Читать книгу The Principles and Practice of Antiaging Medicine for the Clinical Physician - Dr. Vincent C. Giampapa - Страница 18

Wear-and-Tear Theory The wear-and-tear theory of aging was originally presented by Dr. August Weismann, a German biologist. This theory focused on the fact that the body and its cells are damaged by overuse and abuse; that is, the specific organs are worn down by toxins in diet and in the environment. Most specifically, Dr. Weismann’s theory focused on the detrimental consumption of fat, sugar, caffeine and alcohol, as well as the harmful effects of the sun’s ultraviolet rays. The wear-and-tear process is not confined to our organs; it also takes place at the cellular level.

Neuroendocrine Theory of Aging Developed by Vladimir Dilman, Ph.D., a Russian research scientist, this theory elaborated on the wear-and-tear theory by focusing more specifically on the neuroendocrine system. Dr. Dilman’s concept of aging focused on the complicated network of biochemicals that controls the release of hormones and, therefore, regulates other vital body functions. Dr. Dilman stated that during youth, “our hormones work together to regulate many bodily functions, including our responses to stress from the environment, as well as changes in our diet and mental state.” Dr. Dilman further stated that “the hypothalamus governs the release of key hormones that regulate virtually all organs in the body through a complex series of chain reactions.” According to this theory, the hormones are vital for repairing and regulating body functions, and when aging causes a drop in these key hormone productions, it alters the body’s ability to repair and regenerate itself as well. Most important, Dr. Dilman stressed how hormone production is highly interactive: that is, the drop in the production of any one of the hormones will probably have a feedback effect on the whole mechanism, signaling other organs to alter their release of hormones as well. In essence, the neuroendocrine system is like a symphony, irreparably ruined by discord of any one instrument. Because of Dr. Dilman’s theory, the concept of hormone replacement remains a key component of any anti-aging treatment.

Genetic Control Theory of Anti-Aging According to this theory, obsolescence is programmed into our genes and therefore encoded in our DNA. The theory is that everyone is born with a unique genetic code and a fixed predisposition to certain types of age-related diseases. It stresses that genetic inheritance has the preponderance of effects on how quickly a person ages and how long a person lives. It is a deterministic theory, comparing humans to a machine that is preprogrammed to self-destruct. As a result of this theory, anti-aging medicine concepts began to stress the importance of supplying the building blocks of DNA within each cell. Although many aspects of this theory have been supported by research on DNA, the one of complete determinism by a preprogrammed set of genetic sequences has been shown not to be completely true. What is true, is that we inherit genetic tendencies, not genetic certainties.

Free Radical Theory of Anti-Aging Originally introduced by Dr. Gershchman in 1954, this theory was further expanded by Dr. Denham Harman of the University of Nebraska College of Medicine. A free radical is any molecule that differs from conventional molecules in that it possesses a free electron. This property makes it react with other molecules in a highly volatile and destructive way. In a conventional molecule, the electrical charges are balanced. Electrons normally reside in pairs so that electrical charges can neutralize each other. Atoms that are missing electrons combine with atoms that have extra electrons, therefore creating a stable molecule with evenly paired electrons, and the result is a neutral electrical charge.

A free radical, however, has an extra electron, creating a negative (−) charge. Because of this unbalanced electrical energy, the free radical tends to attach itself to other molecules in order to obtain a matching electron and attain electrical equilibrium. Some scientists speak of the free radicals as “thieves,” which break up the normal pairing of electrons in neighboring molecules in order to steal a new electron for themselves. This leads to the creation of more free radicals and extensive body damage mainly to the cell membranes, as well as to genetic material. Free radicals, however, are important as a normal aspect of healthy body status: without free radical activity, the body would not be able to produce energy, maintain immunity, use hormones or even contract muscles. This electrical production within the body enables the body to perform these key functions. This key quantity of electricity comes from the unbalanced electron activity of free radicals.

The most significant targets of free radical damage are cell membranes, DNA and RNA. Damage to nuclear DNA can result in faulty copies during cell reproduction and damage to mitochondrial DNA; this in turn results in a decrease in energy production, which is essential for running the nuclear genetic machinery necessary to make proteins, enzymes and even hormones.

Free radical damage begins at birth and continues until death. Early in life, its effects are relatively minor because the body has extensive repair and replacement mechanisms in place that allow the cells and organs to work optimally. Over time, however, the accumulative effects of free radical damage begin to take their toll.

