By Benjamin V. Treadwell, Ph.D.

Ponce de Leon may have been closer than he knew to discovering the fountain of youth. Little did he realize the plants surrounding the pool were a more likely source for the mysterious potion he was so desirous of discovering.

It turns out that certain plants contain compounds that, when consumed by mammals, including humans, activate genes to produce enzymes. The newly synthesized enzymes function to protect our tissues from toxic substances. Unfortunately, as we age these enzymes lose their potency. Consequently, tissue-damaging attacks by the toxic compounds occur more frequently. The damage accumulates, resulting in age-associated diseases and related disorders. In essence, these substances, referred to as Phase II enzymes, help keep our bodies youth-like, full of bounce, flexible, mentally sharp and more resistant to disease. As we age, however, we require more of the compounds to restore the detoxifying enzymes.

As with the fountain of youth, this too sounds too good to be true, but some surprising discoveries described below may make you a believer. Our cells have a defense system far more sophisticated than anything the Pentagon has devised.

The cells composing our tissues are equipped with an early warning system - specific sensors that detect toxic chemicals produced by our bodies, as well as toxic compounds present in our environment (free radicals, pesticides, carcinogens). A very sensitive and recently discovered sensor molecule, Keap1, is present in the cytoplasm of most cells. This molecule contains a large amount of one particular amino acid, cysteine. Toxic substances (carcinogens) known as electrophiles (electron-loving) are attracted to cysteines. For the carcinogen, it is a fatal attraction.

Keap1 is the seductive secret agent that lures unsuspecting toxic electrophiles into its grasp. This specialized cellular molecule is a defensive protein. When toxic substances attack its cysteines, it releases a hidden defensive weapon residing within the Keap1 structure. The released compound known as Nrf2, functions as a sentry. It immediately scrambles to the nucleus of the cell to alert the cell's control center. After considerable cross-talk among components of the nucleus, Nrf2 is commanded to bind to a specific segment of DNA carrying a pre-designed counter-attack plan to neutralize the electrophilic carcinogens.

Nrf2 attaches to a specific segment of DNA, designated the "antioxidant response element" (ARE). ARE can be envisioned as the commanding general, who controls the activity of over 200 genes involved in defense of the cell. The sentry notifies ARE of the specific threat. ARE in turn activates one or more of its 200 genes to manufacture weapons (enzymes) to destroy the invading electrophiles.

Why is it necessary to have such a large arsenal of diverse weapons? Each of the 200 enzymes is designed for a specific duty to neutralize one of the numerous electrophiles lurking in our cells and present in our environment. It would be foolish for the cell to activate all 200, as this is not energy-efficient, and only a few are necessary for detoxification of a particular electrophile. Each electrophile carries with it a signature picked up by the sentry, and carried to the nuclear control center, which then decides what message to send to "General" ARE. ARE, in turn, activates the most specific and effective defense, requiring the minimum energy expenditure necessary for victory.

What are these plants and other compounds?

Many compounds capable of inducing this system of Phase II enzymes are plant-derived, including substances in broccoli, the spice turmeric, and garlic. The plant- and animal-derived antioxidant alpha lipoic acid (ALA) also has this ability, as shown in recently published results. Minute quantities of ALA are available in many of the foods we consume, such as spinach, but the most available source of ALA is as a dietary supplement.

One of the Phase II enzymes recently demonstrated to be induced by lipoic acid is involved in the production of the vital antioxidant, glutathione. This antioxidant is critical for the detoxifying activity of several additional Phase II enzymes, as well as acting directly to protect the cell from oxidative damage.

Ironically, glutathione decreases in our tissues as we age, while oxidative stress increases with age. Just when we need the greatest amount of protection from oxidants, we produce this important antioxidant in diminished amounts. This decrease in glutathione-synthesizing machinery is, in turn, the result of a decrease in the cellular levels of the antioxidant gene activator, Nrf2. Therefore, as we age, we need more Nrf2 to help restore a healthy level of glutathione.

How can we improve this condition? Scientists have learned that if they feed an inducer of Phase II enzymes - broccoli extract, turmeric, garlic, or lipoic acid - to laboratory animals, the Nrf2 is released from the confines of Keap1. In effect, this increases the level of this Phase II activator by preventing its destruction.

As a consequence of feeding animals one of the Phase II inducers, the liver and other organs of old animals have as much protection from oxidants as those of a younger animal. The inducer increases levels of Nrf2 which, in turn, promotes the elevation in glutathione levels as well as other protective antioxidant enzymes.

Since it has been demonstrated that the plant compounds mentioned above, and perhaps more effectively lipoic acid, can restore cellular Nrf2 and glutathione of old animals to levels characteristic of younger animals, it is reasonable to predict that this same diet is likely to promote healthy cells in aging humans as well.

Before ending, I must acknowledge one of the major pioneers in this area of research. Until recently, the mechanism for the activation of Phase II enzymes, also referred to as detoxification enzymes, was poorly understood. The individual responsible for much of the pioneering work unraveling the mysteries of this detoxification system is Paul Talalay from the Johns Hopkins School of Medicine. An octogenarian, he continues to be a major contributor to this area of research. I don't know, but I suspect his good health and active mind may be partially attributed to a diet replete with Phase II-inducing compounds which, thanks to his work, have proven to be less elusive than Ponce de Leon's legendary quest.

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.

QUESTION: Since taking Juvenon, I feel I've been sleeping more soundly, but not always. How does Juvenon affect sleep?
J.M., via email

ANSWER: Although Juvenon™ Cellular Health Supplement promotes deeper sleep if taken well before bedtime, it can inhibit your ability to fall asleep if you take it too late in your day. In brief, the explanation has to do with the way the compound affects neurotransmitters in the brain. I would take one tablet with breakfast and a second one with lunch or no later than 6 hours before bedtime.*

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Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon's Scientific Advisory Board.