lthough many of the factors involved in human aging still remain a mystery, our understanding of the aging process has advanced significantly over the past few decades. This article provides an overview of some of the leading theories of aging, with a particular focus on their implications regarding life extension.

In researching this article, I spoke with Ward Dean, MD, and Arthur Balin, MD - two experts on human aging - to find out what they think the primary causes of aging are and what they think can be done to stop, slow down, or reverse the aging process. Dr. Dean is the medical director of the Center for BioGerontology in Pensacola, Florida, and is the author or coauthor of a number of popular books, including Biological Aging Measurement and Smart Drugs & Nutrients. Dr. Balin was the executive director of the American Association of Aging and is the author of such influential books as Human Biologic Age Determination and The Life of the Skin.

In general, current theories of aging can be separated into two basic groups. One group suggests that aging is caused primarily by the accumulation of DNA damage due to the wear and tear caused by free radicals. When genes are this damaged, they can no longer adequately control the functions of cells. The other group centers around the notion that aging is built into our DNA from the start and is a direct consequence of our genetic programming.

DNA Damage Theories

THE FREE RADICAL/OXIDATION THEORY OF AGING
Probably the most influential of current theories, the free radical/oxidation theory of aging is supported by a large and growing body of evidence. Developed by Dr. Denham Harman in 1956, the theory postulates that changes due to aging are caused by free radical reactions. Free radicals are atoms or molecules that contain at least one unpaired electron. This makes the molecules chemically unstable and allows them to react easily with other compounds in the body. In so doing, free radicals and other reactive oxidants can cause extensive damage to cells and tissues, impairing the immune system and leading to infections and various degenerative disorders, such as cardiovascular disease. Perhaps worst of all, they can damage the DNA in our cells and put us at risk for cancer.

Many researchers believe that the havoc that free radicals and other reactive oxidants wreak on our bodies is the basis for the aging process. It has been shown that accumulation of free radical damage increases with age.¹ Support for the free radical theory of aging has increased progressively over the years, and growing numbers of studies implicate free radical reactions in the pathogenesis of specific diseases, such as cancer and arteriosclerosis.²

Free radicals can be caused by exposure to radiation and toxic chemicals, but they also result from seemingly harmless and necessary metabolic processes, such as the breakdown of stored fat molecules for use as an energy source, or simply from metabolizing oxygen. Sun exposure can cause the generation of free radicals too. An effective antioxidant regimen would include a well-designed multivitamin/multimineral antioxidant formulation. A booster formulation containing added amounts of Vitamin C and E, and various flavonoids would also be useful for additional protection. Polyphenols such as are found in green tea can add yet another important range of protection.

DNA DAMAGE AND REPAIR THEORY OF AGING
Oxidative damages to DNA are among the best documented and most prevalent of DNA injuries and are likely to be a prominent cause of aging. (This theory is similar to the free radical/oxidation theory, with more emphasis placed on direct DNA damage and repair.) DNA is particularly sensitive to oxidative damage, and breakages occur continuously in the cells of living organisms. While most of these damages are quickly repaired, some accumulate, because the DNA repair mechanisms cannot correct defects as fast as they are produced.

Many researchers suspect that the overall aging of the organism is caused by these accumulated genetic alterations, which inhibit the cells' ability to function properly and can lead to their death.¹

An example of a substance that does direct damage to DNA, hydrogen peroxide is considered to be one of the most dangerous oxidants, because it easily diffuses through cell membranes and can injure the delicate biological machinery. High concentrations of hydrogen peroxide can lead to cell death and even lower concentrations that can cause permanent genetic alterations. This DNA damage could lead to mutations and ultimately to the malignant transformation of cells (carcinogenesis).

Bulletin: Confirmation of Free Radical Theory Just in. As we go to press, an important article has just appeared in Science magazine that may fundamentally alter our knowledge about the different theories of aging.6 Authored by Dr. Richard Weindruch (whose work has found caloric restriction to extend life in animals) and three other researchers, the Science article shows that certain antiaging genes, which repair damage caused by free radicals, are significantly reduced in their activity in animals on high caloric diets, as compared with animals on low caloric diets (calorically restricted diets). According to research scientist Dr. Raj Sohal of Southern Methodist University, the study "helps confirm that the formation of free radicals are at the heart of aging, and that gives us ways to seek out medicines that may prevent free radical damage."7 This is very exciting. It should now be possible to rapidly determine the best protocols for slowing the aging process, given that many of the antiaging genes have now been identified. And the evidence thus far points to genes that repair free radical damage.

