Free-radical redox timer, sirtuins and aging: from chemistry of free radicals to systems theory of reliability

Abstract

Abstract The goal of this chapter is to demonstrate how the systems theory of reliability (“robustness”) unites the aging program and the aging stochastics. On this basis, the universal features of aging, exponential growth of mortality rate with time, and correlation of longevity with species-specific resting metabolism are naturally explained. The stochastic malfunctions of the mitochondrial electron transport nanoreactors, which produce oxygen anion-radicals (O2•–) as by-products of oxidative phosphorylation, are of first importance. As the reducing agent, O2•– affects NAD(P)H/NAD(P)+ ratio, thereby impacting the epigenetic sirtuin regulators of metabolic repair and renewal processes. As a consequence, oxidative-stress products and other metabolic slag accumulate with resulting an impetus to autophagic or apoptotic cell death and age-associated clinical disorders. Thus the free-radical redox timer, located presumably in the hypothalamus, serves as the effective stochastic mechanism of the realization of genetically preset deficiency in the system’s reliability while sirtuins serve as the promotion agents of free radical violations.