What is glycation? What are A.G.E.s? And what about that “safe” sunless tan?
Remember: broken or badly modified proteins can’t do their job.
Fibroblasts are the main cells in the dermis, and they specialize in producing two types of proteins, collagen and elastin, which are a major part of the extra-cellular matrix. When you are choosing ingredients for skin care it’s important to think not just of increasing the synthesis of skin proteins (what everybody talks about) but also of preserving their structure intact. Changes in protein structure are definitely going to change how the skin functions and how it looks, and it’s never for the better!
One thing we want to do is to prevent glycation, the chemical attachment of sugars, without the participation of enzymes, to the amino acids that make up a protein.These sugars will affect amino acid charges and how the proteins fold in space, characteristics that are essential to how the protein behaves. You definitely don’t want that!
In contrast to glycation, glycosylation is the enzyme-mediated ATP-dependent attachment of sugars to protein or lipid. Glycosylation occurs at defined sites on the target molecule. It is a common form of post-translational modification of proteins and is required for the functioning of the mature protein.
Glycosylation (programmed) good, glycation (disordered) bad.
Advanced glycation end products (AGEs) are proteins or lipids that become modified as a result of exposure to sugars. Nucleic acids can also get modified in this way, also bad news. AGEs are an indication of aging in general and the development of many degenerative diseases; they are also involved in skin aging. A distinctive feature of aging at the molecular level is the gradual accumulation of non-enzymatically modified proteins, i.e., glycation, which produces skin problems, such as wrinkles, pigmentation, and yellowing of the skin color
In the lab, AGE modifications of proteins have been shown to be toxic, immunogenic, and capable of triggering cellular injury. How? AGEs interact with their specific cell receptors, altering the levels of soluble signaling molecules, such as cytokines, hormones, and free radicals. In the process of non-enzymatic glycation reaction, a large number of reactive oxygen radicals are released, creating a state of oxidative stress, leading to a significantly reduced level of glutathione, Vitamin C, and Vitamin E in the body. AGEs also alter the physical and biological properties of the original extracellular matrix proteins, such as collagen. Keratinocytes and fibroblasts are the main cells involved in wound healing, but in diabetic patients, because of the resulting high glucose concentration, cells don’t work as well, accelerating cellular senescence.
Skin autofluorescence (SAF) has been shown to be a biomarker of cumulative skin AGEs, and measuring facial fluorescence intensity allows for an assessment of the skin glycation index.
That “safe”, sunless tanning
What is sun-less tanning? It’s based on the formation of melanin-looking skin pigments, ‘melanoidins’, from glycation of epidermal amino acid/protein components by reactive sugars like dihydroxyacetone (DHA). Sunless tan causes stress to the skin; over time, glycation causes skin AGEs to accumulate, resulting in wrinkles, loss of elasticity, dullness, and decreased function of skin, which is one of the main mechanisms of skin aging.
Are AGES “forever”?
No, the skin is alive, and it will deal with them somehow But AGES are hard to get rid of because they are not the original protein the body is used to. AGEs can be internalized by fibroblasts through receptor-mediated endocytosis and further degraded by lysosomal proteases or proteasomes. If collagen is severely crosslinked, the protease collagenase can’t degrade the modified collagen, causing AGEs to accumulate in the dermis.
Figure (from Zheng W et al., 2022). The effects of UV exposure combined with AGEs on the skin. A dotted line with an arrow indicates an induced effect; a dotted line with a diamond shape indicates a suppressive effect. AGEs in the skin are endogenously generated or exogenously ingested, including CML, CEL, pentosidine, and glucosepane, etc. Collagen is more likely to be glycated due to the slow turnover rate. On the one hand, AGEs act directly on cells, leading to a decrease in cell function by activating inflammatory signaling pathways and oxidative stress through cell surface receptors, as well as by modifying cell membranes and intracellular molecules, resulting in skin problems, such as dullness, pigmentation, and wrinkles. On the other hand, AGEs crosslink with collagen and elastin in ECM and promote the secretion of melanin, causing skin problems, such as macula and loss of elasticity. In addition, UV exposure can exacerbate skin glycation by promoting the generation of AGEs, exacerbate oxidative stress, and reduce epidermal GLO-2 production, leading to the accumulation of AGEs. AGEs can be degraded by proteases through receptor-mediated fibroblast endocytosis; the glyoxalase system can detoxify the reactive precursors of AGEs; sRAGE can competitively bind to AGEs with RAGE.
In short, how to fight glycation?
1) Control diabetes
2) Avoid sun-less, “chemical” tans
3) Take care of your skin proteins (trust Skin Actives for this)
4) Avoid real sun tans.
Fighting glycation with topical skin care
Have a look at our collagen serums, all of them contain carnosine and other actives that will help prevent glycation. Carnosine is a naturally occurring dipeptide (beta-alanyl-l-histidine), which slows down the formation of protein carbonyl groups and has the ability to chelate transition metal ions, and reduce sugar-induced crosslinking
Ingredients: Water, Seakelp (Lactobacillus/Kelp Ferment Filtrate) Bioferment, Glycerin, Sodium PCA, Magnesium Ascorbyl Phosphate (Vitamin C), Hydrolyzed Collagen, Sodium Hyaluronate (Hyaluronic Acid), Boswellia Serrata Extract, Centella Asiatica (Gotu Kola) Extract, Carnosine, N-Acetyl-D-Glucosamine, Niacinamide, Betulinic Acid, Camellia Sinensis (Green Tea) Epigallocatechin Gallate, Glutathione, sh-Polypeptide-2, sh-Oligopeptide-1 (Epidermal Growth Factor), Citric Acid, Phenoxyethanol (and) Caprylyl Glycol (and) Sorbic Acid.
Other options: Some natural compounds (phenols, oligosaccharides and polysaccharides, carotenoids like β-carotene, and unsaturated fatty acids) have the potential to combat the formation and accumulation of AGEs. Other ingredients that may help: rosmarinic acid, resveratrol, quercetin, rutin, and the hydrophobic extract of Dunaliella salina, rich in colorless carotene phytoene and phytofluene, has anti-glycation and anti-inflammatory activity. Black galangal extract inhibits the formation of fluorescent AGEs. Pomegranate fruit extract, its phenolic constituents (punicalagin, ellagic acid, and gallic acid), all have effective anti-glycation activities. Pyridoxamine, one of the natural forms of vitamin B6, helps by metal-ion chelation and blocking oxidative degradation of Amadori intermediates.
DIY
Add this powder to your favorite water-based concoction!
https://skinactives.com/carnosine-powder/
Carnosine helps to reduce the appearance of wrinkles and improves skin tone and texture. Having carnosine in your skin care can combat signs of aging by preventing cross-linking of collagen and other proteins which can cause a loss of elasticity. This skin care ingredient emulates natural carnosine which is found in your body and doubles as an added building block to protect your skin.
References
Zheng W, Li H, Go Y, Chan XHF, Huang Q, Wu J. Research Advances on the Damage Mechanism of Skin Glycation and Related Inhibitors. Nutrients. 2022 Nov 1;14(21):4588. doi: 10.3390/nu14214588. PMID: 36364850; PMCID: PMC9655929.
Claims on this page have not been evaluated by the FDA and are not intended to diagnose, cure, treat or prevent any disease.