"Reversing Human Aging" by M. Fossel

Axel Kowald a_kowald at chemie.fu-berlin.de
Mon Jun 10 05:17:24 EST 1996


Reading the posting about Fossel's book I couldn't resist answering.
I'm a biochemist and got my PhD about theoretical studies of the aging process
(mathematical modelling). It is true that one of the most interesting results in
aging research during the last years was the discovery that human telomeres are
shortening with time. However, I believe one should be very (!!) cautious to 
believe that this is the true underlying cause of the aging process. This can be
a very long discussion with pros and cons, so I just want to mention a few points
to think about.

Firstly, as with all other ideas about aging it is very difficult to decide if
the telomere shortening is really the cause or only a consequence of the aging
process. It could also be that telomere shortening has developed independently of
aging as a evolutionary neutral event. What I mean is suppose that aging was
there first and in the very early days all animals were happily expressing
telomerase. Then there was a mutation which stopped the synthesis of telomerase
in somatic cells. It could be that this was of no consequence whatsoever (it was
neutral), because the animals die a long time before somatic telomere shortening 
causes any problems. 

Another point is that neurons don't divide and shouldn't have telomere
shortening, but nevertheless they show age related changes. Why ?

One could say that if the surrounding cells go down hill it could also affect the
nerve cells. But a more drastic example in this respect are for instance insects.
As soon as they are adult they are post-mitotic, which means that they have no
dividing cells !!    But of course you know that flies and also the flatworm
Caenorhabditis elegans (which too is post mitotic) die after a few weeks.
If you take their cells you will see that they show standard signs of aging like
an increase in radical production, drop of protein synthesis or increase in
oxidised proteins. And all that without telomere shortening !!

I said when they are adult they are post-mitotic, but of course they have to
divide from the point of the fertilised egg to the adult stage and during that
time they have to maintain the lengths of their telomeres like all the other
organisms. However, there are strains of Drosophila which are defective in
maintaining their telomere lengths during that critical time. As expected their
telomeres are shortening from generation to generation but the life-span is not
affected !!    The guess is that in the long term (after many generations) these
strains will develop problems and  may finally all die, but in the short term it
doesn't seem to influence life-span.  

But having said all this I too think that it is very very important to express
telomerase in somatic cells and see what happens. This will be the definitive
experiment. And in this respect I agree with Fossel. I would guess the first
transgenic animals which carry an active telomerase gene will be generated within
the next 5-10 years.  But unlike Fossel I wouldn't bet too much on telomere
shortening as cause for the aging process. A telomerase inhibitor might however
be useful as anti-cancer drug and as far as I know this is actually the main
motivation of most people and companies with work on it.

	Axel Kowald

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