Juvenon Health Journal volume 7 number 11 november 2008
By Benjamin V. Treadwell, Ph.D.
Though many of us may not want to hear it, there is mounting evidence to support the health benefits of burning those excess calories stored in various parts of our bodies as fat. Interestingly, there appears to be a correlation between where the fat is stored and how detrimental it is. Fat stored internally around organs, as well as externally at the waistline, seems to do more damage.So, if storing fat, instead of burning or metabolizing it, is generally unhealthy and, as a consequence, shortens our lives, why does the body do it?Imagine a built-in biological mechanism that begins ticking at conception and continues at a healthy rate through our fertile years. This “clock” slows as our ability to reproduce declines and so does our health. It’s an evolutionary process, favoring survival of the species over the individual. A recent study of fat metabolism in a tiny worm, the nematode C. elegans, may help explain.More Fat, More Offspring
Researchers, at Massachusetts General Hospital and Harvard Medical School, wanted to demonstrate just how fat metabolism, reproduction and aging interact. Aware of previous work, by other laboratories, that had already established the connection, they set out to answer the question: why and how would increased fat storage in cells decrease lifespan, but increase an organism’s capacity to produce offspring?Their organism, the nematode C. elegans, revealed some interesting answers at a biochemical level. The investigators found that precursors of gametes (sperm and egg), known as germline stem cells (GSC), produce hormone-like substances that, in turn, act to inhibit specific genes. The genes control certain biochemical pathways, one of which is the insulin-signaling pathway.
Inhibiting these genes results in an increase in fat storage, a corresponding decrease in fat metabolism in specific cells, and a decrease in the longevity of the worm. But why would reproductive cells increase fat stores, decrease fat-burning and shorten lifespan?
Reproduction requires a significant amount of energy for the development of the oocyte (egg). It seems logical that the GSC would have some control over the supply of fuel for the production of the necessary energy and that a biological system evolved to assure enough fuel was stored.
Unfortunately, C. elegans evolution seems to be directed toward keeping the gamete-carrying organism alive and healthy only long enough to reproduce itself. However, when the researchers removed (or inactivated) the GSC from one group of worms, they lived significantly longer than their counterparts with germline stem cells.
How Worm-like Are We?
Mammals also have genes, analogous to the nematode, that control metabolic pathways involved in the conversion of food to fat which will be utilized as an energy reserve. In the worm, for example, one of the longevity genes inhibited due to GSC is called daf-16. In humans, this gene is similar to the FOXO gene. (See Juvenon Health Journal Volume 7, No. 9, September 2008, “The Mystery of Longevity: a clue from DNA.”)
It seems clear, from studies and medical records, that an increase in fat storage in humans is associated with health concerns like diabetes and cardiovascular conditions. In other words, an overabundance of stored fat translates to a shorter lifespan for both human and nematode.
What is not known, however, is whether removing or inactivating the germline stem cells in humans would have the same life-extending effect as that observed with C. elegans. (And how many of us are willing to be sterilized to find out?)
Tipping The Balance
Happily, we may not have to choose between a longer life and the ability to reproduce. Reducing caloric intake can also activate the genes involved in the metabolism of fat and its conversion to energy, so that fat stores are depleted.
The positive effects of caloric restriction on increasing lifespan, as well as improving overall health, have been documented in virtually all species tested, including mammals. There is also some preliminary evidence that certain plant-derived compounds, such as resveratrol, may activate the genes and metabolic pathways to convert fat to energy, while inhibiting the genes that trigger fat storage.
Of course, there are a number of other factors that influenceour health, as well as how long we live, including our genetic constitution (See Juvenon Health Journal issue previously referenced). The lifestyle we choose to follow also plays a significant part.
A healthy diet, low in high-density caloric foods (sugar- and fat-loaded “junk” foods) and high in low-density caloric foods (vegetables, fruits, berries and whole grains), can have a dramatic effect on fat metabolism and overall health. Furthermore, regular exercise helps promote the conversion of fat to energy to deplete excess fat stores.
So, although there is no magic bullet currently available that has been proven to promote a longer, healthier life in humans, we can improve our chances without sacrificing survival of the species.
A group of investigators at Massachusetts General Hospital (MGH) and Harvard Medical School, Boston, MA, recently pursued a better understanding of the relationship between fat metabolism, reproduction and aging, proposing to determine the biochemical connection between them. The results of their study were reported in ”Fat Metabolism Links Germline Stem Cells and Longevity in C. elegans,” in the November 7, 2008 issue of Sciencemagazine.
The MGH/Harvard research evolved from an interesting observation that had been demonstrated in a popular model of aging the nematode,C. elegans, as well the fly, D. melanogaster. The earlier investigators noted that germline stem cells (those cells that differentiate into gametes, sperm and egg) produce signals that amplify aging. The MGH/Harvard scientists set out to determine exactly how the signals promoted aging, specifically in the nematode.
The results of the MGH/Harvard study showed that the germline-produced signals acted on and inhibited specific genes involved in fat metabolism. Those genes were necessary for the conversion of stored fat, contained in fat cells of the intestine, to free fatty acids which would be utilized (burned) for energy production.
The MGH/Harvard scientists concluded that fat metabolism is linked to reproduction and aging, and that the latter is accelerated if the conversion of fat to energy is inhibited. Their work also shed light on the actual mechanism involved in genes that have been previously linked to aging.
Although there are many similarities between nematode and human, authors of this study stopped short of extrapolating their findings to higher forms of life. Definitively linking germline stem cell signals to fat storage and accelerated aging in mammals, including humans, requires further research.
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: I was wondering if any research has been done with the product in regards to whether it increases glutathione levels. There seems to be a lot of interest in products that raise glutathione levels. It would be great if it could be proven that Juvenon does, indeed, increase them. Thanks for your time. – T
answer: There is significant animal and cell culture evidence that glutathione (GSH) increases in cells exposed to the active compounds in Juvenon. However, scientists have yet to demonstrate that our cellular health supplement raises levels of this antioxidant in humans.
Because we do know that GSH levels decline with age, you may want to talk with your health professional about taking Q-Veratrol along with Juvenon. We recently introduced this new supplement, which contains GSH-boosting N-acetylcysteine, as well as other cell-protective nutrients.
Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon’s Scientific Advisory Board.