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The cross-linking/glycation hypothesis of aging
 The cross-linking hypothesis is based on the observation that with age, our proteins, DNA, and other structural molecules develop inappropriate attachments or cross-links to one another. These unnecessary links or bonds decrease the mobility or elasticity of proteins and other molecules. Proteins that are damaged or no longer needed are normally broken down by enzymes called proteases, and the presence of cross-linkages inhibits the activity of proteases. These damaged and unneeded proteins, therefore, stick around and can cause problems.
One of the main ways cross-linking occurs is through a process called glycosylation or glycation. Glucose molecules can stick to proteins, then transform into a brownish molecule called an advanced glycosylation endproduct, or AGE. When both of the sticky ends of AGEs adhere to neighboring proteins, they form permanent, disabling cross-links.
Some research supports the hypothesis that cross-linking contributes to aging. Cross-linking of the skin protein collagen has been shown to be at least partly responsible for wrinkling and other age-related changes in skin. Cross-linking of proteins in the lens of the eye is also believed to play a role in age-related cataract formation. Researchers speculate that cross-linking of proteins in the walls of arteries or the filtering systems of the kidney account for at least some of the atherosclerosis (hardening of the arteries) and age-related decline in kidney function observed in older adults. Another study conducted at the Bjorksten Institute in Wisconsin treated brain tissue from young animals with known cross-link-inducing compounds. That brain tissue soon looked quite similar to older brain tissue with its naturally cross-linked brain proteins, adding evidence in support of this theory of aging.
Recently, scientists have found evidence that glycation contributes to the formation of beta-amyloid, the protein that clumps together in the brains of Alzheimer’s patients.
Somewhat indirect experimental evidence in support of the cross-linking theory of aging can be found in studies that look at drugs that prevent cross-linking, and the impact of taking those drugs on the various components of the aging process. Studies done in China and in the United Kingdom on the molecule carnosine are provocative. Carnosine occurs in very low concentrations in the brain and other tissues. In the laboratory, carnosine has been shown to delay the senescence or aging of human cells called fibroblasts. Carnosine works by preventing cross-linking of proteins. The more recent Chinese studies suggest carnosine might be of benefit in delaying the formation of cataracts, in which cross-linking is thought to play a part.
Although many scientists agree that cross-linking of proteins, and perhaps the cross-linking of DNA molecules as well, is a component of aging, it is likely only one of several mechanisms that contributes to aging.
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