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.

The aging process: major risk factor for disease and death.

“…Many theories have been advanced to account for the aging process (18)(19)(20). For example, the effects of aging have been attributed to molecular crosslinking (21), changes in immunological function (22), damage by free radical reactions (23) and senescence genes in the DNA (24). No one theory is generally accepted: "this remarkable process remains a mystery" (25); "it is doubtful that a single theory will explain all the mechanisms of aging" (26,27).…”

Excess Dietary Aluminum Increases <i>Drosophila’s</i>Rate of Aging

“…Thus the accumulation of aluminum with aging may be a general phenomenon. Bjorksten [1980] has proposed that the crosslinking properties of aluminum may make it an important factor in the development of senescence. DeBoni et al [ 1974] and Karlik et al [1980] have shown that aluminum binds to chromatin and forms complexes with DNA.…”

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

“…Some of these implicate quite specific sources of damage, for example macromolecular crosslinkage (Bjorksten 1968), accumulation of toxic metabolic wastes (Sheldrake 1974), racemisation of amino acids (DeLong and Poplin 1977), macromolecular damage caused by free radicals (Harman 1956), or the accumulation of defects in cell membranes (Zs-Nagy 1978; Cremer et al 1981). Others are more general, such as the somatic mutation theory (Szilard 1959;Curtis 1966;Burnet 1974) or the protein error theory (Medvedev 1962;Orgel 1963Orgel , 1973.…”