By Benjamin V. Treadwell, Ph.D.

Wouldn't it be nice to wine and dine on mouth-watering, high-fat foods, and still maintain a healthy cardiovascular system, as well as a sharp mind? And maybe live longer as well? Research data indicate this is exactly what the French are able to do. The French are known for their high intake of fatty foods and for wine consumption. Yet the incidence of heart disease in France is 40% lower than predicted for their high-fat diet.

The French Paradox and Red Wine

Research to explain this phenomenon, dubbed "The French Paradox," focuses on a particular component in wine, particularly red wine. Research has led to some fascinating discoveries and perhaps to a more profound understanding of the aging process and how it may be manipulated to increase life expectancy.

It has been suspected for some time that chemicals in wine function as antioxidants, helping to protect the cardiovascular system from inflammation-induced oxidative damage. These compounds, called polyphenols, are known to contain potent antioxidant properties. However, what is even more exciting is that one of the polyphenolic compounds present in wine has the capacity to mimic the only known method of prolonging life in creatures from yeast to mammals, and probably humans. That method is caloric restriction (CR).

In the 1930's it was discovered that the life of a rat could be extended by 30-40% by restricting the number of calories it consumed. The life-extending property of caloric restriction was later demonstrated to be effective in extending the lives of lower forms of life including yeast, worms, and flies. More recent studies, using the lowly yeast because of its short life span, examined at the molecular level how such a diet promotes life extension.

The research led to the discovery of a specific gene, known as SIR-2 (silent information regulator) that is necessary for CR-induced longevity. Yeast lacking or containing a defective SIR-2 gene did not live longer when they were fed a CR diet. The SIR-2 gene or variations of it were recently found to be "evolutionarily conserved," as is evident from their presence in yeast, as well as in multi-cellular organisms, such as worms, fruit flies and mammals (including humans!).

What does this gene do? In short, it contains the genetic blueprint for production of enzymes (protein deacetylases) that act on specific cellular proteins to alter their structure, and consequently their function. As cells age, errors accumulate, and the DNA becomes disorganized and unstable. One result of this gene's action is the conversion of a volatile, flimsy DNA, to a more compact, stable DNA. A compact DNA structure has less chance of getting reshuffled and losing specific genes in the process…like cards mysteriously lost by a cardsharp reshuffling a deck of cards. For example, yeast lacking SIR-2 do not respond to CR by compacting their DNA. Instead, they meet an early death as a consequence of DNA reshuffling and the shedding of DNA fragments that self-replicate to toxic levels.

Whether this event occurs in humans is yet to be determined, but the data are tantalizing. It is known that proteins present in our cells are affected by a related human enzyme known as SIRT1. This enzyme inhibits a protein (p53 tumor suppressor) that, under certain stress-related conditions, initiates a form of cell suicide, known as apoptosis. One can theorize, therefore, that life could be extended if the SIRT1 enzyme can deactivate this suicide protein.

Does this mean no pain, no gain? Do we have to suffer cellular stress in order to live longer? Not necessarily, and this is where wine enters the story.

Scientists decided to see if this gene product could be activated by other methods, such as by specific chemical compounds that mimic CR. After a vigorous search they discovered a class of plant-derived compounds, commonly referred to as polyphenols, capable of activating the SIR-2 enzyme. The plant sources containing these compounds include green tea, red onions, apples, red wine, and others.

The most potent of the polyphenolic compounds in activating this enzyme is present in highest levels in the skin of grapes, especially grapes grown in nutrient deprived soil, and/or infected by fungi. The compound is known as resveratrol and is produced by the grape in response to environmental stress, such as dehydration, UV radiation, soil deficient in nutrients, and infection by certain pathogens. Scientists found that when they isolated this compound and fed it to yeast and other organisms, including worms and the fruit fly, it extended life span approximately 30-70%. This was amazing, since the life of these creatures was extended without the pain of CR. Resveratrol substituted for CR not only in activating the SIR-2 enzyme, but also in extending life.

A general theory (xenohormesis hypothesis) was recently put forth to help explain this phenomenon. It states that plants produce these polyphenolic compounds in response to stress. The stress-induced compounds in turn promote cell survival by altering metabolism to conserve cellular energy and protect vital cellular components until the stress is eliminated. An extension of the theory states that animals that eat the stressed plants containing these compounds, will in turn benefit from a life-preserving effect on their cells. Researchers are currently scrambling to determine if this class of compounds, the polyphenolic compounds like resveratrol, can extend the life of mammals including humans. Maybe we can have our cake and eat it too!

But there is more to the story. The initial research was directed at learning more about why the French have unusually good cardiovascular health in spite of their high-fat diet. It develops, however, that additional human health benefits, besides cardio protection, have been reported for plant polyphenols. These include cancer inhibition and protection of the nervous system. One can envision two modes of action by polyphenols in providing cellular health. First, they function as antioxidants and prevent free radical damage to cellular molecules, including proteins. Second, by activating the SIR-2 enzyme, they stabilize DNA weakened by free radical-damaged proteins that accumulate with age. Hence they prevent cell death.

For now, the message seems to be, enjoy that glass of red wine and cheer on the scientists who are inexorably unmasking the mysteries of human health and longevity.

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: A recent "Ask Ben" column featured a question about not experiencing any effects from taking 2 Juvenon per day for four months. You answered, "You might want to test taking a third tablet during the day to see if you feel an effect. I do that on occasion and find a significant boost in energy, especially mental alertness." Since you feel significantly better on three, why do you not take three every day? What if you took four tablets a day and felt even better? If one took four tablets per day for an extensive period and found them helpful, would one's body and brain then have trouble getting along on only two per day?
J.A., via email

ANSWER: You raise some interesting questions. I have personally found that taking more (3-4 per day) does increase energy, but I have also found that when I go back to 2 per day I seem to get the same amount of energy. It appears that the body doesn't develop a tolerance to the compounds, but it requires different amounts for saturation, depending on diet, activity level and gene constitution.

People do not seem to develop a tolerance to the Juvenon formula. If you take 4 per day for several months, it should not change the effect you felt initially at 2 per day if you return to that dose. Some of us may obtain a greater effect by cycling between 2 per day and 3-4 per day on occasion.

Thank you for your feedback, I really do appreciate it.

Send your questions to AskBen@juvenon.com.
For more questions and answers, go to juvenon.com/product/qa.htm.

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