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Theories of Aging

An Overview of the Theories of Aging
Why Do We Age?
By David Jay Brown
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, includingBiological 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

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.

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.

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.

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 teaand 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

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