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Non-enzymatic molecular damage as a prototypic driver of aging

Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 292, Issue: 15, Page: 6029-6038
2017
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A Tour of Some of the Molecular Damage Involved in Aging

The intricate molecular machinery found in cells only functions correctly when it is undamaged, meaning formed of the right atoms and bonds, and that often sizable structure correctly arranged into a particular three-dimensional shape. A cell is essentially a liquid bag of molecules that are constantly coming into contact with one another, however. Large numbers of these molecules react in inappro

Review Description

The chemical potentialities of metabolites far exceed metabolic requirements. The required potentialities are realized mostly through enzymatic catalysis. The rest are realized spontaneously through organic reactions that (i) occur wherever appropriate reactants come together, (ii) are so typical that many have proper names ( e.g. Michael addition, Amadori rearrangement, and Pictet-Spengler reaction), and (iii) often have damaging consequences. There are many more causes of non-enzymatic damage to metabolites than reactive oxygen species and free radical processes (the “usual suspects”). Endogenous damage accumulation in non-renewable macromolecules and spontaneously polymerized material is sufficient to account for aging and differentiates aging from wear-and-tear of inanimate objects by deriving it from metabolism, the essential attribute of life.

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