Life
is a Devil's Bargain: Cancer or Aging
By
Ker
Than
LiveScience Staff Writer
Deterioration
of body and mind are the prices our bodies pay for
protection against
cancer
as we grow older, new studies suggest.
Scientists have discovered that a gene
involved in tumor suppression also plays an important
role in determining when certain cells in the body
cease multiplying and
start
deteriorating. As cells age, the gene,
called p16INK4a, becomes more active. The cells
have greater protection against cancer but lose
the ability to divide. Cells that don't divide die
off and are not replaced.
The studies, detailed together in the Sept. 7 issue
of the journal Nature, suggest the physical and
mental
ravages that accompany aging
are not the result of simple wear and tear of the
body, but of a cellular decline that is programmed
into our genes-one designed to safeguard us against
copying mistakes that become more frequent as we
grow older.
"This research tells us why our old tissues
have less regenerative capacity than young tissues,"
said Sean Morrison of the University of Michigan,
who was involved in one of the studies. "It's
not that old tissues wear out-they're actively shutting
themselves down, probably to avoid turning into
cancer cells."
No free lunch
Research teams from three medical schools examined
the role of p16INK4a in cells collected from different
parts of the body in mice.
One team, from the University of North Carolina
(UNC) at Chapel Hill, looked at the gene's role
in pancreatic islet cells, which produce and secrete
the hormone insulin
and which are defective in persons with Type 1 diabetes.
Another team from the University of Michigan examined
brain stem cells while a third, from
Harvard University, looked at p16INK4a in blood
stem cells.
All three studies found similar results: as animals
got older, p16INK4a activity increased and the cells
eventually stopped dividing. Cells in mice deficient
in the gene continued to divide but were more likely
to turn cancerous, while cells in animals with over-expression
of the gene stopped dividing earlier and aged prematurely.
The experiments also showed that cells taken from
old animals remember their "age" and continue
to deteriorate at their previous rate even when
transplanted into young animals.
This last finding raises new questions about the
usefulness of adult
stem cells in tissue and organ repair
compared to embryonic
stem cells.
Fresh debate
The use of embryonic stem cells in medical
research is currently a topic of
fierce
debate because harvesting the cells destroys
developing embryos. As an alternative,
some scientists are trying to use stem cells taken
from adults and grow them into tissues in the lab;
the new cells could then be reintroduced into the
patient's body to replace failing tissues or organs.
"I think this data undermines that notion,"
said Norman Sharpless, a researcher at the University
of North Carolina (UNC) at Chapel Hill who was involved
in all three studies. "It shows that even these
[adult] stem cells, which have the properties of
self-renewal, are not limitless in their capacity
to regenerate themselves. There are tumor-suppression
mechanisms that limit their longevity."
Not all of the researchers agree. Morrison, the
University of Michigan researcher, doesn't think
the findings will have a drastic impact on how doctors
use stem cells.
"I don't think this is a reason to say that
embryonic stem cells are more valuable that adult
stem cells," he said in a telephone interview.
"It's been recognized for a long time that
young adult [stem] cells are more robust than old
ones. For example doctors are reluctant to do bone
marrow transplants when the donor is old."
The more important consequence of the new findings,
Morrison said, is that it helps explain embryonic
stem cells seemingly limitless ability
to divide and become new cells.
These tumor-suppression "mechanisms probably
don't exist in embryonic stem cells, and that's
why they can proliferate indefinitely, while adult
stem cells can't," he said.
Potential uses
The findings could prove to have numerous practical
uses as well, the researchers say. For example,
p16INK4a could be used as a "biomarker'
to determine a cell's age. It is "like an odometer
almost-you can use it to tell the mileage of the
tissue," Sharpless told LiveScience.
This could allow doctors to one day do things like
sort blood stem cells based on physiological age
to determine whether someone will be a good bone
marrow donor or not.
Also, it might be possible to create drugs that
temporarily inactivate p16INK4a and promote healing
in damaged cells, Morrison said.
"We could give people who have injuries a drug
like that for a week or two weeks or a month,"
he said. "That's not likely to cause cancer,
and even if some cells started to divide a little
out of control during that period, you just stop
the drug and p16INK4a comes back on and shuts things
down again."
The findings might also lead to new kinds of therapies
aimed at slowing
or reversing the effects of aging, the
researchers say. In the experiments, shutting down
p16INK4a activity relieved only some, but not all,
of the negative repercussions of aging. But scientists
know of other tumor suppressor genes, and manipulating
many of them at once might have a greater effect,
Morrison said.
"Maybe if we look at the aggregate effects
of five or six different tumor suppressors, we might
be able to rescue most
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