Molecular medicine-Other Work Indicating the Central Role of DNA Damage and DNA Repair in Aging

Numerous studies have been performed
in mammals on the correlation between
the ability of cells to repair DNA and
the life span of the species from which
the cells were taken. The life spans of
the species varied from 1.5 years for the
shrew to 95 years for man. Almost all of
the studies showed a positive correlation
betweenDNArepair capacity and life span.
Many experiments have been performed
on the effect of adding antioxidants to the
diets of organisms upon the organism’s
life span. Although the results of such
experiments are not entirely consistent,
certain antioxidants have been found to
generally increase life span. Vitamin E,
for example, has been found to increase
the life span of rat, insects, rotifers,
nematodes, and paramecium.
More than 50 studies have been performed
to examine the possible experimental
acceleration of aging by externally
applied DNA-damaging agents. Overall,
it has been found that sublethal doses
of ionizing radiation or DNA-damaging
chemicals in the diet shorten life span,
but many specific aspects of normal aging
are not accelerated. Several authors
have noted that the distribution (over time
and in different tissues) of DNA damages
induced by external agents does not
closely mimic that of natural damages.
This difference could explain why the
life-shortening effects induced by external
agents do not closely conform to natural
aging. In particular, natural damages probably
accumulate gradually, so they would
tend to build up in nondividing cells, while
they would be diluted out in dividing cells.
Exposure to an external agent over a brief
period, on the other hand, could cause
equally large numbers of damages to nondividing
and rapidly dividing cells. The
effect on rapidly dividing cells could be
very large by interfering with DNA replication.
In addition, if oxidative damages
are important in normal aging, then brain
cells, which have a high level of oxidative
metabolism should have more damages
than most other cell types. Externally applied
damages would not be expected to
produce this particular type of bias. Thus,
the general finding that sublethal exposure
to DNA-damaging agents shortens
life span, while not uniformly accelerating
the natural aging process, is consistent
with the DNA damage theory of aging.