Juvenon Health Journal volume 9 number 1 january 2010
By Benjamin V. Treadwell, Ph.D.
Is it possible to extend lifespan? Although it hasn’t been proven for humans yet, the answer seems to be yes, at least for yeast, flies, mice and, according to recent research, primates. When it comes to how, the theories continue to evolve, including some fascinating recent studies, which supply key information to support not only the belief that life (including human) can be extended, but also that health conditions associated with aging can be ameliorated.
20-plus Years of Data
In the mouse and rat, for example, plant-derived compounds have been shown to increase lifespan, as well as decrease the incidence of certain diseases. These compounds were discovered after an exhaustive search for a nutrient that mimicked, at the cellular level, the more established lifespan-extending effects of dietary/caloric restriction (DR).
For over two decades, studies of animals, maintained for various periods of time on DR (30-40% fewer calories than they normally consume per day), have yielded an enormous amount of information. This data has given scientists clues to the mechanics of DR at the cellular and sub-cellular level, implicating several key biochemical pathways, which seem to be altered by DR to elicit its positive biological effects. (For more on the benefits of dietary/caloric restriction, see Juvenon Health Journal, Volume 7, Cellular Housecleaning: The Anti-Aging Benefits and Healthier Aging: Clues From The Youthful Liver of an Aging Mouse and Volume 8, Optimizing Your Health: From Refresher Course to Recent Findings.)
Food or Family
Of course, there’s more to lifespan than what an animal eats or doesn’t. Some people, born with certain genetic constitutions, do seem to have an edge on longevity. In fact, the theory that longevity runs in families has been substantiated at the genetic level (See Juvenon Health Journal, Volume 7, Mystery of Longevity: Clue from DNA.) Although genes are important, environmental factors are at least as important. Which brings us back to the quantity and quality of food consumed.
Most of us don’t have to be reminded that a nutritionally balanced diet – fruits, berries, vegetables and legumes with additional protein from fish and, occasionally, some lean red meat – is better for us. Studies only recently support the complementary recommendation to minimize calories for a longer, healthier life. But how, exactly, does dietary/caloric restriction (DR) affect health and longevity?
Testing a Popular Hypothesis
One interesting result of DR, in addition to lifespan extension, is a significant decrease in fecundity (ability to reproduce). Numerous hypotheses have been put forth to explain the phenomenon. According to the most accepted (to date), the DR animal activates or inactivates one or more biological pathways to direct one or more nutrients, now in short supply, from non-life-essential functions, such as reproduction, to those critical for the survival of the organism (energy production, etc.).
The consensus may be changing, however. A group of investigators, well respected for their contributions to our current knowledge of longevity, recently conducted a study designed to prove or disprove the nutrient reallocation theory.
The team used an established model for aging studies, Drosophila melanogaster (those tiny flies that buzz around the fruit in your kitchen) and its simple yeast diet. With the premise that fecundity and longevity are mutually exclusive, the researchers added back different nutrients (fats, carbohydrates, vitamins, and amino acids from a protein digest), one by one, to the diets of separate groups of fruit flies maintained on DR. The objective was to determine whether/which nutrients were key to increasing the fecundity rate to the level common in flies fed a full diet.
Pinpointing an Amino Acid
Only the flies on amino acid-enriched diets showed the increase in fecundity. So, the next question was whether any of the 20 amino acids that regulate fecundity would elicit this effect or just those that must be obtained from diet, as our bodies can’t make them – the 10 essential amino acids (EAAs).
The researchers discovered that the EAAs were responsible. In fact, they were somewhat surprised to find that adding back only one EAA, methionine, to the restricted diet restored fecundity to the fully fed animal level. Furthermore, they observed that those flies fed the methionine-supplemented DR diet not only had normal fecundity, but also lived the extended lifespan of their counterparts maintained on unmodified DR.
So, in the case of these fruit flies, longevity and fecundity were not mutually exclusive. This suggests that reallocation of nutrients, the popular theory, does not explain the responses to dietary restriction.
Not Too Much Menthionine
But is more methionine, alone, the key element in increasing longevity and/or fecundity? Apparently not. The experiments indicated that excess methionine may interact with one or more of the other EAAs to cause a toxic effect. (In fact, recent research has demonstrated that mice fed a diet low in methionine live longer.)
The investigators extrapolated that the critical piece is the ratio of the 10 amino acids to one another. An imbalance in one, such as too much methionine, relative to the other nine, can negatively affect important biological pathways, actually resulting in shortened lifespan as well as impaired health.
To Be Continued
This topic is so exciting and complex that it will also be the subject of the next Juvenon Health Journal. We will delve a little deeper into the new studies and the cellular mechanisms affected by dietary restriction, such as autophagy, a self-digesting pathway that may promote a healthy balance of amino acids (the ideal ratio of methionine to the other EAAs), and how this is integrated with other pathways, such as those under insulin regulation.
Aging research is rapidly advancing, with indications that longevity and accompanying health can be significantly affected by environmental factors such as diet. This author believes it won’t be long before a specific regimen can be prescribed to help us live longer, healthier lives. Until then, results like those discussed here support maintaining a generally nutritionally balanced diet.
Three investigators from University College London recently published “Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila” in the international scientific weekly,Nature. They reported on studies they performed with the fruit fly, regarding the importance of amino acids in determining lifespan and fecundity (measured by egg-laying capacity).
The researchers designed an experiment to test the popular hypothesis purported to explain the increase in lifespan in flies under restricted dietary conditions (DR). According to that theory, the organisms have an innate capacity to reallocate nutrients from non-essential tissues (such as reproductive organs), to more life-sustaining critical functions, such as energy production for maintenance of the body. (Supporting evidence was derived, in part, from the fact that DR flies show reduced fecundity.)
To test the hypothesis, the investigators separately fed a variety of nutrients – including carbohydrates, lipids, vitamins, and amino acids – to several cohorts of DR flies. The results demonstrated that only intake of essential amino acids, not calories, had an effect on fecundity, returning it to the level found in fully fed flies. Taking the study a step further, the team attempted to determine whether one or more of the essential amino acids elicited this effect. They found that, in fact, only methionine was required.
The researchers also found, to their surprise, that DR flies supplemented with just methionine not only had fecundity equivalent to that of fully fed flies but, by contrast, also maintained the longer lifespan associated with DR. This was not the case, however, when the other eight essential amino acids were added back in with the methionine. Although the flies still had normal fecundity, their lifespan decreased to that of the fully fed flies.
The above results do not seem to support the popular DR hypothesis. The team observed that increased intake of calories per se does not reduce lifespan. Longer lifespan does not appear to be a function of reallocation of nutrients (amino acids) from non-essential organs (reproductive), to life-sustaining functions (energy production). Rather, it appears the effects of DR are related to the balance between methionine and the other essential amino acids.
Read summary 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 read your article recommending supplementing our diet with alpha lipoic acid. Why? Our bodies produce it naturally. – cheers, C
answer: You are correct. Our bodies do produce both lipoic acid and L-carnitine. However, as we get older, and/or when we’re under stress, the cells of the body produce less than optimal amounts. Because the body does make them, these nutrients are not vitamins by definition. But they are often referred to as “conditionally essential nutrients” – under conditions of age and stress, we need to supplement the body’s supply.
Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor.