Why Do We Age? | Crosslinking and Advanced Glycation End Products (AGEs)


  • Crosslinks are connections or links between proteins that make up our tissues.
  • Linking proteins together makes the tissues more stiff and rigid.
  • This rigidity hardens blood vessels, lung tissue and cartilage, contributing to various aging-related diseases, like hypertension, pulmonary problems and osteoarthritis.
  • During aging, more and more crosslinks form in our tissues. Many of these crosslinks are made of sugar.
  • Consuming a diet with little sugars can slow down the formation of crosslinks.

Crosslinks are formed everywhere in our body. They glue together the proteins that make up our tissues, contributing to aging and aging-related diseases.

What are crosslinks or Advanced Glycation End products (AGEs)?

The formation of crosslinks is one of the reasons why we age. 

But — what are crosslinks, how are they formed, and how do they contribute to aging?

When we get older, crosslinks are created between the proteins that make up our tissues.

Crosslinks glue proteins together, making our tissues less flexible and more rigid.

Many of these crosslinks are formed by sugar. When a sugar molecule nestles between two protein strands, it creates a connection, or crosslink, between these proteins. 

When proteins are linked in this way, the tissue made up of these proteins becomes stiffer. 

These sugar-crosslinks are also called “Advanced Glycation End products” (AGEs).

Sugar-based crosslinks (red) are formed between collagen proteins (black strands). A young person has few crosslinks, an elderly person has many crosslinks.

The role of crosslinks in aging and aging-related diseases

Crosslinked collagen and elastin proteins in the skin makes the skin less flexible, which contributes to wrinkles. 

The crosslinking of collagen and elastin proteins in the blood vessels makes the blood vessels harder and less flexible, contributing to hypertension.  

Crosslinked proteins in the eye lens play a role in cataract, an aging-related eye disease in which the eye lens becomes more opaque.

Crosslinked proteins in the kidney hinder the proper filtration of the kidney, which contributes to the aging-related decline of kidney function. 

Crosslinking in the lungs makes the lung tissue stiffer, which increases the risk of pneumonia and other lung infections.

Crosslinked cartilage makes it less flexible and contributes to osteoarthritis. Note: we discuss various ways to reduce osteoarthritis here.

You can see crosslinking happening even in your own kitchen. The brownish, hard crust that forms when you heat your chicken is caused by crosslinking. 

When you toast bread, it also becomes hard and brown due to crosslinking. 

And, in nature, the bark of trees can be very hard due to crosslinking. 

Not all crosslinks are the same

There are different kinds of crosslinks in our body. Examples of such crosslinks are glucosepane and pentosidine crosslinks.

Glucosepane crosslinks are complex, tough-to-break crosslinks. Scientists are looking at ways to break these crosslinks in order to make tissues more flexible and younger again.

Sugar, starches and crosslinking

As mentioned above, sugar molecules primarily cause these crosslinks. 

This also explains why people with type 2 diabetes, who often have high blood sugar levels, also have much more crosslinking. 

This crosslinking or “glycation” of their tissues is one reason why people with diabetes have much more risk of hypertension, heart disease, eye problems (e.g. cataract) and kidney dysfunction.

This is why some scientists call type 2 diabetes an “accelerated aging disease” or view diabetes as a premature aging disease. 

Sometimes, one can even see the crosslinking with the naked eye in diabetes patients. These patients have very fine wrinkles, especially on the cheeks, and a yellowish hue of their skin, which is sometimes even more pronounced on the palms of their hands. These kinds of wrinkles and color changes are caused by extensive crosslinking in the skin. 

How unhealthy food contributes to crosslinking

Many foods are very sugary and when consumed cause high sugar peaks in the blood, which contribute to crosslinking. 

This is especially the case for foods with a high glycemic index and glycemic load, which are a measure for the height of the sugar peak in your blood caused every time when you consume a food.

Not only do sugary foods like candy, cake, cookies, and soda cause high sugar peaks, starchy foods like bread (especially white bread), rice, pasta and potatoes can also make blood sugar levels spike, contributing to crosslinking and activating all other kinds of pro-aging pathways, like insulin and IGF receptors.

Therefore, it’s important to consume a low glycemic index or glycemic load diet, which is a diet that consists of foods that don’t typically cause high sugar peaks. These are foods like vegetables, legumes, mushrooms, fish, white meat (like chicken), and so on. 

Combining these healthy foods with vinegar and fats (which delay gastric emptying), further reduces the sugar peaks after every meal. 

We explain more about the best diet for longevity here

Crosslinking can be considered as one of the many reasons why we age. Other causes or “hallmarks of aging” are discussed here

NOVOS’ approach to crosslinking

NOVOS Core contains natural ingredients that can help the body to manage crosslinking, including theanine, glucosamine, and glycine.

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