Dietary restriction downregulates free radical and lipid peroxide production: plausible mechanism for elongation of life span.

Dietary restriction elongates life span by suppressing age-related diseases in experimental animals. It has received a great deal of attention in connection with the relationship between aging, nutrition, and oxidative stress because oxidative injury in several tissues is a prominent feature in the aging process. Although the oxidative stress theory of aging has currently gained popularity, the premise from which this hypothesis was derived is paradoxical because the same oxygen, that supports life in one hand threatens survival and promotes aging in the other. Until recently, no single experimental paradigm could offer satisfactory mechanistic explanations for this complex issue. Recent investigations using the life-extending dietary restriction regimen could offer satisfactory mechanistic explanations for this apparent self-contradiction to life. The modulation of free radical-induced oxidative stress provided sufficient data to support the notion that dietary restriction's antiaging effect may come from its ability to tightly regulate the oxidative status of an organism. The result is the maintenance of cellular homeostasis, a hallmark of dietary restriction's action in the extension of life span. To date, we reported that dietary restriction (maintained on 60% of ad libitum feeding) suppresses age-related oxidative damage by modulating the amount as well as the fatty acid composition of tissue phospholipids. These remarkable findings have been incorporated into the new "membrane peorxidation cycle" concept. The intervention of this cycle appears to be an evolutionary process that the dietary restricted rats have adapted as a strategy to protect the membrane in an oxidative environment.