Similarly to technical devices, biological constructions are not perfectly reliable in operation, i.e. malfunctions happen alternating with normal operation functions. In engineering, reliability is defined as the ability of a device to perform its function for a given time under given specific conditions. The same definition of reliability fits biological systems. The conferences, which were initiated by Dmytro Grodzinsky, Ukrainian Academy of Sciences in Kiev, Ukraine, starting from 1975, have given a strong impetus to research in this direction (Grodzinsky, 1977). The reliability approach to the free-radical theory of aging is based on the simple general principles that (i) biomolecular constructions are designed in keeping with the genetic program in order to perform the programmed preset functions; (ii) all of them operate with limited reliability; (iii) timely replacement or prophylaxis of unreliable functional elements, i.e. metabolic turnover, is the main line of assuring high systems reliability; (iv) there is a finite number of critical elements which perform the supervisory functions over the preventive maintenance; (v) the supervisors operate with the limited reliability. On this basis, universal features of aging, such as the exponential growth of mortality rate with time and correlation of longevity with the species-specific resting metabolism, are naturally explained. The stochastic malfunctions of mitochondrial electron transport nanoreactors, which produce oxygen radical anions O2●– as the by-products of respiration, seem to be of first importance. As the reducing agent, O2●– affects the ratio of NADH/NAD+ and, by changing the activity of sirtuins, slows down renewal of biomolecular constructs. Furthermore, the mitochondrial O2●– production tends to increase with aging (Nohl, Koltover, Stolze, 1993; Payne, Chinnery, 2015). As a consequence, the oxidative-stress products and other metabolic “garbage” accumulate with the resulting impetus to autophagic or apoptotic cell death and the age-associated clinical disorders. Basing on this reliability-theory approach, one can estimate that the longevity of human brain could reach 250 years should the antioxidant defense against the free-radical failures be perfect. Hence, the free-radical redox timer serves as the effective stochastic mechanism of realization of the programmed deficiency in reliability of biomolecular constructs. The rate constants and concentrations of the so-called antioxidants are small to compete with the antioxidant enzymes for reactive oxygen species (ROS). However, the antioxidants provide the preventive protection against ROS, i.e. prophylactic maintenance via the organism’s neuro-hormonal system and/or microbiota (Koltover, 2009; 2016). Thus, the systems reliability approach serves as heuristic methodology in searching realistic mechanisms of antioxidant therapy of aging.
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