THE CROSSLINKAGE THEORY OF AGING

Abstract: For many decades the theory and practice of cross‐linking (bonding that ties two or more large molecules together side to side) have been developed in industry, but only since the 1940's has the theory been considered in the field of medicine as a primary reaction underlying age‐dependent changes. Crosslinking is damaging to the tissues and involves loss of elasticity, reduced swelling capacity, increased resistance to hydrolases and probably enzymes generally, and thus an increase in molecular weight and a tendency toward embrittlement. There is a growing amount of direct evidence and much indirect evidence for postulating the relationship between crosslinking and aging. Crosslinking agents present in the living organism include aldehydes, lipid oxidation products, sulfur, alkylating agents, quinones, free radicals induced by ionizing radiation, antibodies, polybasic acids, polyhalo derivatives and polyvalent metals. The latter four types of compound are slow‐acting but can also accumulate in the body to form a frozen metabolic pool. Sufficient amounts of all these potential crosslinking materials are present in the body to make the changes of aging unavoidable.