The Free Radical Theory Overview

"The perpetual but futile struggle of individual cells to stay alive and function normally, in the face of chemical disintegration - is the genesis of aging and all its consequences...Indeed, the free radical theory of aging is so big it encompasses virtually every disease you can think of that comes with increasing age. That, then, makes aging the primary and only disease most of us ever have to worry about. As Dr. Harman notes, we have pressed the life span about as far as it will go without attacking aging at its origin... Degenerative diseases such as cancer, Lou Gehrig's disease and Alzheimer's are not separate and distinguishable entities. They are merely different forms of expression, influenced by genetics and environment, of the free radical aging process that has caught up with us. "

- Jean Carper (excerpted from Stop Aging Now!, published in 1995 by HarperCollins)


The free radical theory of aging is that organisms age because cells accumulate free radical damage with the passage of time. In general, a "free radical" is any molecule that has a single unpaired electron in an outer shell. For most biological structures, free radical damage is closely associated with oxidation damage. Most people can understand oxidation damage as they are familiar with the process of rust formation. As the name suggests, antioxidants, like vitamin C, prevent oxidation. A nutrient's ORAC Score is a method for determining its total antioxidant capacity and thus its ability to prevent oxidation.

In biochemistry, the free radicals of interest are often referred to as reactive oxygen species (ROS) because the most biologically significant free radicals are oxygen-centered. But not all free radicals are ROS and not all ROS are free radicals. For example, the free radicals superoxide and hydroxyl radical are ROS, but the ROS hydrogen peroxide (H2O2) is not a free radical species, however the term "free radical theory of aging" usually refers to these compounds as well.

The free radical theory of aging was conceived by Denham Harman at a time when most scientists still believed that free radicals were too unstable to exist in biological systems and before anybody had invoked them as a cause of degenerative diseases. Harman drew inspiration from two sources: 1) the rate of living theory, which held that lifespan was an inverse function of metabolic rate, oxygen consumption. 2) Rebbeca Gershman's observation that hyperbaric oxygen toxicity and radiation toxicity could be explained by the same underlying phenomenon: oxygen free radicals. Noting that radiation causes "mutation, cancer and aging" Harman argued that oxygen free radicals produced during normal respiration would cause cumulative damage which would eventually lead to organismal loss of functionality, and ultimately, death. In later years, the free radical theory was expanded to not only include aging per se, but also age related diseases. Free radical damage within cells has been linked to a range of disorders including cancer, arthritis, atherosclerosis, Alzheimer's disease, and diabetes. This involvement is not at all surprising as free radical chemistry is an important aspect of phagocytosis, inflammation, and apoptosis. Cell suicide, or apoptosis, is the body's way of controlling cell death and involves free radicals and redox signalling. Redox factors play an even greater part in other forms of cell death such as necrosis or autoschizis.

More recently, the relationship between disease and free radicals has led to the formulation of a greater generalization about the relationship between aging and free radicals. In its strong form, the hypothesis states that aging per se is a free radical process. The "weak" hypothesis holds that the degenerative diseases associated with aging generally involve free radical processes and that, cumulatively, these make you age. The latter is generally accepted, but the "strong" hypothesis awaits further proof. Both models trace back to Dr. Harman's work.