Anti-Aging Solution: Less Food or More Nutrients?

Juvenon Health Journal volume 8 number 8 august 2009
By Benjamin V. Treadwell, Ph.D.

I, for one, take little comfort in the recommendation to “age gracefully.” Is that really the only respectable action we can take when faced with the seemingly inevitable decline in mental and physical activity as we get older? Or is there evidence that we may be able to slow-down, possibly even reverse, some of those uninvited changes?

Eating Less to Live Younger
Research has long reinforced the connection between eating less, or caloric restriction, and living healthier, longer. Experiments, dating back to the early 1900s, showed that rats lived significantly longer when fed one-third less calories per day than they normally consumed.

“What’s the connection between eating less and living healthier, longer?”

These caloric restriction (CR) findings seem to have stayed on the back burner for quite a while. Then, about 20 years ago, several studies demonstrated that CR’s health benefits occur at the cellular level, affecting biochemical pathways involved in energy production and helping to promote a healthy, balanced metabolism and immune system.

Human studies have also associated caloric restriction with positive changes in important health markers, for example, decreased LDL cholesterol and a corresponding increase in HDL (good cholesterol), as well as decreases in markers of inflammation (TNF alpha, IL-6, CRP), which have been associated with cancer, atherosclerosis, heart disease, diabetes and neurodegenerative disease. (See our Volume 8, 2/09 Health Journal for more information on caloric restriction.)

Caloric Restriction Works, But Why
So, scientists had demonstrated that certain biochemical pathways were altered by a diet radically lower in calories, with significant health benefits. Yet, a central question remained: why?

Investigators have only recently found that CR alters certain genetic pathways, too. Research results, published just a few months ago by a team from the University of Wisconsin, not only offer a more complete explanation, but also suggest an alternative to food deprivation.

Altered Genes
Working with 25-month-old (aged) and five-month-old (juvenile) mice, the investigators first examined five specific genes in two organs, the heart and brain. They found the genes were altered (mostly activated) in the older animals.

“Investigators have only recently found that CR alters genetic pathways.”

(Interesting aside: Most of the age-altered genes produced cellular bi-products that are linked with metabolic pathways involved in inflammation. As mentioned earlier, in human studies, published by a number of laboratories, these inflammatory markers have been associated with many age-related disease states.)

The next logical question? Would caloric restriction somehow act on these same genes to restore their youthful activity level?

Hungry Genes
To find out, the team designed an experiment with two groups of five-month-old mice. One (controls) was offered all they could eat. The other (CRs) was given 25% less of what the control group ate. The mice were kept on the diets for 20 months, until they reached old age, when gene transcripts (RNA) were extracted from heart and brain tissues.

“CR appears to improve cellular health and prevent aging by altering gene activity.”

Using a bioassay technique, known as DNA microarrays, the investigators measured gene activity, i.e., the amount of RNA transcripts produced. Relative to juvenile animals, the control group showed an increase in gene (inflammatory) expression. The gene profile of the 25-month-old CR group, on the other hand, was virtually the same as that of juvenile animals. In other words, CR appears to improve cellular health and prevent aging by altering gene activity.

Supplemented Genes
Now, the team expanded their research. Drawing a parallel to the CR-like health benefits attributed to certain plant-derived compounds, like resveratrol, the investigators theorized that specific dietary nutrients could also alter gene expression.

With another mouse model experiment, they tested eight nutrients with antioxidant properties – lipoic acid, acetyl-L-carnitine, CoQ10, resveratrol, curcumin, lycopene, astaxantin (a carotenoid), and tempol (a synthetic antioxidant) – as potential CR mimetics.

This time, the mice were all offered the non-CR diet, but they were separated into groups, each receiving a different supplement with the food. Once again, the gene activity was measured with heart- and brain-extracted RNA.

The results? The nutrients did mimic caloric restriction, stopping and reversing the gene activity associated with aging, at least in this mouse model.

“A cocktail of nutrients seems to be necessary, each functioning on different organs.”

More specifically, the diets containing lycopene, resveratrol, tempol or acetyl-L-carnitine were as effective as CR in maintaining youthful gene expression in heart tissue. Mice on a diet supplemented with lipoic acid or CoQ10 showed youthful gene expression in the brain (cerebellum). The antioxidants curcumin and astaxantin also elicited positive effects on many of the aging markers in the heart and the brain.

Powerful Knowledge
To summarize, these researchers learned that aging involves altered gene expression and reducing caloric intake can stop or reverse progression to an aged gene expression profile. Perhaps most intriguing are their discoveries that certain (particularly plant-derived) nutrients can substitute for caloric restriction in promoting/protecting a youthful gene profile, and that a cocktail of nutrients appears to be necessary as each seems to function on different organ systems.

With the advent of more advanced (faster) techniques to screen potential compounds, future research should provide invaluable information on aging intervention options that are not as unappealing, but as effective as caloric restriction.

“Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants,” recently published in Aging Cell, offers some interesting new findings related to the molecular basis of aging and expression of biochemical markers.

Researchers from the Universities of Wisconsin and Alabama used DNA microarrays to identify panels of transcriptional markers of aging in multiple strains of young (five months) and old (25 months) mice. They studied five genes in the heart and five in the brain (cerebellum) throughout the animals’ life spans and were able to demonstrate expression of gene products common to all strains. (Interestingly, the majority were involved in inflammation.)

With this basis, the investigators constructed one experiment to determine the effects on gene expression of one of the only established anti-aging therapeutics, caloric restriction (CR). The results demonstrated that feeding the animals a CR diet did, indeed, have a positive effect. The levels of the five gene products returned to those present in young animals.

A second experiment was designed to establish whether certain antioxidant nutrients could produce a similar effect. Different groups of mice were fed a regular (not CR) diet, supplemented by one of several nutrients, from youth through old age. These results were also positive, with some of the antioxidants maintaining a youthful gene expression in old animals.

Of, perhaps, greater interest, were the tissue-specific effects of the nutrients. Some antioxidants had a more pronounced effect on gene expression in the heart, others in the brain.

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 about Juvenon™ Cellular Health Supplement.

question: A Juvenon subscriber asked you, in the last newsletter, if his energy level might increase if he were to take an extra Juvenon tablet. You replied that it was possible, but that he should take the third, extra tablet six hours, minimum, before bedtime. Why is that? What is the optimum time to take these pills? I know they should be taken on an empty stomach but would like more info. – J 

answer: There is evidence that taking the Juvenon supplement too close to bedtime can interfere with sleep, although this side effect may not occur with everyone. The biochemical explanation involves the neurotransmitter, acetylcholine, levels of which normally decline with age. This neurotransmitter is important for memory and compounds in Juvenon enhance its production. However, increasing acetylcholine levels just before sleep may interrupt memory consolidation during sleep, which may also interfere with the normal sleep pattern.

Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor