Juvenon Health Journal volume 7 number 10 July 2014
By Benjamin V. Treadwell, Ph.D.
What immediately comes to mind when someone mentions exercise? Guilt? Rationalizing? (I’m still pretty healthy even though I don’t exercise. A lot of my friends don’t exercise and they seem healthy.) Of course, not everyone should run miles at a time or lift massive weights. But there is compelling evidence to support the significant health benefits, both physical and mental, from a daily regimen of exercise appropriate for you.
One form of exercise, endurance training, was the subject of a recent study at the Howard Hughes Medical Institute (HHMI) laboratory, located at Yale University School of medicine. For decades, scientists have known that physical activity like running and swimming, which increases heart rate and breathing, results in significant physiological changes or adaptations to improve muscle function. For the first time with living human subjects, research demonstrated another beneficial effect of this type of exercise.
What are the effects of endurance training on the mitochondria of muscle cells?
That is an important question that scientists have only recently answered. Prior to that, scientists knew that with endurance training, changes in muscle tissue might include increased production of new blood vessels and greater capacity of cells to store energy. Endurance training also increases sensitivity to insulin so that glucose, as fuel, can enter cells more readily. All of these changes are directed toward improving the delivery of nutrients and fuel to satisfy the increased energy demands of the exercising muscle.
Beyond better fuel delivery, earlier animal and in vitro (cell culture) studies revealed something intriguing—an increased capacity of the cells that comprise the working muscles to burn fuel, especially fat, and thus to convert that fuel into energy. Moreover, endurance-conditioned cells continue to burn fuel, including fat—even when at rest. But why?
Exercise initiates a series of complex biochemical events in the muscle cells. One of these, the production of a substance known as AMPK, activates a cellular tool called PGC-1 alpha. This tool, in turn, enters the control center of the cell, the nucleus, where it homes in on the on/off switches of specific genes to turn them on. The activated genes produce proteins required to construct new fuel-burning organelles, the mitochondria.
This explains why, as earlier research had shown, muscle cells isolated from an endurance-trained animal had a greater capacity to produce energy than cells isolated from a sedentary counterpart. Simply put, more exercise produced more mitochondria/cell “furnaces” for more energy to make the exercise easier. The effects of endurance training on the mitochondria of muscle cells was clearly beneficial.
Animals to Humans
The early studies laid the groundwork for the team at the HHMI lab at Yale. They wanted to determine whether the same or similar changes occurred with humans, in particular, the effect endurance exercise has on the mitochondria in our skeletal muscle. Faced with difficulties in applying the same techniques used with animals and cultured cells, the investigators realized a newly developed, non-invasive tool could yield similar information if applied to humans.
The technique involved using a magnetic resonance spectrometer (MRS). This technology can accurately measure the amount of a nutrient containing a tag (13C-acetate) that is metabolized in the energy-producing cycle (the Krebs cycle or TCA cycle).
Two groups of human subjects were chosen for the study. Seven healthy males of normal weight who exercised in running-based sports a minimum of four hours a week were in one group. The second group included eight males of similar age, weight and overall health, but who did not participate in endurance training.
Both groups were injected with the 13C-acetate nutrient. After a fixed period of time and under non-working (resting) conditions, the muscle of the right calf was scanned with the MRS instrument. Because the 13C-acetate is essentially converted to substances that are burned as fuel, the scans provided the investigators with information on the rate at which the tag was being metabolized (oxidized into other compounds during the production of energy) in the cell’s mitochondria.
More Fuel Burned Without More Work
The results showed 54% more fuel burned in the TCA cycle in the endurance-trained group as compared to the sedentary controls. Interestingly, this burned fuel did not represent an increase in the production of ATP, the cellular chemical utilized by the muscle to do work (contract muscle). The amount of measured ATP in both groups was virtually identical.
On the one hand, this is not too surprising as the measurements were taken at rest, when little muscle contraction is occurring and, therefore, little of the energy molecule, ATP, is necessary. But on the other hand, the normal coupled reaction between fuel-burning and ATP production seems to have been disrupted in the endurance-trained subjects. In other words, the muscle of the endurance-trained group was still burning more calories (released as heat and not converted to ATP), even while at rest.
Getting The Fat Out
Modern man/woman is exposed to excessive amounts of energy-rich foods. As a consequence, we are more likely to develop diabetes, heart disease and other age-related conditions. Previous animal and cell-culture studies have shown that exercise improves insulin sensitivity, guarding against insulin resistance, the precursor to diabetes.
The recent HHMI research gives us even more insight into the potential long-lasting effects and benefits of exercise, specifically in relation to the fat-laden cells, including muscle cells, that have been associated with many health concerns. Endurance exercise, as demonstrated by the Yale team, activates cellular tools. They, in turn, increase the production of the cellular fuel-burning machinery (mitochondria) necessary to remove excess fat from cells…even while we sleep.
A group of investigators from a number of Pacific institutions recently published, “FOXO3A genotype is strongly associated with human longevity,” in the Proceedings of the National Academy of Sciences (PNAS). They reported on their findings regarding a specific genetic variation of FOXO3A.
This gene was investigated as a possible link to human aging based on previous work with lower forms of life (worm and fly), which identified a gene that, when mutated, seemed to confer longer life on the organism. The longevity-associated gene is involved in the regulation of insulin signaling pathways. Known as DAF-16 in the worm C. elegans, it is the counterpart of the human gene, FOXO3A, also associated with metabolic pathways regulated by insulin signals.
The investigators hypothesized a correlation between a similar mutation in the human FOXO3A gene and longevity in humans. They set out to test their theory by examining the frequency of a mutation in FOXO3A in a population of Japanese-American men living in Hawaii.
The subjects were divided into two pools, those who died before the age of 81, mean age 79 years (402 subjects), and those who lived 95 years or longer (213 subjects). Genetic material (DNA) was extracted from the blood cells of both groups and the FOXO3A gene was examined for specific genetic variation (mutations known as SNP).
The results of the gene analysis established a strong association between a specific SNP and longevity. This would seem to indicate that, like the worm and fly genes, the FOXO3A gene is, at least partially, responsible for longer life.
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 friend claims that many people don’t even digest vitamins and that chewing up vitamins or using liquid vitamins is the only way to have effective delivery. This is his claim but I know of no data to support it. What is the most effective way to take Juvenon and other examples of Dr Bruce Ames’ supplements?– D
answer: Some people may find that taking vitamins in liquid form is more effective than tablet form. However, in general, tablets dissolve readily and should be absorbed as well, or almost as well, as a liquid. I suggest taking the tablets with water or juice. If you find it difficult to swallow a tablet, try taking it with a thicker drink, such as low-sodium tomato juice, or a food such as yogurt.
As to the most effective way and time to take the various Juvenon supplements, here’s what I recommend:
- Juvenon Cellular Health Supplement. Take one tablet at breakfast and a second at lunch.
- New Juvenon Resveratrol Supplement. Take one capsule at breakfast.
- Juvenon Multivitamin, Q-Veratrol, Calcium Magnesium, and Omega-3.
Take one tablet of each at breakfast and a second at dinner.
For more information about Dr. Bruce Ames’ supplements, click on the name of any supplement above.
Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon’s Scientific Advisory Board.