H+ Magazine
Covering technological, scientific, and cultural trends that are changing–and will change–human beings in fundamental ways.

Editor's Blog

John Colman
June 10, 2009


Oxygen MoleculeAs humans, we are caught in a cruel bind. The oxygen that sustains us is also responsible for the aging process itself and the degenerative diseases that are part of aging. We are not alone in this regard—all other mammals and aerobic organisms are utilizing oxygen as a source of energy and suffer the same consequences. We survive in a narrow band of safety, protected only by the enzymes that air-breathing organisms have developed during their evolution from plant life to animal life.

Oxygen by itself is not particularly toxic at normal pressures, but when experimental animals are placed in pure oxygen at five to ten times the normal sea-level pressure, they die in minutes or hours. By itself, oxygen (especially at the normal 20% levels found in ordinary air) is not responsible for the rusting that occurs to iron. The iron acts as a catalyst, and along with water produces more reactive, partially reduced forms of oxygen that actually cause the rusting process.

Partially reduced forms of oxygen are themselves free radicals and extremely toxic. Thankfully, we reduce 80% of our oxygen directly to water through the action of the enzyme cytochrome oxidase. This four-stage reduction of oxygen to water produces no detectable free radicals. The energy generated from this enzyme reduces oxygen directly to water and, in turn, the cells utilize the released energy and deposit it in the energy storage molecule ATP (adenosine triphosphate) which is present in all cells.

The real problem is that the other 20% step-by-step reduction of oxygen by other enzymes produces most of the free radicals in the body. A one-step addition of an electron to oxygen produces a superoxide radical, a two-step reduction of oxygen produces hydrogen peroxide, and a three-step reduction of oxygen produces the most powerful of them all, the hydroxyl radical. The final, four-step reduction produces water. All of these intermediate, partially reduced forms of oxygen are free radical rogue molecules, which react with and severely damage our DNA, our key enzymes and any other proteins they contact. This is the fundamental cause of the aging process.

Trees and plants breathe in carbon dioxide and release oxygen as a toxic by-product of their respiration. Trees have been reported to live up to 4,000 years. By comparison, land tortoises, the longest living air breathing animals are estimated to live up to 300 years. Tortoises, alligators, fish and amphibians are all poikilotherms, animals whose body temperatures are determined by their surroundings. As mammals, humans and other homeotherms have a constant body temperature that they maintain from conception to death.

Damaged DNAThe burden of maintaining a constant body temperature produces an abundance of free radicals which would strongly tend to shorten lifespan, according to the “metabolic” and “rate of living” theories proposed over the past 80 years. However, later gerontology research has disproven or discredited metabolic rate theories, and observations of animals with lower body temperatures show that they do not necessarily live longer than animals with higher body temperatures. How can this contradiction be explained?

In a landmark 1984 study, Richard Cutler at the Gerontology Research Center of the National Institute of Health compared numerous antioxidant levels in mammals from mice to humans, their metabolic rates and their maximum species lifespans. The antioxidant levels of tissue and serum levels of the enzyme S.O.D. (superoxide dismutase) correlated most strongly with lifespan, humans having the highest S.O.D. levels of all the mammals. Our closest relative, the chimpanzee, has about half the S.O.D levels (40 micrograms per ml.) of humans (90 micrograms per ml.) and about half the lifespan. Cutler then multiplied the maximum longevity for each species in years by their specific metabolic rate to determine the L.E.P. (lifespan energy potential) or total calorie output over the entire lifespan for each species. It was clear, then, that humans have the highest L.E.P. of all the mammals and although we have a very high metabolic rate we live a very long, disease-free lifespan. The metabolic rate of living theories were disproven, and equally important factors were discovered to be at play in determining lifespan. Internally-produced antioxidant enzyme levels have the major role in determining longevity.



Voluminous studies conducted over the last 40 years prove that the by-products of oxygen utilization are the main contributors of aging and disease, i.e. superoxide radicals, hydrogen peroxide and hydroxyl radicals. This research also shows that the body’s own production of internally produced enzymes –- superoxide dismutase (S.O.D.), catalase and glutathione peroxidase, reduce oxygen to water with little free radical production. These endogenous (internally produced) enzymes are vastly more potent than dietary antioxidants, such as vitamin C. S.O.D., for example, is 3,500 times more potent than vitamin C at reducing superoxide radical. Antioxidant levels of S.O.D., catalase and the like are programmed to decline with age and this correlates with a rise in all the degenerative diseases in humans, including cancers, diabetes, Alzheimer’s and Parkinson’s disease, multiple sclerosis and fibromyalgia.

