Younger-Acting Cells: A Balance to Clear the Way

Juvenon Health Journal volume 9 number 5 – May 2010
By Benjamin V. Treadwell, Ph.D.

Imagine driving in city traffic. The lights are timed so that, if you’re lucky and there aren’t any accidents or crazy drivers cutting in front of you, you can drive several blocks before a red light stops you. But realistically, multiple factors often throw the system off balance and the traffic rarely flows smoothly. You, and other frustrated motorists, find yourselves sitting through several light changes before moving. This situation is similar to what goes on in our cells.

“Autophagy (literally ‘self-eating’) is a process by which the cell ‘cleans house’.”

“Vehicles” (proteins and other molecules) travel to and from various areas of the cell. They have destinations that are specifically directed to alter activity in response to a demand placed on the cell. For example, there are specialized machines (enzymes) that recognize when there is an excess of nutrients (protein, fat, sugar) in the cell and, in turn, activate certain hormones, such as insulin. Insulin then travels through the blood stream to turn on metabolic pathways (anabolic), which for the most part, results in protein and fat synthesis and sugar storage.

Ideally the cellular system is balanced: the amount of nutrients taken in via diet is largely expended in the form of energy to keep us moving, thinking and healthy. However, the metabolic balance can be upset by excess nutrient intake, potentially leading to unhealthy conditions, particularly those associated with aging.

Can we facilitate metabolic balance, in other words, smooth cellular traffic? Let’s take a closer look at the processes and possibilities.

No Cellular Road Blocks
Old and damaged cellular machines can interfere with smooth cellular traffic. But there is a process, autophagy (literally “self-eating”), by which the cell “cleans house,” removing the old material and replacing it with new machines that function optimally. Recent work has demonstrated the importance of this activity in maintaining cellular health via metabolic balance.

“Fasting seems to stimulate autophagy and lead to a healthier cell.”

In fact, this process starts, for the first time, at birth, when the cells of the body require high nutrition, but have little available for the first several hours. To supply this nutrition, the newborn’s cells digest damaged cellular organelles into their constituent components – amino acids, fats, nucleic acids and carbohydrates. Some of these building blocks are used to construct new healthy organelles, while some are converted to the energy needed for the reconstruction.

More Food, Less Autophagy
So, autophagy is a lifelong cellular process. But it does not always function at an optimal level. Recent evidence, from a number of different groups of investigators, has demonstrated that excess food intake, for example, diminishes autophagy, with a related increase in health concerns and decrease in lifespan.

On the other hand, fasting or restricting one’s caloric intake appears to have the opposite effect. It seems to act as a kind of “body cleanser,” stimulating autophagy and leading to a healthier cell. (Aside: intriguing that many religious groups encourage fasting at certain times of the year).

Perhaps the answer lies between these two extremes: a highly nutritious diet, with just enough calories and specific nutrients to maintain an active autophagic system and sufficient vitamins and nutrients to maintain an otherwise healthy, toxin-free cell. Which leads us to the next question…

More Spermidine, More Autophagy
What are the specific nutrients capable of regulating autophagy? The results of a recent study, reported by a group of researchers in Europe and California, point to a polyamine. The investigators describe the effects of feeding the fruit fly, Drosophila melanogaster, the nematode, C. elegans, and yeast a diet containing spermidine, a compound made by human cells but in decreasing amounts as we age. (This may be a contributing factor to aging.)

“The spermidine-fed cells had a longer lifespan than non-treated cells.”

The organisms fed the spermidine-supplemented diet lived longer. The researchers concluded that this was due, at least in part, to an increase in autophagic activity. They extended their study to human cells grown in culture and the results were consistent: the spermidine-fed cells had a longer lifespan than non-treated cells. In related experiments, other investigators demonstrated that mice fed spermidine lived longer, with less disease, than their non-supplemented counterparts.

The mechanism involved appears to be inhibition of an enzyme (histone acetyl transferase or HAT) that alters chromosome structure, preventing the activation of some genes, while promoting the activation of the genes responsible for autophagy. (Another plant-derived compound, resveratrol, seems to have a similar effect on stimulating autophagy, but this may be via another mechanism, activation of an enzyme that changes chromosomal DNA structure by removing acetylated chromatin.)

One additional possibility (not mentioned by the authors of this study), with regard to how spermidine elicits its positive health effects, may be activation of a metabolic pathway that depletes the amino acid methionine. As described in two previous Juvenon Health Journal articles (See Volume 9, Balanced Diet: Fine-Tuning For A Longer Lifespan and Dietary Restriction: Getting More From Your Mitochondria.), decreasing levels of certain amino acids can function as a caloric restriction mimetic.

“The goal is metabolic balance for toxin-free, younger-acting cells.”

But back to spermidine. A fermented soybean product, Natto, is one of the foods that contains the highest concentration of the nutrient. Interestingly, it is consumed by 77% of the people in Japan and the Japanese have some of the longest lifespans in the world. Whether Natto is one of their longevity secrets remains to be determined. Other foods high in polyamines are soybeans, green pepper and grapefruit (Perhaps another reason for weight reduction associated with grapefruit consumption? See Juvenon Health Journal Volume 8, Plant-Rich Diet: Why Let It Grow On You?.)

More Research, Better Balance
And back to the study outlined above. Although it’s exciting, further studies, including human trials, are needed before we all jump on the polyamine bandwagon. The goal, after all, is metabolic balance. Too little or too much of one or more nutrients can upset the balance, potentially creating unhealthy conditions instead of toxin-free, younger-acting cells.

The polyamines, putrescine, spermine and spermidine, have been implicated in the regulation of different cellular biochemical events, such as binding to and altering the structure and function of DNA and messenger RNA and turning on and off specific genes. Very recently, a new function has been ascribed to spermidine: activating autophagy, cellular events that result in the increased lifespan of several organisms (yeast, the fruit fly, and the nematode C. elegans).

This discovery and the research behind it (which also showed that spermidine improves the replicative lifespan of human cells in culture) were the subject of “Induction of autophagy by spermidine promotes longevity,” published in Nature Cell Biology. The authors, from research institutes and universities in Austria, California, France, Greece, Scotland and Switzerland, examined the mechanism involved.

They found that spermidine inhibits the chromatin-modifying enzyme histone acetyltransferase (HAT). Their work demonstrated that this event resulted in a differential effect on the regulation of a number of genes. More importantly, spermidine stimulated transcription of those genes, coding for specific factors involved in the activation of the autophagic pathway.

Autophagy entails the transport of defective cellular organelles to the lysosome, where they are dissembled into their constituent building blocks – amino acids, fats, carbohydrates and nucleic acids. These are then utilized for construction of new organelles as well as for the production of energy. Recycling old/defective cellular organelles into new, healthier and more functional replacements improves the health, as well as increases the lifespan, of the organism.

The investigators concluded that, by stimulating this process, a spermidine-supplemented diet increased longevity. Their work supports previous studies with mice that demonstrated an increase in lifespan and a decrease in age-associated pathologies in mice fed a polyamine-supplemented diet.

Read abstract here.

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.

Dr.Treadwell answers your questions.

question: I have ordered Juvenon tablets for the first time. My father, who is 84, is also considering ordering Juvenon. I have four questions:
1) I am 32 years old. Does it make sense to take Juvenon at my age (as an anti-aging preventative, for example)?
2) How long does it take to realize any effects?
3) Other than price, is there any difference between taking Juvenon tablets or capsules?
4) My father also takes several medications. Could adding Juvenon cause problems?
Thank you very much for your help. – 

answer: Good questions, S, as you and, hopefully, your father start taking Juvenon. The answers follow by corresponding number.
1) There are many people below age 40, some in their late teens, who take Juvenon Cellular Health Supplements. The results/benefits can vary, however, depending on several factors, including weight, physical condition, level of stress (both physical and mental) and gene profile.
2) It usually takes about three weeks, on average, to experience the effects of Juvenon. However, the amount of time varies from person to person. Many have felt a difference in energy level in a week, while for some, it has taken up to six weeks to notice any benefits.
3) Both capsules and tablets contain the same active compounds, but I prefer the capsules for three reasons. They’re smaller, which makes them easier to swallow. Because they dissolve more rapidly and the powdered nutrients are easier to digest, the capsule form is faster-acting. And they contain only two excipients (ingredient stabilizers), while the tablets require more.
4) To date, there have been no reports of negative effects from taking the Juvenon Cellular Health Supplement as well as any drug, vitamin or herb. However, it’s always a good idea to consult with your health professional to be on the safe side.

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