Telomeric Theory of Aging

Beverly Erlebacher bae at cs.toronto.edu
Wed Aug 19 12:55:43 EST 1998


In article <35daf0c8.354067837 at nntp.ix.netcom.com>,
 <ufotruth at ix.netcom.com> wrote:
> 
>I have a question. I have heard lately of the creation of telomerase
>"Knock Out Mice" that have the gene for telomerase removed from them.
>Do you think it is possible that mice could be created or genetically
>engineered that had the telomerase gene in every single one of their
>cells? 

Note that the telomerase knock-out mice had normal life spans for *six*
*generations* of steadily decreasing telomere length.  THe only apparent
effect was that the sixth generation was sterile.

Telomeres seem to always be a lot longer than necessary in mammals.  Cats
and mice have telomeres many times longer humans do (about 15 or 20 times).
A study done about 10 years ago on telomere length vs chronological age in
humans showed that even people 120 years old had plenty of telomere left,
though definitely shorter than those of younger people.

>It seems that this would be an awsome experiment if it could be
>performed. It could help us deterimine just how much telomerase
>therapy could increase lifespan, whether activiation of telomerase
>causes cancer, and whether there are any other side effects.

The mice, and the rest of us, already have telomerase gene in every cell,
but it isn't activated in most of them.  Activating telomerase in cultures
of normal cells results in normal cells that seem to be able to continue 
to multiply beyond the Hayflick limit without showing cancerous behaviour.

Most but not all cancers have telomerase activated.  It's possible that 
inactivation of telomerase is an anti-cancer mechanism - once the telomeres
get short, they get 'sticky' and chromosome abnormalities easily occur.
This appears to cause DNA repair mechanisms to 'decide' the cell is a lost
cause, and apoptosis gets activated causing the cell to self-destruct. This
is exactly the right thing to do if the telomeres got shortened because the
cells have been multiplying unboundedly, an early stage or pre-cancerous
condition.  It's possible that this sort of thing happens frequently, and
only cells that manage to activate telomerase or acquire mutations in the
repair or apoptotic mechanism can break past this barrier and become real
malignancies.

If the above is true, my guess is that animals with telomerase activated
in every cell would be prone to more cancers at younger ages than normal
mice.  Apart from the cancers, I wouldn't expect lengthened life spans,
since total absence of telomerase and significantly shortened telomeres
from conception didn't affect the longevity of telomerase knock-out mice.

One potential use for telomerase-activated cell lines would be to help
reconstitute the immune system when it has been destroyed by chemotherapy,
radiation or disease.  Bone marrow transplants haven't been around long
enough to tell us whether recipients will experience a deterioration of
the immune system similar to that experienced by elderly people, but at a
much younger age.  This method might also be used to help enhance the
immune systems of the elderly.  However, it will take quite a lot of work
and time to determine whether such a therapy is, instead, just a way of 
giving the patient leukemia or other serious bone marrow disease in months,
years or decades.




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