vit B6, which is used to prevent or treat low levels of vitamin B6 in people who do not get enough of the vitamin from their diets. It has been shown to have good results in phase II clinical trials involving patients with diabetic neuropathy. This compound is known to inhibit advanced glycation products.

Sources: https://www.isdin.com/en-US/blog/skincare/moisturizers/whats-glycation-and-how-to-fight-it

Gkogkolou, P., B?hm, M. Advanced glycation end products: Key players in skin aging? In?Dermatoendocrinology?(2012); 4(3): 259-270.

Data on file, ISDIN Corp, Morristown, NJ 07960

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