MITOCHONDRIAL DNA THEORY OF AGING
This theory, also originated by Denham Harman, proposes that the accumulation of mitochondrial mutations during life is an important contributor to both the aging process and to several human degenerative diseases. (This theory is distinguished by its emphasis on mitochondrial damage and repair.) The mitochondria - a specialized part of cells that are responsible for producing the energy within cells - have their own genetic material (mtDNA), which is distinct from the nuclear DNA in the cell. The mtDNA is produced at the inner mitochondrial membrane, near the sites where free radicals are formed. Mitochondrial DNA appears unable to counteract the damage inflicted by these free radicals (byproducts of respiration) because, unlike the nuclear DNA, they lack advanced repair mechanisms.

Oxidative damage to mitochondria leads to a loss of energy resources within the cell. This in turn increases the probability of the cells dying under stressful conditions. Observations have confirmed that mutation rates occur at a much higher frequency in mtDNA than in nuclear DNA. There is also evidence that, with increasing age, genetic damage increases, and there is a decline in mitochondrial activity in nondividing cells, such as heart and kidney cells.³

Mitochondrial scientists Linnane and Ozawa have suggested that clinical interventions may be able to counteract the oxidative damage done to the mitochondrial DNA.⁴ Among the nutrients that can help comprise a mitochondrial protection program are acetyl L-carnitine, coenzyme Q10, DHEA, and alpha-lipoic acid. MCT oil (medium chain triglycerides) also deserves inclusion in such a program.

SUPPLEMENTS CAN HELP PROTECT YOU
FROM OXIDATIVE INJURY AND DNA DAMAGE
Biological systems have evolved a multiplicity of defenses against oxidative attack. To protect the body from free radical and oxidative damage, our cells utilize free radical scavengers - a mixed bag of vitamins, minerals, enzymes, flavonoids, and other compounds that function as antioxidants to neutralize free radicals and other oxidants. A number of important free radical scavengers occur naturally in the body, and many can be found in fruits and vegetables.

While many antioxidants can be obtained from food sources, it is often difficult to get enough from these sources to obtain optimal protection from the constant formation of free radicals. We can minimize free radical damage by taking antioxidant supplements. Researchers have identified a whole arsenal of nutritional antioxidants. These include beta-carotene, C and E, alpha-lipoic acid, and the mineral selenium. Melatonin, the hormone that many people use as a supplement to help them sleep at night, and the components of certain herbs, such as green tea and Ginkgo biloba, also have been shown to have these properties as well.

Many studies have demonstrated the protective benefits that result from taking antioxidant supplements. There is evidence that suggests a protective effect from antioxidant vitamins for ischemic heart disease, cataracts, and some cancers.⁵

However, not all researchers agree that free radicals and other oxidants are the primary cause of aging. When I spoke with Dr. Dean, he told me that "The free radical theory is important, and the consumption of a broad range of antioxidants is certainly beneficial. However, in clinical [animal] studies in which antioxidants have been used, no increase in maximum lifespan has been achieved. I believe that the real key is to consider the hypothalamic theory, and to use various nutrients (and in some cases pharmaceutical drugs) that will restore hypothalamic sensitivity."

BUILT-IN BREAKDOWN THEORIES
The following theories center around the notion that aging is a direct consequence of our genetic programming: the reason we get old and gray is automatically built into our DNA.

HYPOTHALAMIC THEORY OF AGING
The hypothalamic theory of aging holds that the major degenerative diseases are caused by the failure of developmental programs that facilitate the changes between growth stages. These programs, such as hormonally orchestrated changes, are called upon in the "normal" course of aging. Although diseases caused by the failure to accommodate developmental changes are not genetically programmed, they occur in a predictable pattern.

Developmental programs govern our ability, as we age, to adjust and balance when moving from one stage of growth and development to the next. One such succession of programs would be the sexual changes that occur from puberty through to maturity (from menarche through to menopause in women). These programs fail, not in their developmental tasks, but by interfering with the body's ability to return to homeostasis. Homeostasis is the process whereby we control many regulatory mechanisms of our bodies - body temperature, blood sugar levels, cholesterol levels - allowing them to remain within certain limits. Homeostasis enables the body to respond to both internal and external stresses, and yet maintain all of these various physiological and biochemical parameters within tolerable ranges.

