Glycation is one of the basic root causes of endogeneous (intrinsic) skin ageing and a very challenging one or almost impossible one to reverse. Glycation is an ageing reaction which begins in early life, developing clinical symptoms at around 30, and progressively accumulates in tissues and skin due to the glycated collagens that are difficult to be decomposed. Glycation occurs naturally in the body when sugars react with proteins and lipids to form advanced glycation end products (AGEs). AGEs can be exogenously ingested (through food consumption), inhaled via tobacco or endogenously produced and formed both intracellularly and extracellularly. AGE modifications lead to dermal stiffening, diminished contractile capacity of dermal fibroblasts, lack of elasticity in the connective tissues, contribute to hyperpigmentation and a yellowish skin appearance. The formation of AGEs is amplified through exogenous factors, e.g., ultraviolet radiation. 

AGEs cause changes in the skin through 3 processes:

1. AGEs interact with specific cell receptors, altering the levels of soluble signaling molecules, such as cytokines, hormones, and free radicals.
2. 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. This causes synthetic disorders of collagen in skin tissues. 
3. AGEs alter the physical and biological properties of the original extracellular matrix proteins, such as collagen. 

Many cells have AGEs receptors on the surface, such as macrophages, mesangial cells, fibroblasts, and endothelial cells, through which their function can be affected. They induce oxidative stress and trigger inflammatory pathways by forming crosslinks, altering protein structure, or by binding to AGEs receptors. AGEs cause cellular dysfunction through the modification of intracellular molecules and accumulate in tissues with ageing. This causes the skin and connective tissue to harden and lose their ability to regenerate healthy cells. They cause damage to extracellular proteins like collagen and elastin fibers, which are crucial for maintaining skin structure and firmness. This damage leads to the breakdown of these fibers. AGEs can also affect intracellular proteins like vimentin. AGEs can act as a catalytic site for free radical formation, exacerbate intracellular oxidative stress, and increase ROS production through a variety of mechanisms, reducing glutathione (skin's own anti-oxidant) storage, and activation of protein kinase C, etc., to accelerate the production and accumulation of AGEs. 

One study published in the Journal of Investigative Dermatology found that levels of AGEs were higher in the skin of older individuals compared to younger ones. The study also showed that there was a correlation between the level of AGEs and the severity of skin ageing. This suggests that inhibiting the production or accumulation of AGEs in the skin is a potential target for anti-ageing interventions or skin ageing management.

AGEs are complex and heterogeneous, more than a dozen AGEs have been detected (however not all) in tissues and can be divided into three categories according to their biochemical properties. 
​AGEs are formed through four pathways:

1. the Maillard reaction (non enzymatic reaction between amino groups of proteins and reducing sugars, binding sugars to proteins)
2. sugars auto-oxidation pathway (metal-catalyzed auto-oxidation of glucose or Wolff pathway) 
3. lipid peroxidation pathway (acetyl alcohol pathway)
4. polyols pathway (glucose is converted into fructose via the polyol pathway, which accelerates the production of AGEs)

GLYCATION INHIBITION IS KEY 
AGEs can be crosslinked through side chains to form a substance of very high molecular weight, which is not easily degraded. The consequences from skin glycation are irreversible. This makes prevention or inhibition of the process the best potential strategy to maintain skin health and ageing skin management. One way to do this is by altering the diet to reduce the intake of sugars and carbohydrates, which are known to contribute to glycation. Several studies have found that reducing sugar intake can result in significant improvements in skin health, including reducing wrinkles and improving skin texture. 

AGE inhibitors
Another potential strategy is the use of topical agents that inhibit the formation or accumulation of AGEs in the skin. One study published in the Journal of Cosmetic Science found that a cream containing carnosine, a peptide that inhibits glycation, improved skin elasticity and reduced the appearance of wrinkles in individuals with ageing skin. Skincare containing NAHP or Acetyl Hydroxyproline inhibits the formation of AGEs significantly (in vitro), most likely through a mechanism where NAHP competes with the proteins for the sugar. Finally, NAHP sacrifices itself in place of the proteins and gets (at least partially) glycated. NAHP also prevents loss of cellular contractile forces in a glycated in vitro dermis model and counteracts the diminished cell-matrix interaction that is caused by glyoxal-induced AGE formation.

