Why and How Do We Age? A Single Answer to Two Questions


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Abstract

The chemical properties of the compounds involved in metabolic processes, even the core ones, such as glycolysis and the Krebs cycle, are not confined to the properties utilized in enzymatic reactions; they include the ability to spontaneously form covalent bonds with other compounds, including macromolecule components. The effects of the gene that codes for an enzyme catalyzing the formation of a metabolite with such properties may be regarded as antagonistically pleiotropic. The effects implemented via the product of the reaction catalyzed by the enzyme coded for by the gene are required to maintain viability. As for the effects mediated by the spontaneous formation of covalent bonds between this product and slowly renewable macromolecules, they are increasingly deleterious with time, which is provided by the positive effects. Thus, the antagonistically pleiotropic effects are not late-acting, as it is commonly believed, but are cumulative. Since these effects are inseparable from the metabolism, they may be labeled “parametabolic.” The driving force produced by these effects is sufficient for aging to take place in any system that exists due to metabolic processes therein, whereas its genetic information is stored and some other functions, e.g. bearing, are performed by macromolecular components, which feature a much slower turnover than that of the metabolites. Thus, we age because of the chemical properties of our constituents, and we do so as determined by these properties implemented under the conditions in our bodies. Aging is neither a direct product of evolution via natural selection (such as a program determining lifespan) nor a byproduct (delayed payment for current advantages). Aging results from the limitations imposed by the immanent physicochemical properties of metabolites on the capabilities and outcomes of the evolution by natural selection; this is what distinguishes aging from the tear and wear of inanimate objects.

About the authors

A. G. Golubev

Petrov National Medical Research Center of Oncology

Author for correspondence.
Email: lxglbv@rambler.ru
Russian Federation, St. Petersburg, 197758


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