What is the rate-limiting step towards aging? Chemical reaction kinetics might reconcile contradictory observations in experimental aging research.

GeroScience
Sascha Kunath, Bernd Moosmann

Abstract

Modern geroscience is divided as regards the validity of the free radical theory of aging. Thermodynamic arguments and observations from comparative zoology support it, whereas results from experimental manipulations in representative animal species sometimes strongly contradict it. From a comparison of the multi-step aging process with a linear metabolic pathway (glycolysis), we here argue that the identification of the rate-limiting kinetic steps of the aging cascade is essential to understand the overall flux through the cascade, i.e., the rate of aging. Examining free radical reactions as a case in point, these reactions usually occur as chain reactions with three kinetically independent steps: initiation, propagation, and termination, each of which can be rate-limiting. Revisiting the major arguments in favor and against a role of free radicals in aging, we find that the majority of arguments in favor point to radical propagation as relevant and rate-limiting, whereas almost all arguments in disfavor are based on experimental manipulations of radical initiation or radical termination which turned out to be ineffective. We conclude that the overall lack of efficacy of antioxidant supplementation (which fosters termination) ...Continue Reading

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Citations

Sep 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mariona JovéReinald Pamplona
Aug 31, 2020·Redox Biology·Sascha KunathBernd Moosmann
Mar 14, 2021·Aging·Bernd Moosmann

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