Juvenon Health Journal volume 3 number 9 september 2004
By Benjamin V. Treadwell, Ph.D.
Where did I place the car keys? Deterioration in mental function with age occurs throughout the animal kingdom, but the degree of this deterioration varies between individuals of a species. There are some smart old mice as well as some smart old people. Why do we have this decline, and why do some have a sharper decline in mental function than others?
A recent study suggests some potential answers to this question. Post-mortem examination of the brains of elderly people with a neurodegenerative condition, as compared to the brains of elderly persons who had no such condition, demonstrated a significant increase in mutations in genes contained in a particular cellular structure responsible for energy production, the mitochondria. Specific types of mutations, those in the region involved in switching the gene on and off, were two-thirds more common in persons with a neurodegenerative condition.
The central nervous system, which includes the brain and spinal cord, requires more energy than any other tissue of the body, including muscle tissue (except during strenuous exercise). In fact, every day our brains require the equivalent of a quarter-pound of sugar to be converted into the chemical form of energy, ATP. If there is a deficit in ATP stores, the health of the brain deteriorates. Why? One reason is that structural components of the brain deteriorate with age. They must be disassembled and replaced, much like the components of an engine have to be periodically replaced to maintain a smooth-running machine. In fact, the youthful brain, compared to an older one, has more energy, and greater capacity to prevent damage to cellular structures, as well as to replace those that do get damaged. These and other activities performed by the brain take work, and ATP is the source of energy to run the cellular machinery.
The manifestation of a brain that is deficient in stores of energy (ATP) is impaired mental function – where did I place my keys? Parts of the body that require the highest amounts of energy, brain and muscle tissues, are in fact the most susceptible to deterioration during an energy failure. Therefore, it should be no surprise these two tissues are most affected by the aging process.
That brings us back to the original question, the connection between gene mutations in our mitochondria and the aging process. The mitochondria are the cell’s dynamos involved in converting food to the form of energy the cell can use, ATP. So anything that affects their function will affect ATP production. The mitochondria, like the cell’s nucleus, contain genes. (In a way, they are a cell within a cell). The genes of the mitochondria are switched on when the cell requires more energy. More ATP is then produced. A healthy, clear-thinking brain is the consequence. If one or more of the genes of the mitochondria are mutated, the ATP-production switch will not be turned on, and an ATP deficit will occur – where did I place my keys?
The above description of age-associated mental decline is supportive of the major theory of aging, the mitochondrial theory of aging. Briefly, this theory proposes that symptoms of aging are the result of an accumulation of mutations to the genes of the mitochondria. Furthermore, the theory goes on to state that the source of the toxic substances that cause these mutations is the mitochondria. The toxic substances are oxidants or free radicals released during the production of energy.
Impairment of energy production or mitochondrial efficiency actually increases the production of toxic free radicals. So a mutated mitochondrial gene not only impairs energy production, but this in turn adds to the problem, namely an increase in the rate of toxic free-radical production. Secondly, the brain contains cells referred to as post-mitotic cells, because once the organ reaches maturity, its cells no longer divide (undergo mitosis). We are stuck with them for life. So if defects in the cell, including the mitochondrial defects, cannot be repaired, we are stuck with them too.
Multiple factors probably explain why some people have earlier decline in mental function. For example, gene profile has a profound effect on mental health. Some individuals may have genes that are more effective in producing potent antioxidant defense systems than others. A second factor is environmental. People exposed to environmental toxins, such as cigarette smoke and toxic chemicals, and/or who maintain a poor diet, are at a higher risk for early mental decline.
What, if anything, can be done to help prevent or slow down the process of mitochondrial deterioration?
Recent work from the laboratory of Bruce Ames, Chairman of the Juvenon Scientific Advisory Board, at the University of California, Berkeley, not yet published, provides additional insights pertinent to this story. Researchers fed aged rats a compound, acetyl-L-carnitine, for 4 weeks and examined the tissues of the brain for markers of aging. This compound, normally present in the mitochondria, but at lower levels as we age, was selected for this study as it was previously shown to improve mitochondrial function in aged rats.
One area of the brain known to be involved in spatial memory, the hippocampus, has been previously demonstrated to accumulate numerous age-associated oxidation products. As expected, the oxidized products were present in increased quantities in the old animals Ames was studying. The oxidation products include oxidized proteins, lipids, and – more relevant to today’s topic – oxidized or mutated DNA. Examination of the brains of aged rats maintained on a diet containing acetyl-L-carnitine for 4 weeks revealed a significant decrease in the quantity of oxidized protein, lipid and more importantly, DNA. These results suggest that this compound may be of value in helping to maintain healthy brain tissue as we age, and thus mitigating age-associated decline in mental acuity.
Much more work is required before one can extrapolate these results to humans. Nevertheless, a number of earlier studies with humans have suggested a role for acetyl-L-carnitine as an agent that helps maintain healthy nervous system tissue.
What are the differences at the cellular level between a healthy aging brain and one that succumbs to disease? A recent study looked at mutations in mitochondrial DNA in the regions that control gene expression. Diseased brains had significantly higher levels of disease-specific mutations, which support the theory that mutations of mitochondrial DNA contribute to the development of disease. For technical details, click 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 about Juvenon™ Cellular Health Supplement
QUESTION: Now that I have taken Juvenon for almost a year, how can I tell that it has helped keep my mitochondria healthy? Is there a test I can take to actually see the difference?
E.W., via email
ANSWER: The Juvenon™ Cellular Health Supplement formula has been demonstrated to maintain healthy structure, function and efficiency of mitochondria in animal studies. Proof comes from autopsy of liver cells following the death of the animal. To demonstrate the effect in your own cells (since you’re not ready for autopsy!) is more challenging.
The clinical features of improved mitochondrial function are increased energy level and improved mental function. Normally, people notice an effect within 3-4 weeks, but not all have the same effect. It is more intense in some and less noticeable to others. There is evidence, again from animal studies, that the compounds in the Formula do help protect DNA, RNA, protein and lipids in cells. Juvenon is conducting both clinical and pre-clinical studies to advance understanding of mitochondrial function.
Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon’s Scientific Advisory Board.