The Methylation Control of Gene Activation and Silencing Theory
According to Dr. Stanley Burzynski, adult cells in the body have an established methylation pattern in their DNA that is essential to the aging program. But Dr. Burzynski also states that in the very first days of life this methylation pattern is erased. Most genes in our DNA are active during the initial embryonal development. Then they begin to become blocked through methylation as their expression is no longer needed. Many genes are silenced in this manner after birth, including the one for hemoglobin F (Fetal Hemoglobin). This trend accelerates especially after age 25 with increasing numbers of genes silenced as we grow older. If for any reason the silencing affects tumor suppressor genes, the aging person may develop cancer. Continuous silencing of genes in the aging bodies is a major factor leading to progressive aging and ultimately death. Dr. Burzynski has isolated a number of substances that can reactivate these tumor suppressor genes in cancer patients as well as reactivate other genes that are involved in symptomatic aspects of aging. He has termed these molecular switches antineoplastons. While activating tumor “suppressor genes to help alleviate the potential cancer, these antineoplastons “also “turn on” other genes, which can provide aging patients with a number of benefits. Therefore, Dr. Burzynski believes it is realistic to contemplate that we may be able to stop and reverse the pattern of methylation that occurs in normal aging by using properly designed molecules to act as “switches” that deactivate certain genes and activate more youthful genes.
Unified DNA Damage Theory of Aging (UDDTA)
After a review of all these theories of aging, it becomes obvious that there are many different concepts, which can affect aging and many overlaps among these theories.
The new theory which I have conceptualized over the last decade and which I now describe focuses on a combination of these theories. This theory stresses that the basis of control for the aging process in cells lies in the accurate reproduction of DNA and its resulting essential products—stem cells. DNA is essential for life, because it is directly responsible for every molecular change occurring within the body. Damage is inflicted on DNA every day by the environment, diet and both physical and emotional stress that humans endure. This damage is the primary cause of aging and diseased states. As bodies age, people become more susceptible to many serious diseases. The most common age-related diseases today in the United States that cause death are heart disease, stroke, cancer and Alzheimer’s disease. But what causes these diseases and how do they start? In essence, they can all be traced back to the initial breakdown of, and damage to, DNA.
In this theory, both the rate and quality of DNA damage most likely triggers key genetic control processes like methylation and therefore are responsible for changing gene profiles as we advance from fetus through childhood, adolescence, adulthood and old age.
The importance of a healthy state of DNA cannot be overemphasized. Within each human body, there are an estimated 100 trillion cells. Within each of these cells is approximately 5 feet of DNA. That means there are billions of miles of DNA within each human body. Just improving a small percentage of this extraordinary and vast amount of genetic material can make a major difference in the quality of health, well-being and how a person ages.
In essence, DNA is “life’s blueprint,” or, in more focused terms of this discussion, “aging software.” An individual code for health and life expectancy is genetically passed on to each person. It is inherited by each person from his or her parents, grandparents and so forth. New research has documented that life spans in both animals and humans are directly correlated with DNA repair rates.6,9
Throughout life, DNA reproduces and replaces itself continually. In optimal conditions, DNA copies itself over and over again, making perfect reproductions. This is very close to the state that people are in when they are young and healthy. As people age, however, their DNA is damaged continually through ongoing bombardment by excess free radicals, environmental effects and radiation. The DNA begins to reproduce poorly and ultimately stops reproducing completely, which results in cell death.
Think of it as making a photocopy. If a well-maintained machine is used to copy the original document, it produces an excellent copy. But if the machine is poorly maintained, it will ultimately produce poor copies. Furthermore, if the machine continues to make poor copies of poor copies, the degradation becomes worse and worse with each successive copying cycle until eventually the copies are illegible. In essence, the same thing happens with DNA. If the body cannot produce clean and accurate copies of its DNA, health and longevity are directly affected. Therefore, the key to optimal health is to keep DNA clean and healthy so that it produces ideal, clean copies of itself. Currently, this can be done by helping the body neutralize excess free radicals and, at the same time, strengthen and nourish cells and the building blocks for DNA.
New literature has documented that even in old people, the telomeres (the sequence of base pairs at the end of our chromosomes) that seem to control the number of cell divisions have still not reached their terminal positions, which should signal final cell death.10 In essence, humans have not reached their full genetic potential, which is stored in each cell.
According to this new theory, humans are not irreversibly programmed to age and die, as is currently thought; in contrast, humans are programmed for self-repair and longevity. The key to optimal health, therefore, is the ability to keep DNA healthy in order to produce, ultimately, as clean a cell copy as is possible. This new theory is referred to as the unified DNA damage theory of aging (UDDTA).
The essential concepts in this new theory emphasize the ability to improve the ratio of DNA repair to DNA damage. This ratio of repair to damage is much higher early in life, when DNA repair can easily neutralize the damage sustained by DNA. In both nonprimate mammals and primates, it has been shown that the greater the DNA repair levels are, the longer the life span is.6 As animals age, this ratio becomes inverse, and the damage rates overcome the DNA repair capabilities. This inversion of the ratio of DNA repair to damage is linked directly to a number of key processes that are encoded within genes (see Diagram II-1). These processes, as mentioned in Chapter I, are glycation, inflammation, oxidation and methylation. The origin of these chemical processes lies within the genetic blueprints, the DNA. During the aging process, they slowly become uncontrolled, and each reaction contributes to further damage produced by the others. In essence, the loss of balance in this aging equation is responsible for altering the ratio of DNA repair to DNA damage. The loss of the subsequent accurate copies of DNA and the damage to the enzymes responsible for the DNA repair are the causes of the age-related changes that are seen in the form of both the microscopic and macroscopic effects on the body.
Furthermore, the damage to DNA has a direct impact on another key component that is responsible for aging: stem cell pool reserves. Adult stem cells have been shown to be present in many different body tissues, including adipose tissue, neuronal tissue, immune tissue and gastrointestinal tissue. Adult stem cells have the potential to redifferentiate and restore the aging and nonfunctioning tissues that are damaged by the many aspects of aging itself. With continued damage and poor repair of DNA, the genetic machinery in the DNA of stem cells is also injured, and its regenerative and restorative capacities are therefore lost over time10 (Diagram II-3).
In summary, the key goal of anti-aging therapy should be to accomplish the following:
1.