Between Scylla and Charbydis: Aging and Cancer. |
Created January 15th, 2002. Copyright 2002 by Duane Hewitt
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A recent report has connected the phenomena of aging and cancer
relating them as opposing perils that we must evade. By escaping one of them
we must be careful that we do not march into the maw of the other. I have
previously alluded to the connection between aging and cancer. The recent
data from mice with a mutated version of the p53 gene have provided
further experimental support for this connection.
The p53 gene has long been to known to act as a sentry against
cancer. It performs this function by detecting DNA damage within cells and
instructing the damaged cell to commit suicide. In a majority of cancers p53
is inactivated which allows the cell to progress down the path to becoming
cancerous. To study this process many mice have been produced with mutations
in p53 that increase susceptibility to cancer. In fact mice that have the p53
gene deleted live only forty to forty-five weeks compared to normal mice which
can live up to 164 weeks maximum. This is due to a large number of serious tumors
forming in these mice and causing them to have early mortality.
Several years ago some mice were made in which p53 function was
enhanced rather than reduced. This was an unintended outcome and initially they
were left to grow and breed to maintain the line. At one point it was noticed
that even though these mice had a substantially reduced incidence of cancer
they had a reduced lifespan when compared to mice with normal p53. This was
surprising because you would expect that eliminating cancer, which is considered
a disease of aging, would extend the healthy lifespan of animals. However these
mice had an average lifespan of 96 weeks compared to 118 weeks for normal mice.
These mutant mice not only die earlier but they display many of
the symptoms of aging earlier than normal littermates. Extensive studies were
undertaken that compared these mice with normal mice at the same age. Accelerated
aging was observed in eighteen month old mice. The signs of aging observed were
weight loss/muscle mass reduction, losses of organ tissue mass, osteoporosis,
changes in blood composition, changes in bone thickness, reduced wound healing
and reduced hair regrowth. Some signs of aging that were not observed were liver
diseases, graying of hair, brain atrophy, joint diseases or cataracts.
From these results it appears that p53 cancer inhibiting activity
can be hazardous to our health if taken to an extreme. It may be that mutant p53
has a lower tolerance for damage to cells and therefore shuts down growth and
triggers cell suicide at a lower threshold than normal p53. It is thought that the
growth inhibition may be occurring at the level of the stem cells.
So from these mice it appears that we may need to walk a tightrope
between cancer and aging if we seek any meaningful extension of the human life
span. We must be careful about applying data from mice directly to humans because
several important differences exist in aging mechanisms between us and them. One
example is that human telomeres appear to play a role in aging while telomeres do
not appear to play a role in aging in mice. Telomeres also play a role in human
cancer but not in cancer in mice. Therefore these results while quite illuminating
will not be the final word in either the cancer story or the aging story.