Theories Of Aging

There are more theories of aging than facts. Aging clearly occurs at different rates for different species, and even within a species, aging occurs at different rates among different individuals. The only reasonable conclusion is that aging must be genetically controlled, at least to some extent. Both within and between species, lifestyle and exposures may alter the aging process.

Most gerontologists view senescence as a collection of degenerative entropic processes related only by the fact that they occur over time. Some theories of aging address what controls these processes and why the controls exist as they do. Other theories of aging address the issues of whether senescence is more programmed than random entropy, thus offering some advantage for a species. For example, senescence may have evolved because without it, a species would accumulate ill-adapted older members. These members would compete with potentially better adapted younger members, slowing the rate at which adaptive mutations are introduced.

Loose cannon theory: This theory posits that an entropy-producing agent--free radicals or glucose--slowly disrupts cellular macromolecular constituents. Theoretically, free radicals, generated during oxidative phosphorylation, can variously modify macromolecules, primarily through oxidation. Considerable evidence suggests that oxidative damage increases with age. For example, in older organisms, specific amino acids in specific proteins tend to be oxidized residues, leading to decreases in the specific activity of these proteins. Additionally, specific oxidized derivatives of nucleotides from DNA increase in frequency. Experimentally induced simultaneous overexpression of superoxide dismutase and catalase (enzymes that attenuate free-radical damage) increases the life span of fruit flies by about 30%.

Glucose is thought to promote senescence mainly through nonenzymatic attachment to proteins and nucleic acids, through the same process that produces glycated hemoglobin. Glycated protein levels increase with age. Otherwise, there is little direct evidence that glycation has a major role in senescence. However, because dietary restriction increases maximum life span and also reduces blood glucose and the rate of glycation, interest in glycation's role in senescence continues.

Rate of living theory: This theory posits that smaller mammals tend to have high metabolic rates and thus tend to die at an earlier age than larger mammals. Thus, this theory is related to the idea that free radicals and other metabolic by-products play a role in senescence. However, studies of metabolic rates have shown wide variation in the correlation between size and longevity, undermining the credibility of this theory.

Weak link theory: This theory posits that a specific physiologic system--usually the neuroendocrine or immune system--is particularly vulnerable (presumably to entropic processes) during senescence. Failure of the weak system accelerates dysfunction of the whole organism. Failure of the neuroendocrine system would be expected to produce profound impairments in homeostatic systems, including loss of reproductive function and metabolic regulation, which occur with age. Failure of the immune system would be expected to produce an increased susceptibility to infection and a decreased ability to reject tumor cells. However, there is little evidence that failure of either system directly contributes to age-related diseases or to mortality (in contrast, for example, to the direct contribution of a compromised immune system to mortality in patients with AIDS). Furthermore, even if this theory explains some manifestations of aging in higher organisms, it does not explain aging in lower organisms, and little is known about the primary mechanism behind such weakness.

Error catastrophe theory: This theory posits that errors in DNA transcription or RNA translation eventually lead to genetic errors that promote senescence. Although data suggest that older organisms have altered proteins reflective of such genetic changes, this theory does little to explain most observed age-related changes.

Master clock theory: This theory is one of the oldest theories of aging and no longer has high credibility; it states that aging is under direct genetic control. Teleologically, it suggests that the rate of aging within each species has developed for the good of each species. Individual variation develops because of maladaption, exposure, and lifestyle. In the wild, such maladapted individuals tend to die out and the well-adapted ones persist, altering longevity in the best interest of the species.

Exactly what controls the rate of aging is unknown. It could be a gene that controls telomere shortening or some other process of cell division. Or it could be genetic control of another cellular process not involved in division, such as DNA repair, thus resulting in apoptosis.