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Reliability and Longevity of Biological Systems: The Free-Radical Redox Timer of Aging

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Redox Signaling and Biomarkers in Ageing

Part of the book series: Healthy Ageing and Longevity ((HAL,volume 15))

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Abstract

The system approach, based on the engineering theory of reliability, integrates the concept of aging program and the free radical theory of aging into a unified pattern. The main line of assuring the high system reliability is preventive maintenance, i.e., unreliable elements should be timely replaced for novel ones ahead of the phase of their wear-out begins. This prophylaxis of failures is controlled via the longevity-assurance structures (supervisors) of the highest level of hierarchy which operate with limited (genetically preset) reliability. The stochastic malfunctions of the mitochondrial electron transport nanoreactors, which produce the anion-radicals of oxygen (O2•−, “superoxide radical”) as a by-product of oxidative phosphorylation, are of first importance. In reality, this radical is not an oxidant but a reducing agent. As the reducing agent, it affects NADH/NAD+ ratio, thereby impacting the epigenetic sirtuin regulators of metabolic repair and renewal processes. As a consequence, the oxidative-stress products and other metabolic slag accumulate with time, resulting in the impetus to autophagic or apoptotic cell death and age-associated clinical disorders. On this basis, the universal features of aging, the exponential growth of mortality rate with time (Gompertz law of mortality), and the correlation of longevity with the species-specific resting metabolism (Rubner scaling relation) are explained. Thus, from the reliability point of view, aging occurs as an inevitable consequence of the genetically preset deficiency in reliability of the biomolecular constructs, while the free radical redox timer, located presumably in cells of the hypothalamus, serves as an effective stochastic mechanism of realization of the genetical deficiency in system reliability of an organism as the whole.

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Acknowledgements

Boris V. Gnedenko, an outstanding mathematician from Kiev, was one of the Founding Fathers of the mathematical theory of reliability (Gnedenko et al. 1965). The first conference on reliability of biological systems had been held in Kiev, 1975. The first papers and books on reliability of biological systems had been published in Kiev (Grodzinsky, ed 1977, 1980; Grodzinsky et al. 1987). The reliability-theory approach as a methodology for searching the realistic mechanisms of antioxidant therapy had been first applied in collaboration with my colleagues and friends in Kiev (Gorban and Koltover 1985; Frolkis et al. 1985, 1990; Koltover et al. 1980, 1984). The first doctor dissertation on reliability and aging of biological systems had been successfully defended in Kiev at Bogomolets Institute of Physiology (Koltover 1988). Thus, located at the crossroads of Western Europe and the Orient, Kiev, had spurred the studies on reliability (“robustness”) of biological systems. It confirms the old saying of the Middle Ages that “Teaching comes from Kiev.”

This work was funded in accordance with the current scientific plans authorized and supported by the Ministry of Science and High Education of Russian Federation, projects no. AAAA-A19 119071890015-6 and AAAA-A19-119092390041-5).

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  1. Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow Region, 142432, Russia

    Vitaly K. Koltover

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  1. Department of Medical Biochemistry Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Ufuk Çakatay

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Koltover, V.K. (2022). Reliability and Longevity of Biological Systems: The Free-Radical Redox Timer of Aging. In: Çakatay, U. (eds) Redox Signaling and Biomarkers in Ageing. Healthy Ageing and Longevity, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-030-84965-8_2

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