How does the cross-linking theory explain changes in aging tissues?

The cross-linking theory of aging posits that as organisms age, chemical bonds—or cross-links—form within and between molecules of collagen, a vital fibrous protein.12

In youth, collagen exists in a more soluble, flexible form. Over time, however, the accumulation of these cross-linkages leads to increased crystallinity and rigidity in tissues such as skin, tendons, and blood vessels, which manifests as a general loss of elasticity and body stiffness.12

Beyond structural proteins, the theory suggests that similar cross-links may form in other essential molecules, such as enzymes. By altering the structure and shape of these molecules, cross-linking can impair their ability to function within the cell. Furthermore, these changes decrease the permeability of tissues, hindering the transport of necessary nutrients, hormones, and antibodies. This process is chemically analogous to the tanning of hide into leather, leading researchers to investigate whether substances that inhibit cross-linking could potentially retard aspects of the aging process.123