Abstract
Aging is the accumulation of changes that increase the risk of death. The major contributors after age 28 years are the endogenous chemical reactions that, collectively, produce aging changes that exponentially increase the chances for disease and death with age. These reactions constitute the "inborn aging process." This process is the major risk factor for disease and death of the 98% to 99% of cohorts still alive at age 28 in developed countries, where living conditions are now near optimum.
The Free Radical Theory of Aging (FRTA) and, simultaneously, the discovery of the ubiquitous, important involvement of endogenous free radical reactions in the metabolism of biologic systems, arose in 1954 from a consideration of aging phenomena from the premise that a single common process, modifiable by genetic and environmental factors, was responsible for the aging and death of all living things. The FRTA postulates that the single common process is the initiation of free radical reactions. These reactions, however initiated, could be responsible for the progressive deterioration of biologic systems with time because of their inherent ability to produce random change. The theory was extended in 1972 with the suggestion that the life span was largely determined by the rate of free radical damage to the mitochondria.
The FRTA suggests the possibility that measures to decrease the rate of initiation and/or the chain length of free radical reactions may, at least in some cases, decrease the rate of reactions that produce aging changes without significantly depressing those involved in maintenance and function. Many studies support this possibility.
Applications of the FRTA have been fruitful. For example, it is a useful guide to efforts to increase the life span, and it provides plausible explanations for the aging phenomenon (e.g., the association of disease with age as well as insight into pathogenesis; the gender gap; the association between events in early life and late onset disease; and the shortening of telomeres with cell division). Further, it is reasonable to expect on the basis of animal and epidemiologic studies that the increasing population-wide use of antioxidant supplements and ingestion of foods high in antioxidant capacity over the past 40 years have helped to increase the functional life span of the population by contributing significantly to the decline in "free radical" diseases, to increases in the fraction of elderly, and to the decline in chronic disability in this group.
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