Macromolecules damaged by covalent modifications produced by chemically reactive metabolites accumulate in the slowly renewable components of living bodies and compromise their functions. Among such metabolites, catecholamines (CA) are unique, compared with the ubiquitous oxygen, ROS, glucose and methylglyoxal, in that their high chemical reactivity is confined to a limited set of cell types, including the dopaminergic and noradrenergic neurons and their direct targets, which suffer from CA propensities for autoxidation yielding toxic quinones, and for Pictet-Spengler reactions with carbonyl-containing compounds, which yield mitochondrial toxins. The functions progressively compromised because of that include motor performance, cognition, reward-driven behaviors, emotional tuning, and the neuroendocrine control of reproduction. The phenotypic manifestations of the resulting disorders culminate in such conditions as Parkinson’s and Alzheimer’s diseases, hypertension, sarcopenia, and menopause. The reasons to suspect that CA play some special role in aging accumulated since early 1970-ies. Published reviews address the role of CA hazardousness in the development of specific aging-associated diseases. The present integrative review explores how the bizarre discrepancy between CA hazardousness and biological importance could have emerged in evolution, how much does the chemical reactivity of CA contribute to the senescent phenotype in mammals, and what can be done with it.
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