What is the Importance of AGEs in Skin Aging?

We now know that skin aging is not just about age. Increasing scientific evidence reveals that AGEs, or "Advanced Glycation End-products," are at the heart of this process, accumulating in the skin with age and causing serious damage. So, what are AGEs, how do they age our skin, and how can we combat these harmful compounds?

What Are AGEs and How Do They Damage the Skin?
AGEs are harmful compounds formed by the chemical cross-linking of proteins, lipids, or nucleic acids with reducing sugars. This process occurs through a chemical mechanism known as the Maillard reaction. This reaction, which we call "sugaring" within the body, accumulates in skin cells and damages skin tissue over time.

In addition to aging, external factors such as sun exposure, air pollution, and smoking also accelerate the formation of AGEs. Structural proteins in the skin's connective tissue, such as fibrillin-1 and vimentin, become targets of AGEs, leading to loss of elasticity. The result? Sagging, lifeless, and wrinkled skin.

AGEs Don't Just Aging the Skin
The damage caused by AGEs isn't limited to mechanical deterioration. They also activate RAGE receptors on the cell surface, leading to oxidative stress and inflammation in the skin. Furthermore, they can increase melanin production in melanocytes, causing unwanted skin pigmentation, or blemishes. Therefore, AGEs should be considered not only in aging skin but also in individuals experiencing blemishes and loss of elasticity at a young age.

What is the Way to Combat AGEs?
Two key strategies stand out for combating AGEs:

1. Preventing AGE Formation
AGE formation is directly linked to high blood sugar levels and diets high in sugar. Therefore, a low-glycemic index diet is important for reducing glycation stress. However, this measure alone is not sufficient.

2. Clearing Formed AGEs
It's critical not only to prevent AGEs before they form, but also to remove them from the body. This is where cellular cleansing mechanisms come into play: lysosomal, proteasomal, and especially autophagic pathways.

Autophagy: The Cellular Garbage Collector
Autophagy is a natural recycling system that eliminates damaged proteins and organelles within the cell. Research shows that autophagy is weakened in aging skin, increasing the accumulation of AGEs.

New studies reveal that certain natural and synthetic compounds can reduce AGEs by activating autophagy. Substances such as Nymphaea alba flower extract, sucrose dilaurate, and circular RNA are particularly promising.

NdCAT: A Next-Generation Anti-AGE Agent?
The recently developed N-dichloroacetyltryptamine (NdCAT) is attracting attention as an innovative molecule capable of bidirectionally influencing AGE formation. NdCAT, a powerful antioxidant, suppresses AGE formation and stimulates autophagy, enabling the removal of existing AGEs from cells.

In laboratory and cell culture experiments, NdCAT has been observed to reduce AGE levels and inflammatory markers. In an ex vivo human skin model and a clinical study with 21 female volunteers, NdCAT not only reduced AGE accumulation in the skin but also had positive effects on elasticity, melanin levels, and moisture balance.

What Did the Clinical Study Results Show?
In a 4-week clinical study, participants who used a care product containing NdCAT twice daily reported:

A significant decrease in skin AGE levels,

An increase in elasticity,

An improvement in moisture,

A balance was achieved in melanin and erythema indices.

Furthermore, immunofluorescence analyses performed on corneocyte samples revealed a significant decrease in the surface presence of AGEs.

Conclusion: Why is it important to approach skin aging from an AGE perspective?
Today, simply supporting collagen production isn't enough in anti-aging skincare products. Clearing the skin of accumulated harmful molecules—especially AGEs—is a key step in regaining a youthful glow.

Thanks to new-generation compounds like NdCAT, a preventative and restorative approach to combating AGEs is becoming possible. It's anticipated that AGE-targeted products will become even more important in skincare in the future.