An example of the conflict between developmental and homeostasis mechanisms involves the hormone testosterone. In a young child, the production of a small amount of testosterone does not invoke homeostasis and prevent the emergence of puberty. If testosterone's stimulatory powers were adequate to suppress hormones that cause production of the amount of testosterone needed to ensure puberty, then testosterone levels would never rise. The same would be true for the effects of the female sex hormones, estrogen and progesterone. In the developmental "jump" from one early stage to the next, homeostasis is more readily achieved. Later in life, the jump is not so smooth and hormonal homeostasis is never completely reachieved. The imbalance that results then leads to prostate problems and - something from which men may not currently be able to escape - prostate cancer.

Viewed in terms of the brain's regulator of these mechanisms, the hypothalamus, the answer is to help restore the loss of sensitivity that results from failure to reestablish homeostasis. A fundamental approach to retarding the aging process and reversing many age-related diseases would use resensitizers that act to restore the brain's regulatory (hypothalamic) sensitivity. These include the phospholipid phosphatidylserine, the trace mineral vanadyl sulfate, among other substances. Also able to help restore hypothalamic sensitivity is the antidiabetic drug biguanide Metformin^® (a glucophage) that increases insulin sensitivity.

DISPOSABLE SOMA THEORY OF AGING
All body cells are somatic cells except for gametes (sex cells). Somatic cells require fewer resources for maintenance than more precious molecular structures such as those that comprise the DNA of gametes. Evolution has given maximum protection to gametes so that the organism remains in sound condition long enough to pass its genetic material onto future generations. After the ability to procreate ends, there is simply no biological reason to keep the body around. From the perspective of evolution, it's not how long the individual organism survives that counts; it's about preserving the gene pool.⁸ Hence, after reaching sexual maturity, we age and die. Our prehistoric ancestors probably didn't live much beyond 20, on average. The disposable soma theory is static in that it does not readily suggest any solutions to aging but instead represents traditional acceptance to the inevitability of death.

IMMUNOLOGICAL THEORY OF AGING
The immune system appears to be involved in many age-related diseases, many of which are responsive to therapies involving improvement in the immune functions, especially in the elderly. Many studies have shown the immune system peaks at puberty and then gradually declines with age. As the quality and quantity of immune T cells starts to drop, so does the ability to respond to disease. Evidence points to the thymus, which shrinks with age, as key to understanding immune aging.⁹ It's decline is generally associated with an increase in susceptibility to infections and a greater incidence of autoimmune diseases in the elderly.

Because of this, certain antibodies become less effective as one ages, and fewer new diseases can be combated effectively by the body. This causes cellular stress and eventual death. An immune-enhancement program would include various nutrients such as the amino acid arginine, choline, and Vitamin B5, DHEA, progesterone, thyroid, and others.

GENETIC THEORY OF AGING 
When experiments had been conducted on the number of times that a human cell can divide outside of the body, the limit appears to be less than 100 times. This suggests that cell division is genetically programmed, and indeed as the body ages, cell division is limited even more. It is thought that when cell division ends, so does life.

TELOMERE THEORY OF AGING
Every time a healthy cell divides, the ends of its chromosomes grow shorter. These chromosomal endcaps, called telomeres, protect the genetic material and put a limit on the number of times a somatic cell can divide. Recently, it has been shown that shorter telomeres are capable of significantly fewer doublings than those with longer telomeres. Thus telomere length may be a biomarker of cell aging and when telomeres get too short, cell replication slows, and then ends. The organism dies.

An enzyme called telomerase, has been found to protect telomeres from the shortening process caused by repeated cell divisions. It is thought that the reason that telomeres grow shorter with somatic cell divisions is to reduce the risk of cancer, runaway, out-of-control cells that keep multiplying without limit which can be a great danger to the body. Many researchers believe, however, that this safety feature built into the way our cells divide is also one of the factors responsible for aging and death.¹⁰

CHOOSING PROTECTIVE STRATEGIES
While there are diehard adherents for each of the theories of aging summarized in this article, I think that most researchers would agree that many factors contribute to the aging process. This is why it makes good holistic sense to choose a variety of longevity strategies, including an immune enhancement program, an antioxidant regimen, mitochondrial protection supplements, and more. If you're covered on as many fronts as possible, you stand a better chance of being around as more longevity breakthroughs come along.

References

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