By far, one of the most popular theories of aging is the “Free Radical Theory of Aging.” This theory was first proposed by Dr. Denham Harman (1) and postulates that aging results from an accumulation of changes caused by reactions in the body initiated by highly reactive molecules known as “free radicals.” The changes induced by free radicals are believed to be a major cause of aging, disease development or death. A major premise in this theory is that free radicals and their precursors may be produced endogenously (within the body) through normal metabolic processes, or exogenously (outside the body) from sources such as cigarette smoking.
The body’s defense mechanisms against these free radicals are referred to as antioxidants. When the amount of antioxidants in the body is insufficient to do battle with the free radicals, these very reactive molecules easily react with vital molecules in the body, such as DNA, causing mutations (alterations) in the sequence of genetic material. The accumulation of changes is then thought to lead to the development of aging and degenerative diseases.
There are a number of reasons why the free radical theory has remained popular and withstood the test of time (2). First, it provides many plausible explanations for the process of aging. Second, there are a growing number of studies that implicate free radical reactions in the development of many chronic, age-related diseases. Third, the free radical theory of aging can easily be tested indirectly, using dietary experiments with antioxidant supplements. Fourth, the free radical theory is the only one that encompasses all the concepts in almost all the other theories of aging (except the neuroendocrine theory).
For instance, the free radical theory integrates all the theories that pertain to metabolism and energy expenditure with the theories dealing with molecular changes (mutations) at the DNA level. Thus, it is easy to see how increasing the metabolic rate would generate an explosion of free radicals or reactive oxygen species (ROS). The reactive oxygen species would, in turn, react with DNA to cause mutations, which could lead to the development of disease—especially cancer.
Sources of Free Radicals
As stated previously, free radicals (oxidants) come from two major sources: (a) endogenous and (b) exogenous. Endogenous free radicals are produced in the body by four different mechanisms. First, from the normal metabolism of oxygen-requiring nutrients, Mitochondria —the intracellular powerhouses which produce the universal energy molecule, adenosine triphosphate (ATP)—normally consume oxygen in this process and convert it to water. However, unwanted by-products—such as the superoxide anion, hydrogen peroxide and the hydroxyl radical—are inevitably produced, due to incomplete reduction of the oxygen molecule. It has been estimated that each cell produces more than 20 billion molecules of oxidants per day during normal metabolism. Imagine what happens with inefficient cell metabolism!
Second, white blood cells destroy parasites, bacteria and viruses by using oxidants such as nitric oxide, superoxide and hydrogen peroxide. Consequently, chronic infections result in prolonged phagocytic activity and increased exposure of body tissues to the oxidants.
Third, other cellular components called peroxisomes produce hydrogen peroxide as a byproduct of the degradation of fatty acids and other molecules. In contrast to the mitochondria, which oxidize fatty acids to produce ATP and water, peroxisomes oxidize fatty acids to produce heat and hydrogen peroxide. The peroxide is then degraded by an enzymatic antioxidant called catalase. Under certain conditions, some of the hydrogen peroxide escapes to wreak havoc into other compartments in the cell.1
Finally, an enzyme in the cells called cytochrome P450 is one of the body’s primary defenses against toxic chemicals ingested with food. However, the induction of these enzymes to prevent damage by toxic foreign chemicals like drugs and pesticides also results in the production of oxidant by-products.
Exogenous sources of free radicals include air pollution, of which industrial waste and cigarette smoke are major contributors. Cigarette smoke literally bristles with oxidants. Radiation and trace metals, notably lead, mercury, iron and copper, are also major sources of free radical generation. Normal diets containing plant foods with large quantities of certain compounds such as phenols and even caffeine may contribute to the exogenous supply of oxidants to the body.
The combination of oxidative damage by exogenously and endogenously produced free radicals has ominous consequences for body tissues. The oxidants induce alterations in the structures of tissues and in their functions, which manifest as aging and chronic degenerative diseases like arthritis, atherosclerosis, and cancer.
Fortunately, one approach to preventing free radical damage to cells is through the liberal supplementation of antioxidant nutrients like vitamins A, C and E, minerals like selenium, and nutritional antioxidant cofactors like lipoic acid. Another approach is to use chelating substances like chlorella and EDTA to remove free-radical promoting toxic heavy metals.
- 1. Harman D. Aging: A theory based on free radical and radiation chemistry. Univ. Calif. Rad. Lab. Report No. 3078, July 14, 1955.
- 2. Harman D. Free radical theory of aging. In: Free Radicals and Aging, Emerit I and Chance B (eds.), Birkhauser Ver
|
