In 1942 Johan Bjorksten hypothesized that cross-linking played an important part in the aging process.
This cross-linking took place in proteins such as the collagen protein, which is found in skin, tendons, and ligaments.

The collagen protein resembles the legs of a ladder that has very few rungs between them. In addition, each ladder is bound to those beside it by other rungs - the cross-links. As we age, the immune system is less able to clean the blood of impurities, including excess amounts of glucose molecules.

These glucose molecules combine with protein to form advanced glycation end products, causing yellowing of the teeth for example, and are able to form further cross-links between the ladders of the collagen proteins. In addition, this process gives rise to free radicals as well.

As the cross-links in collagen proteins become more numerous, they hold adjoining ladder rungs more tightly. This causes the collagenous tissue to shrink, which in turn causes skin to shrink, and become less pliable. Further, these cross-links may impede the movement of nutrient and waste between cells.