 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.
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