Cosmetic surgeons and physicians are used to seeing the effects of free radical damage on collagen and elastin, the substance that keeps skin smooth, moist, flexible and elastic. The most obvious effects of free radical damage occur in the skin in the forms of deep wrinkles, loss of elastic properties of muscle and a decrease in the content of facial fat.

One of the key components of anti-aging therapy is to prescribe and create a host of natural and manufactured antioxidants to help combat the effects of aging. The body possesses an inherent ability to produce intrinsic antioxidants, the most common ones being superoxide dismutase, catalase and glutathione peroxidase. These are produced and stored mainly at the intracellular level of the mitochondria, which is another key focus of anti-aging therapy.

Waste Accumulation Theory According to this theory, cells produce more waste than they can properly dispose of. This waste may include many different toxins, which accumulate in the cell and therefore interfere with normal cell function, ultimately killing the cells. Results of a great deal of new research support this theory, especially with regard to the production of a waste product called lipofuscin. This compound is frequently found in the nerve and heart cells. Lipofuscin is formed by a complex reaction that binds fat and proteins within the cells.

Membrane Hypothesis of Aging^2,3 A recent elaboration on the waste accumulation theory is this hypothesis (Diagram II-2), which was popularized by Dr. Imre Zs-Nagy.² In this theory, free radicals damage the cell membrane, and it becomes unable to let nutrients in and waste products out. Waste products focused on in this theory include lipofuscin and cellular salts in the form of potassium, which build up within the cell, causing the cell to become dehydrated. This interferes with the normal flow of electrolytes in and out of the cell, allowing the toxins and the cell’s metabolic waste products to accumulate and eventually cause the death of the cell. This theory also accounts for the effects seen in aging resulting from a loss of hydration in both the facial skin and body skin. This is discussed further in Chapter VII, on skin and aging.

“Limited Number of Cell Division” Theory According to this theory, the number of cell divisions is directly affected by the accumulation of the cells’ waste products. The more waste that is accumulated within our cells, the faster these cells degenerate.

This theory was originally proposed by Dr. Alexis Carroll, a French surgeon who was able to keep two chicken hearts alive in saline solution for over 28 years. He believed he had achieved this by disposing of the waste products within the cell. The theory was discounted by Dr. Leonard Hayflick when it was found that fresh cells had inadvertently been added to the cultures, making the chicken heart cells seem immortal.

Hayflick Limit Theory In 1961, two cell biologists, Dr. Morehead and Dr. Leonard Hayflick, made one of the most important contributions to aging theories. Dr. Hayflick¹ theorized that the aging process was controlled by a biological clock contained within each living cell. In his research, he studied human fibroblast cells from the lung, skin, muscle and heart and found them to have a limited life span: they divided approximately 50 times over a period of years and then suddenly stopped.

Nutrition seemed to have an effect on the number of cell divisions. Whereas overfed cells made up to 50 divisions in a year, underfed cells took up to three times as long as normal (or overfed) cells to make the same number of divisions. This information was to be used as the basis of research in the future on caloric restriction and life extension, in general.

Death Hormone Theory Dr. Donner Denckle, an endocrinologist, formerly of Harvard University, originally presented this theory. He was convinced that the “death hormone,” or decreasing oxygen consumption hormone (DECO), released by the pituitary gland, contributed to the loss of neurons in the brain. When he removed the pituitary glands of rats, their immune systems were revitalized, the rate of crosslinking or glycation in the cells was reduced and cardiovascular function was restored to much more youthful levels. Denckle speculated that as humans age, the pituitary cells begin to release this “death hormone,” which inhibits the ability of cells to use the thyroid hormone (thyroxin). This affects the basic metabolic rates of cells to convert food to energy, and the resulting changes in the metabolic rate bring on and accelerate the process of aging.

Thymic Stimulating Theory According to this theory, the thymus gland is the master gland of the immune function. Dr. Alan Goldstein, Chairman of the Biochemistry Department of George Washington University, popularized this theory. The size of the thymus gland itself continues to shrink from birth to death. Studies have shown that thymic factors are helpful in restoring the immune function, as well as in rejuvenating poorly functioning immune systems in both old and young patients. Thymic hormones probably play a role in stimulating and controlling the production of neurotransmitters and key hormones that affect brain function, which therefore affects central pacemakers of aging.