​Anti-Oxidants
Moreover, I would suggest to combine those ingredients with an ingredient like Licochalcone A. Numerous high ranked publications support that Licochalcone A protects cells from oxidative stress mediated by e.g. UV and HEVIS (blue light) induced reactive oxidative species (ROS). Due to the activation and nuclear translocation of the transcription factor NrF2, the expression of anti-inflammatory, antioxidant and detoxifying enzymes are induced. These enzymes protect the skin cells (like keratinocytes and fibroblasts) from ROS-induced damage, like lipid peroxidation and DNA as well as protein damage. If Licochalcone A is combined with L-Ascorbic Acid, (the most active form of Vitamin C), it supporting skin's own collagen production, provides superior biological cell protection amongst other relevant benefits. My absolute favourite product is Eucerin Hyaluron-Filler Vitamin C Booster which I use daily as a serum in my morning routine.

GLYCATION AND SKIN HEALTH

Acne
In addition to its role in ageing, glycation in the skin has also been linked to a range of skin health problems. One study published in the Journal of Cosmetic Dermatology found that the level of AGEs in the skin was significantly higher in individuals with acne than in those without acne. The study also showed that treating acne with a topical antibiotic significantly reduced the levels of AGEs in the skin.

Atopic Dermatitis
Another study published in the Journal of Investigative Dermatology found that individuals with atopic dermatitis had higher levels of AGEs in their skin than healthy individuals. This suggests that glycation may play a role in the development of inflammatory skin conditions.

Diabetes + Woundhealing
The correlation between high sugar levels and skin ageing can be seen in diabetic patients, where one-third of this population has skin complications. A prominent feature of ageing human skin is the fragmentation of collagen fibers, which severely damages the structural integrity and mechanical properties of the skin. Elevated levels of MMP-1 and MMP-2 and higher crosslinked collagen in the dermis of diabetic skin lead to the accumulation of fragmented and crosslinked collagen, thereby impairing the structural integrity and mechanical properties of dermal collagen in diabetes. Collagen crosslinking makes it impossible for them to easily repair, resulting in reduced skin elasticity and wrinkles. Keratinocytes and fibroblasts are the main cells involved in wound healing, but due to the high glucose (HG) microenvironment in diabetics, the functional state of these cells is impaired, thereby accelerating cellular senescence (programmed cell death).

Conclusion
We can't completely stop the glycation process, therefore it's important that we inhibit it from a young age onwards, hence monitor the sugar intake of our children, use daily SPF and invest in good dermo-cosmetic products containing ingredients like NAHP and powerful anti-oxidants like L-Ascorbid Acid (Vitamin C is needed for the production of collagen) and Licochalcone A (also anti-inflammatory). Preventing signs of ageing, specifically caused by glycation is most effective. If your skin shows (advanced) signs of ageing, you can get visible improvement using skin component (hyaluron, collagen and elastin) bio-stimulating ingredients like Retinol, Bakuchiol, Arctiin, Creatine or Glycine Saponin. Consult your dermatologist if you wish to improve your skin's appearance or skin health issues.

Take care

Special thanks: Ph.D. dr Julia M. Weise Manager Biological Testing & Dorothea Schweiger Lab Manager Facial Skin Biology Beiersdorf HQ Hamburg

Psoriasis occurs in many different forms and levels of severity. The first signs may appear between the age of 15 and 35 and 75% of patients are diagnosed before the age of 46 according to the World Health Organisation. As there is no cure for the disease, the highest prevalence is seen in a more mature age group age 50-69. Many of the treatments which are part of the standard treatment guidelines for psoriasis cause as a side effect premature ageing skin. For example PUVA, next to being an effective treatment, does cause (severe) photo-damage. Many patients will undergo such treatments on and off or continuously throughout their life.

Although the primary goal of dermatology is to improve the functional attributes of the skin (health) and lessen the tremendous burden psoriasis may cause, ultimately one aims to improve the skin's physical attributes (appearance).

Ageing skin is a biological degenerative process which influences the activity of collagen and hyaluronic acid producing cells (mainly fibroblasts) and leads to a decrease of skin components like collagen, hyaluron and functional elastin. Effective anti-aging skincare can support the protection of those cells and skin components (anti-oxidants and SPF) and thus slow down the fastened degenerative process. Some active ingredients (for example biologically active Glycine Saponin and Arctiin) have proven to effectively stimulate fibroblasts in the production of collagen and hyaluronic acid and thus replenish dermal components. Loss of those components and photo-damage eventually lead to visible signs of ageing.

Although ageing skin is natural, premature ageing skin isn't necessary. Most patients will probably already use a moisturising facial skincare product. It makes sense to recommend anti-ageing skincare instead to be used in conjunction with treatments which as a side effect cause premature ageing skin, particularly for exposed areas like the face. As psoriasis oftentimes doesn't occur in the face (except in the hairline), anti-ageing skincare will pose a low to no risk to aggravate facial skin and there are anti-ageing skincare products available which have proven to be suitable for psoriasis patients. 

Take care.