[Frontiers in Bioscience 14, 3899-3912, January 1, 2009]

Superoxide and nitric oxide in senescence and aging

Igor Afanas'ev

Vitamin Research Institute, Moscow, Russia

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Superoxide in aging and senescence
3.1. Enhanced production of superoxide by mitochondria in aging cells
3.2. Enhanced production of superoxide by NADPH oxidase and xanthine oxidase with aging
3.3. A decrease in superoxide dismutase activity with age
3.4. A decrease in superoxide dismutase activities with the age in humans
3.5. Controversy in the effects of aging on superoxide dismutase activity
4. Interplay between superoxide and nitric oxide in aging and senescence
5. Cyclooxygenase-catalyzed free radical overproduction in the age
6. Gene regulation of free radicals in the age
7. Free radical-mediated damage in the age through signaling by protein kinases
8. Free radical-mediated apoptosis in the age
9. Mechanisms of free radical-mediated damage in aging and senescence
9.1. Mitochondria as the origin of aging development
9.2. Superoxide-mediated enzymatic catalysis
10. What could be the primary causes of aging and senescence development?
11. Antioxidant treatment against aging and senescence; possibility of enlargement of life span
11.1. Calorie restriction
11.2. Antioxidants
12. Conclusions
13. References

1. ABSTRACT

In this review some aspects of free radical theory of aging are discussed. Many new and interesting findings concerning the role of physiological free radicals superoxide and nitric oxide in senescence and aging development are considered and the mechanisms of processes mediated by these radicals are discussed. It has been known for a long time that being themselves mostly harmless species, superoxide and NO are precursors of really reactive species hydroxyl radicals and peroxynitrite, the initiators of aging and various pathologies. However, contemporary studies demonstrate the other maybe more important ways of damaging activity of physiological free radicals. Numerous studies show that lessening of NO production and its bioavailability could be a starting point of aging development. It results in a decrease in NO inhibition of mitochondrial cytochrome c oxidase and an increase in dioxygen consumption. That in its turn leads to an increase in the production of superoxide and the other reactive oxygen and nitrogen species and initiation of apoptosis, In conclusion the possibilities of pharmacological intervention with antioxidants and other antiradical procedures to suppress aging and senescence or even to expand the life span of animals are considered.