Juvenon Health Journal volume 10 number 2 february 2011
By Benjamin V. Treadwell, Ph.D.
The good news about aging: we gain knowledge that can improve our lives and help our younger, more naïve friends avoid the pitfalls we’ve encountered. The bad news: the various organs of our body don’t function as well as they once did. We lose strength, endurance and, perhaps most disturbingly, the capacity to think as clearly and quickly, not to mention remember.
As you may recall, our last Health Journal (Volume 10, Number 1, “Aging Brain Health: Rediscovering the Energy Alternatives”) focused on the elderly brain, its energy requirements and cognitive function. This issue looks at the brain from a different perspective, the correlation between memory impairment and the documented, age-associated decline in brain size. Recent research indicates more good news here. We may be able to attenuate the slope of this decline.
Smaller Brain Smaller Veins
The latter decades of life have a profound effect on brain shrinkage with a loss of volume, in specific areas, of 1-2% or more per year. Among those affected the most? The hippocampus. This structure, especially its anterior region, is associated with memory, specifically spatial memory, which is important not only in cognition, but also to how aware we are of things happening around us. (As an example of spatial memory, consider a rat going through a maze to obtain a food reward. Spatial memory will help the rat find its way at a much faster rate on subsequent trials.)
Why would this part of the brain be so susceptible to the loss of volume in the aging process? A reasonable answer may be related to the significant energy expended by the hippocampus to run the cellular machinery necessary for thought. It seems logical that a small decline in energy supply, the consequence of shrinking veins that supply the nutrients, would not only affect our capacity to think with speed, but also the overall health of the hippocampus cells.
Related research grew out of the observation that those who are physically fit also seem to be mentally fit. Various animal studies tested the hypothesis that aerobic exercise, in elderly rats, would improve both physical and mental performance.
A number of articles have reported on the results: a significant improvement in the rats’ brain function, especially memory, as well as energy level. (See Juvenon Health Journals, Volume 3, Number 6, “Aerobic Exercise, Robust Body and Mind,” Volume 5, Number 5, “Moderate Exercise, the Elixir of Mental Health,” and Volume 7, Number 10, “Endurance Exercise: Keeping the Mitochondria Furnaces Burning.”)
Additionally, the animal studies revealed exercise-associated changes in the physical structure of the brain, including a healthier, more youthful appearance. One of these studies also demonstrated an increase in blood (serum) levels of a brain-derived neurotrophic factor (BDNF), which stimulates the growth of neurons in the brain. Another showed an exercise-induced increase in the brain’s vasculature.
As promising as these results are, however, the studies were performed on animals. (As one investigator’s son asked, “Do we really want smarter rats?”) Could similar results be documented in humans?
Exercise Wheel to Treadmill
A group of investigators recently designed an experiment to evaluate the effects of moderate aerobic exercise on the volume of specific areas in the elderly human brain, as well as on memory. This fascinating study involved 120 subjects, ages 55 to 80 (mean age 66).
The subjects were divided into two groups of 60. The experimental group exercised on a treadmill three times per week for 40 minutes per day at an intensity of 60 to 75% of their maximum heart rate. The control group did stretching exercises on the same schedule.
Before the start of the one-year experiment, participants underwent MRIs to measure the volume of specific areas of the brain, with emphasis on the hippocampus, thalamus and caudate nucleus. This procedure was repeated at the six-month point and at the end of the study (12 months). Blood was drawn at the start and end of the study and analyzed for BDNF level. The subjects also took standard spatial memory tests before and after the study. (For more details on methodology, see this issue’s “Research Update.”)
Bigger, Better Brains
Aware of previous data indicating the elderly brain’s loss of 1-2% of the hippocampus’ volume per year, the research team was not surprised to observe similar numbers in their control group. What was unexpected? Hippocampus volume in the experimental subjects didn’t just remain unchanged, it increased by 2%. In other words, exercise seemed to do more than simply compensate for the deterioration associated with aging. It may have actually reversed it.
The end-of-study spatial memory tests also showed marked improvement in the experimental group. So, along with the increase in brain volume, there was an increase in brain function. Interestingly, the experimental subjects’ serum BDNF levels were also noticeably higher than their start-of-study baselines.
