Free radical mechanisms of aging processes under physiological conditions.

Free radical theory of aging predicts crucial role for free radicals produced by external factors (environmental contamination, irradiation, etc.) or pathological disorders (hereditary diseases or infections) in the initiation of aging. Does it mean that under hypothetical completely physiological conditions aging processes could be fully suppressed? To answer this question, we will consider the possible mechanisms of free radical formation in such hypothetical state. There are two major mechanisms, which are responsible for free radical-mediated damage in a living organism: superoxide overproduction by mitochondria and nonenzymatic lipid peroxidation. Superoxide overproduction causes the inhibition of nitric oxide formation and bioavailability, one of principal characteristics of aging, while nonenzymatic lipid peroxidation, which is already demonstrated at physiological conditions, produces toxic isoprostanes. We suggest that major initiators of free radical-mediated damaging processes leading to aging at physiological state are oxidizable components of diet. The possibility of inhibition of aging processes by supplementation of nontoxic antioxidants and calorie restriction is discussed. Scheme demonstrating the potential mechanisms of starting the free radical-mediated aging processes is presented, which are discussed on the grounds of known literature data.