Other Free Encyclopedias » Medicine Encyclopedia » Aging Healthy - Part 4 » Theories of Biological Aging - Random Damage Theories, Programmed Aging Theories, System/organ Failure, Are There Genes For Aging?

Theories of Biological Aging - Random Damage Theories

age theory free oxidative age

The most prominent random damage theoryof aging was proposed by Denham Harman in 1955. This theory postulates that free radical reactions, primarily oxygen-free radicals, cause slowly accumulating damage to nucleic acids, proteins, and lipids that eventually leads to loss of their specific functions in the cell. This damage is caused primarily by the production of oxygen-free radicals as a by-product of normal metabolism in the mitochondria.

Thus, while this damage may be slow, it is continuous, and the well-accepted assumption is that the individual cells are unable to neutralize all of the free radicals generated by the mitochondria or to completely repair the damage that occurs. A small amount of free radicals may also be generated in nonmitochondrial biochemical reactions, and by external insults such as radiation. This general phenomenon is also referred to as oxidative stress, and the theory predicts either that the generation of free radicals increases with age, or that antioxidant defense systems decrease with age, or both.

Many scientific reports have attempted to prove this theory of aging. They document increased levels of oxidative damage with increasing age in a variety of animal model systems, but rarely has it been possible to implicate this increased damage as a cause of aging. Nevertheless, there is strong evidence that oxidative stress is a major factor in the damage occurring following a stroke or heart attack, two major age-related events leading to loss of organ function or death. It is also thought that oxidative stress is a factor in the age-related loss of neurons that accompanies a variety of neurodegenerative pathologies. Thus, any comprehensive theory of aging must include oxidative stress as a likely factor in the loss of biological function through human aging.

The free radical, or oxidative stress, theory of aging is a prototype for other, similar theories that suggest random damage occurs and that much, but not all, of it can be repaired. Complete repair is thought to be impossible, so damage slowly accumulates and eventually leads to dysfunction and overt pathology. These related theories include error catastrophe theory and DNA damage theory. The glycation theory of aging proposes that the nonenzymatic condensation of glucose with amino groups in proteins leads to dysfunction of those proteins, a process that is accelerated in diabetics because of their increased level of circulating glucose. This is well documented in hemoglobin, and for proteins in the eye lens, leading to premature cataract formation. Glycation also leads to protein cross-linking, which not only alters both the structure and function of these proteins, but also prevents their normal degradation. The rate of living theory proposes that aging rate is proportional to the rate of the organism’s metabolism, so that small mammals with high metabolic rates, like mice, will have much shorter life spans than large mammals, such as humans. This may generally be true for mammalian species, but birds live much longer than might be predicted by their high metabolic rates and high circulating glucose levels. The wear and tear theory of aging is a similar version of this class of theories.

Theories of Biological Aging - Programmed Aging Theories [next]

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