title: Non-enzymatic molecular damage as a prototypic driver of aging.
abstract: 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.
authors.affiliation: From the Department of Biochemistry, Saint-Petersburg State University, Saint Petersburg 199034, Russia, aeeouelxglbv@gmail.com.
authors.forename: Alexey
authors.initials: A
authors.lastname: Golubev
authors.affiliation: the Horticultural Sciences Department, University of Florida, Gainesville, Florida 32611, and adha@ufl.edu.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hanson
authors.affiliation: the Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115 vgladyshev@rics.bwh.harvard.edu.
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D006801:Humans; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species
keywords: aging; damage; enzyme; enzyme mechanism; mechanism; metabolism; metabolite; metabolite damage; side reaction; side-product; spontaneous chemistry; substrate specificity