The results of this study, combined with previous animal studies, provide compelling evidence to suggest that aerobic exercise can improve our quality of life as we get older. The potential outcome, keeping the brain functioning, seems to be well worth the effort – just two hours of moderate exercise per week.
Even with these encouraging results, several unanswered questions remain. Specifically, what is the mechanism for the increase in hippocampus volume? The studies seem to suggest delivery of more oxygen and/or more nutrients with an increase in vasculature, as well as growth of neurons in the brain with higher levels of BDNF.
More generally, can the brain volume-protective benefits of exercise be enhanced with nutrients? For example, what would the effect be of supplementing with resveratrol, considering the compound’s potential for increasing blood circulation to the brain as well as its capacity to act as a mimetic of caloric restriction, which results in fat metabolism that produces neuro-protective ketones? (See Juvenon Health Journals, Volume 9, Number 4, “Resveratrol: New Evidence for a Human Health Benefit” and Volume 10, Number 1, “Aging Brain Health: Rediscovering the Energy Alternatives.”)
In any case, as we wait for investigators to further explore the why, as well as the how, of maintaining a more youthful brain, there seems to be little downside to a moderate aerobic exercise program. With the OK of your health professional, of course.
Dr. Treadwell answers your questions.
question: The Juvenon bottle tells you to take two tablets a day, but an article in the Saturday Evening PostNovember/December issue says you should take one, based on the dosage that is in each pill. What are your feelings on this compared to what it says on the bottle? No other health issues are involved. Thank you for your time in answering this. — J
answer: The directions on the Juvenon bottle are a general recommendation and, in fact, most people seem to find that taking two tablets per day, one at breakfast and one at lunch, produces the best results. We have had feedback, from a relatively small percentage of people taking the cellular health supplement, that one tablet is the optimum dose, while two makes them “too energetic.” I recommend you try one per day first, then increase your dosage to two and compare your response. Of course, it’s always a good idea to consult with your health professional before taking any supplement.
Dr. Benjamin V. Treadwell is a former Harvard Medical School professor.
Aware of previous animal study results, which demonstrated the impressive effects of aerobic exercise on brain function and structure, a research team from four universities — Pittsburgh, Illinois, Ohio State and Rice — undertook a human study. The results are the subject of “Exercise training increases size of hippocampus and improves memory,” recently published in theProceedings of the National Academy of Sciences (PNAS).
In the animal studies, the structure associated with spatial memory function, the hippocampus, was most affected. In humans, this area of the brain seems to be the most susceptible to functional decline as well as physical deterioration (atrophy). Certain neurodegenerative conditions, including Alzheimer’s, have been associated with this deterioration, especially in the anterior hippocampus (CA1 region).
With these factors in mind, the researchers designed a one-year experiment for 120 subjects between the ages of 55 and 80 (mean age 66 years), who were healthy and not on an exercise program. The subjects were randomly divided into two groups, 60 in the experimental group and 60 in the control group.
The experimentals were gradually introduced to an exercise program that included 40 minutes per day of walking on a treadmill at an intensity producing a heart rate of 60-75% of maximum. The controls were asked to perform stretching and toning exercises, which did not significantly increase heart rate.
Before the study’s start, at its midpoint (six months) and at the end, segmental brain volume was measured for each participant with an MRI. Blood was drawn at the beginning and end of the trial to quantify levels of brain-derived neurotrophic factor (BDNF), a mediator of neurogenesis. Standard tests to evaluate spatial memory were also administered at the beginning and end of the experiment.
The results were impressive: a significant average increase — 2% — in hippocampus volume for the experimental group. By contrast, the controls presented an average 1.4% decline, consistent with data for adults older than 50, which shows hippocampal volume shrinking 1-2% per year.
Serum BDNF levels also increased in the experimental group, but not in the controls, correlating with the increase in hippocampal volume. The spatial memory evaluations corresponded with the other results, demonstrating improvement in the experimentals, but deterioration in the controls.
All the results confirmed the research team’s predictions. Interestingly, they also found that aerobic exercise selectively increased the volume of the anterior hippocampus, which includes the dentate gyrus, where cell proliferation occurs. The investigators concluded that higher fitness levels are neuroprotective, even when aerobic exercise is started relatively late in life.
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.