People will not restrict their dietary intake severely or eat on alternate days. Drugs or supplements are the only alternative.

Genetically inherited differences in S.O.D. levels can vary as much as 50% in humans, which helps to explain why some people are prone to degenerative diseases early in life as opposed to others who lead disease-free lives. In humans and other mammals antioxidant enzyme levels normally decline with age and levels of inflammatory gene expression, like COX-2 and IL6, increase with age. The only exception to these changes has been found in calorie restriction experiments with mice, primates and humans. Calorie restriction experiments were first conducted in 1932, and it was discovered that the longevity of mice increased 50%. Later experiments showed that animals fed normally one day and deprived of food the next day also lived 50% longer. Human experiments with calorie restriction at 50% daily intake or eating on alternate days also maintained youthful antioxidant enzyme levels and youthful expression of inflammatory genes.

It is generally accepted that people will not restrict their dietary intake severely or eat on alternate days. Therefore drugs or supplements that create the effects of keeping S.O.D. and other antioxidant levels at youthful or higher levels are the only alternative to these inevitable “programmed” aspects of the aging process. The two scientists who discovered and jointly published the true function of S.O.D. in 1969, Irwin Fridovich and Joseph McCord, have proceeded in two different directions to solve the problem of raising levels of S.O.D.

Irwin Fridovich has spent over 30 years developing S.O.D. mimetics that duplicate the powerful antioxidant effects of real S.O.D. He has discovered some very potent S.O.D. mimetics based on the natural porphyrin molecule, which is similar to chlorophyll. Unfortunately, these modified porphyrins are considered experimental compounds and are not yet approved for human use.

Aging Hands and LeavesJoe McCord, however, has pursued a different approach, going through the database of plant extracts that stimulate the body to produce endogenous S.O.D. He is selling a mixture of S.O.D. stimulating herbs under the trade name of Protandim, which has been shown in a published human clinical trial to raise S.O.D. levels.

The race to produce S.O.D. mimetics or endogenous stimulants of S.O.D. is ongoing. The most promising natural compound has been found in broccoli extracts: D3T (1,2-dithiole, 3-thione). It not only raises S.O.D. and all the other endogenous antioxidants (catalase, glutathione peroxidase and glutathione), it also raises the enzyme glutathione transferase, which neutralizes the toxic metabolites formed by the liver.

When this compound is available or found in higher concentrations in broccoli or other natural cruciferous vegetables, it will solve two huge anti-aging problems¬—the problem of S.O.D. production within the human body and the production of stage II liver enzymes, which will reduce cancers by neutralizing the carcinogens formed during stage I liver detoxification.

7 Comments

    All of this free-radicals research leaves me wondering: If something (e.g. free radicals) damages our DNA over time, then how come our species is still alive?
    As reproduction also proceeds via DNA, errors should accumulate over generations, apparently though, they don't.

    What about taking SOD in capsules or pills?

    The Fight Aging weblog has published a critique of this article.

    Superoxide dismutase is a protein enzyme. Your stomach and intestines contain acids and enzymes (trypsin and pepsin) whose purpose it is to break down proteins into their constituent enzymes. As a result, in order for protein drugs to be effective, they need to be injected. This is why there's no magical insulin pill for diabetics; insulin is a protein, so taking it orally would do nothing.

    Injecting SOD probably wouldn't work either, since you need SOD inside each cell, and it's very unlikely that a mechanism exists in most cells for transporting SOD across the cell membrane.

    I've also heard that sugar causes aging as well. But Telomerase is the ultimate arbiter of cell longevity. Our cells age because their telomeres shorten after mitosis. The only exceptions I believe are: germline (for Jens-Wolfhard Schicke), perhaps adult stem cells, and cancer cells. I don't doubt that free radicals of oxygen can cause damage but I think the aging that we experience is a matter of our cellular clock, not oxygen. Perhaps it is wishful thinking that we can stop our aging by eating differently.

    After reading this article, I had the creeping suspicion that it was a well-written disguised advertisement for Protandim. Which may or may not be a good product, but it's definitely got some slick words pushing it.

    The link two comments below this to the Fight Aging critique goes into some good specifics about why not to trust it.

    Hi Jens - good question. In fact that's thought to be one of the reasons for recombination - it helps purge damaged DNA. Also, the germ line (the lineage of sperm & eggs) is isolated & much more protected than the cells in the rest of your body, so it doesn't get damaged as much.

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