Calorie Restriction with Optimum Nutrition
Home • Forum • What's New • What to Eat • Short/Long-Term Benefits of CR • Books • Links, References & Resources
Supplements • 2000 Poll: Graphics • Poll: Statistics • Theories of Aging • CR Mimetics • Science and Research • CRONies

Oxygen Toxicity and Free Radical

Oxygen toxicity is a toxic effect in many -- but not all -- living organisms caused by a species of oxygen. Oxygen has two aspects, one benign and the other malignant. Those organisms that avail themselves of the enormous metabolic advantages provided by dioxygen (O2) must defend themselves against its toxicity. The complete reduction of one molecule of O2 to two of water (H2O) requires four electrons; therefore, intermediates must be encountered during the reduction of O2 by the univalent pathway. The intermediates of O2 reduction, in the order of their production, are the superoxide radical (O2-), hydrogen peroxide (H2O2), and the hydroxyl radical (HO•).

The intermediates of oxygen reduction, rather than O2, itself, are probably the primary cause of oxygen toxicity. It follows that defensive measures must deal with these intermediates. The superoxide radical is eliminated by enzymes that catalyze the following reaction:

O2 + O2 + 2H+ ⇌ H2O2 + O2

These enzymes, known as superoxide dismutases, have been isolated from a wide variety of living things.

Hydrogen peroxide (H2O2) must also be eliminated, and this is achieved by two enzymatic mechanisms. The first of these is the dismutation of H2O2 into water and oxygen, a process catalyzed by catalases. The second is the reduction of H2O2 into two molecules of water at the expense of a variety of reductants, a process catalyzed The multiplicity of superoxide dismutases, catalases, and peroxidases, and the great catalytic efficiency of these enzymes, provides a formidable defense against O2- and H2O2. If these first two intermediates of O2 reduction are eliminated, the third (HO•) will not be produced. No defense is perfect, however, and some HO• is produced; therefore its deleterious effects must be minimized. This is achieved to a large extent by antioxidants, which prevent free-radical chain reactions from propagating.

The apparent comfort in which aerobic organisms live in the presence of an atmosphere that is 20% O2 is due to a complex and effective system of defenses against this peculiar gas. Indeed, these defenses are easily overwhelmed, and overt symptoms of oxygen toxicity become apparent when organisms are exposed to 100% O2. For example, a rat maintained in 100% O2 will die in 2 to 3 days.

A free radical is any molecule or atom which possesses one unpaired electron. There are some molecules which contain more than one unpaired electron (for example, oxygen); they normally are not considered as free radicals. Free radicals can be chemically very reactive (for example, the methyl radical) or they can be very stable entities (e.g., nitric oxide).

Free radicals can be grouped into three major classes: atoms (for example, H, F, and Cl), inorganic radicals (for example, OH, CN, NO2, and ClO3), and organic radicals (for example, CH3, CH3CH2, and C6H6-). Such radicals are of great importance since they often appear as intermediates in thermal and photochemical reactions. Radicals are also known to initiate and propagate polymerization and combustion reactions.

In general, free radicals are formed by the rupture of a bond in a stable molecule with the production of two fragments, each with an unpaired electron. The resulting free radicals may participate in further reactions or may combine to reform the original compound.

There are many ways in which radicals can be generated among these are thermal decomposition, electric discharge photochemical reactions, electrolysis at an electrode such as mercury or platinum, rapid mixing of two reactants, and gamma- or x-ray irradiation.

Further reading:

The free radical theory of aging (Nathan C. Nelson, Ohio State Univ.)

The Free Radical Theory of Aging Matures (KENNETH B. BECKMAN AND BRUCE N. AMES; PHYSIOLOGICAL REVIEWS Vol. 78 No. 2 April 1998, pp. 547-581)

The Aging Process (Denham Harman; PNAS | November 1, 1981 | vol. 78 | no. 11 | 7124-7128)

Mitochondrial Free Radical Production and Aging in Mammals and Birds (GUSTAVO BARJA; Annals of the New York Academy of Sciences Volume 854 Page 224 - November 1998)

A network theory of ageing: the interactions of defective mitochondria, aberrant proteins, free radicals and scavengers in the ageing process (Kowald A, Kirkwood TB.; Mutat Res. 1996 May;316(5-6):209-36)

Mitochondrial free radical generation, oxidative stress, and aging (Cadenas E, Davies KJ.; Free Radic Biol Med. 2000 Aug;29(3-4):222-30)

Mitochondrial theory of aging matures -- Roles of mtDNA mutation and oxidative stress in human aging (Wei YH, Ma YS, Lee HC, Lee CF, Lu CY; Department of Biochemistry, National Yang-Ming University, Taipei, Taiwan, R.O.C.)

Dying before Their Time -- Studies of prematurely old mice hint that DNA mutations underlie aging

Reduced free-radical production and extreme longevity in the little brown bat (Myotis lucifugus) versus two non-flying mammals (Mech Ageing Dev. 2004 Jan;125(1):11-20; Brunet-Rossinni AK)

Emerging Area of Aging Research: Long-lived Animals with "Negligible Senescence"

Comparative Longevity in Negligibly Senescent Species (Power Point presentation)

Damage-Based Theories of Aging

Google Scholar search for "free radical mitochondrial theory"

Top of page