For more than a half century, one of the enduring explanations of aging has been the Free Radical Theory of Aging. The concept is that toxic oxidants in biological systems attack cellular components, damage organs, cause age-related diseases such as cancer and arteriosclerosis, and eventually lead to death. A long-standing question has been whether enhanced presence of antioxidants could increase longevity. Scientists recently tested this hypothesis in animals. Their study is the first to show in mammals the importance of antioxidants in prolonging life. For details from an article published in the peer-reviewed journal Science, click here. "Extension of murine life span by over expression of catalase targeted to mitochondria." Science. 2005 Jun 24;308(5730):1875-6. This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

By Benjamin V. Treadwell, Ph.D.

A group of investigators recently reported the results of a study demonstrating a 20% increase in life span in animals genetically engineered to produce an excess of the enzyme, catalase. Is there really one enzyme that can enable you to live longer? If so, how does it work? Can you pop it as a pill?

The Enzyme Catalase

To answer these questions, let’s take a look at where the enzyme catalase comes from and how it operates. Our state of health – and indeed our longevity – depend on the vitality of the cells comprising the tissues and organs of the body. The cells, in turn, consist of numerous sub-cellular structures, organelles, which include the mitochondria. These minute cellular compartments are responsible for virtually all the energy the cell requires to keep the organs of the body healthy. They are in essence the heart of the cell. If they malfunction, the cell loses vitality, and consequently the organ it forms becomes diseased.

How and why do the mitochondria malfunction?

The mitochondria of our cells can be compared to nuclear reactors in that both involve the capture of energy from atoms and its transformation to a useable form. In the cell, energy is released and captured in a stable form (a chemical called ATP) that can be later used to perform work. During energy production in the mitochondria, electrons are removed from specific molecules (food metabolites). Occasionally, a single electron escapes from the confines of the energy-producing machinery during this process and reacts with molecular oxygen to produce a highly reactive free radical, the superoxide radical. This free radical, if not removed or neutralized, will damage the cell. The cell contains a specific enzyme, superoxide dismutase (SOD), that corrals the radical and converts it to hydrogen peroxide. However, the detoxification mission is not complete, since hydrogen peroxide can also be converted to toxic free radicals by reaction with certain common metals present in the cell. The cell has additional enzymes, including one known as catalase, capable of converting the hydrogen peroxide to harmless water and molecular oxygen.

There is evidence that although these two free radical detoxification enzymes (SOD and catalase) are present in the cell, their quantity may not be quite enough to eliminate all the free radical species before they damage cellular components. This mechanism is what inspired Denham Harman to propose one of the more popular theories of aging, the Free Radical Theory of Aging. As these escaped radicals react with and distort our cells, the organs they comprise begin to gradually deteriorate, resulting in age-associated appearance – wrinkles, for example – as well as disease.

Recent support for the Free Radical Theory of Aging

As mentioned at the outset, the investigators who studied catalase worked with animals that were genetically manipulated to produce excess catalase. Otherwise the animals were perfectly normal in all respects (relative to their non-genetically manipulated counterparts) except for two important features. First, they lived longer. Second, perhaps more importantly, they demonstrated an attenuation of the severity of age-associated diseases including, arteriosclerosis, cardiomyopathy, and cataracts.

The scientists carried the work a step further to determine if the excess catalase produced by these animals was, in fact, acting to protect important cellular components from free radical damage. The investigators showed that a key enzyme in the cell required for energy production by the mitochondria, and known to be susceptible to free radical attack by hydrogen peroxide radicals, was much more active in the animals containing the super catalase gene, as compared to controls with normal catalase production. Furthermore, the investigators demonstrated the catalase over-producers had less age-associated damage to their DNA in skeletal muscle and heart cells. In general, the catalase appeared to be protecting the cell from free radical damage to multiple cellular components.

Why doesn’t the cell have more catalase to protect it from damaging free radicals?

One hypothesis is that free radicals may be important in early development in that they may promote cell division and increase the rate of development. It is interesting that in biological systems the emphasis is on propagation of the species and not so much on longevity. What may be good for rapid growth and protection of the animal until the age of reproduction may be detrimental to the organism in later years. Not a pleasant thought as it implies once we have reproduced ourselves, we are no longer needed for the good of our species.

On a more optimistic note, this seminal work provides significant evidence that mitochondrially generated free radicals are involved in aging and disease in mammals. It also supports a role for the potential power of antioxidants in protecting our cells and improving health and longevity.

This work also implies, however, that it is unlikely that one antioxidant, in this case catalase, is a “silver bullet” to promote longevity to a maximum. Even if it were, enzymes do not lend themselves to formulation as a tablet or capsule. During digestion, enzymes generally are transformed, rather than absorbed into the bloodstream in their active state; thus, they cannot be taken in pill form to increase cellular levels. To increase levels in humans, the enzyme would probably have to be inserted into our genome. This is not a likely scenario in the near future.

The body requires numerous antioxidants, all with specific missions. Catalase fulfills one of those missions, and it turns out to be a very important one, as it does result in a 20% increase in life span in animals. However, the human body is extraordinarily complex, and it is highly probable that a variety of antioxidants would have a more pronounced effect on cellular health and longevity.