Nearly 50 years ago, Dr. Denham Harman proposed the free radical theory of aging, which suggests that aging is caused by highly reactive molecules called free radicals. The theory received less than enthusiastic acceptance from the scientific community. Since that time, however, many scientists throughout the world have studied the complex relationship between free radicals and aging. Their findings have supported Dr. Harman’s original hypothesis. Today, the free radical theory of aging is widely accepted as one of the foremost explanations for the aging process and recognized as a practical guide to a longer, healthier life span.

A free radical is an atom, molecule or molecular fragment that contains at least one unpaired electron (in contrast to normal molecules, which contain only paired electrons). Free radicals, together with non-radicals that contribute to free radical production, are often referred to as reactive oxygen species. Free radicals are a byproduct of aerobic, or oxygen-using, metabolism that generates ATP, the cell’s energy source, from the foods we eat. During this process, which occurs in specialized cell parts called mitochondria, electrons are passed from molecule to molecule. Most of the electrons (97-99%) are taken up by oxygen at the end of the transport chain. The remaining electrons combine incorrectly with oxygen to form superoxide, a free radical that is the major source of other free radicals in the cell.

Having an unpaired electron makes a free radical unstable, so it tries to stabilize itself by either gaining an additional electron or losing its unpaired electron. It can only accomplish this by reacting with other cell molecules, such as proteins, lipids, and DNA. When the free radical gains or loses an electron, it converts the donor/recipient molecule into a free radical, thus initiating a destructive cascade of free radical reactions.

Free radical reactions cause widespread damage to the cell molecules and, subsequently, the cells themselves. Many of the detrimental effects of free radical reactions occur within the mitochondria, particularly the mitochondrial DNA, which contains the genetic information needed for the production of proteins and other molecules used during energy production. Unlike damage to the DNA of the cell nucleus, damage to mitochondrial DNA is not often repaired. Instead, it accumulates, leading to ever-increasing functional impairment. Other molecules also cease to function normally when damaged by free radical reactions. This, in turn, disrupts the vital cellular systems that require those molecules for proper functioning. When the damage inflicted by free radical reactions becomes so severe that the cell cannot repair it or compensate for it, the cell dies. If this process occurs in many cells throughout an organ or tissue, the result can be irreversible organ failure. Research has shown that the damaging effects of free radicals on molecular and cellular function are involved not only in aging, but also in diseases such as atherosclerosis, cancer, and Alzheimer’s disease.

The body is not defenseless against free radical damage. Many free radicals are detoxified by specialized enzymes and molecules called antioxidants. However, if free radical production is increased and/or antioxidant activity is decreased, the incidence of free radical reactions escalates, with potentially disastrous effects. The free radical theory of aging attributes the aging process to an imbalance between free radicals and the body’s defenses against them. The influence of free radicals on disease processes is undoubtedly determined by this relationship as well. Much of the research summarized in this volume addresses the complex actions of free radicals in living systems. There are other theories of aging, however, and they are respresented as well. What is most important and most evident, regardless of the theory embraced, is the common goal shared by all of the researchers: to unravel the mystery of why and how we age.