Mitochondria Theory of Aging This theory is similar to the free radical theory, in general, and stresses the fact that free radicals directly damage mitochondrial DNA. Mitochondria are the energy-producing organelles (subcellular units or micro organs) within the cells that are responsible for producing adenosine triphosphate (ATP), which is the primary source of cellular energy.⁴ ATP fuels the nuclear and mitochondrial genetic machinery to allow cell reproduction to occur. At the same mitochondrial location, cells produce energy but also produce the vast amounts of potentially damaging free radicals. Mitochondria, because they have limited or very poor DNA repair mechanisms, are an extremely sensitive target for free radical damage.

Errors and Repair Theory In 1963, Dr. Leslie Orgel, of the Salk Institute, suggested that because the machinery for making proteins in cells is so essential to life, an error in this genetic machinery could be catastrophic. He focused on the production and reproduction of DNA and stated, “Over time this is not carried out with accuracy.” Because the body’s protective mechanisms to restore DNA are poor from birth on and decrease in number and efficacy with age, this repair system is incapable of making perfect repairs on damaged DNA, and this results directly in disease and other age-related changes. This theory seems to have gained credibility, specifically in reference to the more recent research and literature documenting the importance of DNA repair.^5–8

Identical DNA Theory This theory suggests that there are genetically identical “sequences of DNA within our genetic codes that take over after the initial sequences are worn out or damaged. Dr. Medvedev, at the National Institutes of Medical Research in London, proposed that in different species, life span may be a function of the degree of these repeated genetic sequences in the nucleus.

Crosslinkage Theory of Aging This theory was initially proposed in 1942 by “Johann Bjorksten. The crosslinking phenomenon, he stated, “occurs in neighboring molecules, and as we age, the number of crosslinks increases, causing, for instance, skin to shrink and collagen to become less soft and pliable.” He proposed that these crosslinks begin to obstruct the passage of nutrients and waste products between cells. He also proposed that the immune system is incapable of cleaning out this excess crosslinked material, which is found in a specific form of glucose molecules. These glucose molecules react with proteins, causing further crosslinking and the subsequent formation of destructive free radicals. His research has caused more recent anti-aging scientists to focus on the importance of glycation as a key component of the aging process.

Autoimmune Theory According to this theory, as the body ages, the body’s ability to produce necessary antibodies to fight key diseases declines. In another sense, the immune system also becomes self-destructive and reacts against its own proteins. More recent literature has lent credibility to this theory, especially in view of the effects of the aging gastrointestinal tract and leaky gut syndrome (LGS). LGS has been shown to be directly related to the autoimmune phenomenon as people age.

Caloric Restriction Theory This theory was originally proposed by renowned gerontologist Dr. Roy Walford, of the University of California, Los Angeles, Medical School, who stated, “Undernutrition without malnutrition can dramatically retard the functional as well as the chronological aging process.” Although Dr. Walford could not explain the underlying biological processes, he stated that “cutting caloric restriction had a direct effect on obtaining maximum health and life span.” He stressed the importance of not only caloric restriction but also moderate vitamin and mineral supplement intake, coupled with regular exercise. The discovery of the Sir2P gene has verified the importance of such supplements and exercise.

Gene Mutation Theory In the 1940s, scientists investigated the role of mutations in aging. Mutations are changes that occur in the genetic structure of DNA. Genes are critical for every aspect of cellular life. In experiments with radiation, it was observed that radiation not only increased animals’ genetic mutation but also accelerated the aging process.

Rate of Living Theory This theory was originally proposed by a German physiologist, Max Rudner, who discovered the relationship among metabolic rate, body size and longevity. He first introduced the theory in 1908 and stated simply that “We are each born with a limited amount of ‘energy.’ When we use this ‘energy’ slowly, our rate of aging is slowed. If the energy is used quickly, aging is hastened.”

Telomerase Theory of Aging According to this theory, the one most recently proposed, aging is based on a specific sequence of base pairs located at the end of each chromosome. The end portion of a chromosome is called a telomere. This information was first discovered by a group of scientists at Geron Corporation of Menlo Park, California. It was observed that telomeres were sequences of base pairs extending from the ends of the chromosomes. They maintain the integrity of chromosomes during cell division. Every time a cell divides, telomeres are shortened and more distal to the end of the chromosome. This occurs until the cell stops dividing and, eventually, dies. Scientists discovered that the key element in rebuilding disappearing telomeres is the immortalizing enzyme called telomerase. This is an enzyme found only in germ cells, cancer cells and another cell group now known as stem cells. Telomerase appears to repair and replace telomeres, restoring them to a less distal position on the chromosome and thereby manipulating the clock mechanism that controls cellular aging.