Re : AGING/A4M update

Joao Pedro de Magalhaes (
Wed, 15 Dec 1999 15:46:02 +0100


>On Tue, 14 Dec 1999, Joao Pedro de Magalhaes wrote:
>> I didn't know you were such a big fan of the telomerase theory!
>Only in cells with a moderately high division rate, i.e. epithelial
>(skin, lung, gut) cells, endothelial cells at high arterial stress
>locations and perhaps T-cells (that might wear out with HIV

That does not explain aging in postmitotic animals like Drosophila and C.elegans. Perhaps they age for a different reason than we do; which is something I'm becoming more convinced every day.

>> Also, don't you think
>> research based on Hayflick's limit (as most telomerase research is) can be
>> biased? How do you explain that cells taken from species that appear not to
>> age also follow Hayflick's limit and also have a latent period in
>> accordance with donor age.
>The question revolves around whether or not a cell *must* divide to
>not age. I could make the case that in mammalian species, there is
>an accumulation of metabolic byproducts (over very long time scales)
>that the cells do not know how to get rid of. The only way to
>prevent these from destroying cell functioning is to divide to dilute
>them down to a managable level. Now, a "non-aging species" may have
>mastered what is known to computer scientists as "garbage collection".
>In that case they would have no need to divide except to grow.
>Unless you have a clever genetic program to "grow" and "ungrow"
>very cleanly, growing indefinately might not be a good idea.
>At some point you exhaust the food resources, then cells start
>dying, then bacteria will come along to feed on the decayed material
>and they might start attacking the living material as well, etc.
>So a non-aging species might have a "Hayflick limit" because
>exceeding your food resources makes you an invitation to creatures
>that might threaten your life.

Many non-aging species do appear to grow indefinately (lobsters, certain turtles, etc.). In fact, Bidder's hypothesis was that species with unlimited growth would not age (constant expansion or death, a bit transhuman once you think about it). Although there are exceptions to this rule, the truth is that non-aging species' cells do undergo mitosis (one good exaple is the molting in lobsters). My personal opinion is that, although telomeres are likely to have some relation to aging, the telomerase theory, despite elegant, is not the complete picture.

>> In addition, there is evidence indicating that
>> telomerase is not the only enzyme controlling telomere lenght.
>I'm unaware of this, but this might certainly be true. If the telomere
>length controlling mechanism is very old and the mammalian genome
>has been duplicated twice then there might be at least 4 paths
>controlling telomere length.

I'm presently organizing my bibliography (so I'm not sure these are the best articles) but this is what I could find, should you want to know more:

Bryan T. M., Englezou A., Gupta J., Bacchetti S. and Reddel R. R. (1995). ³Telomere elongation in immortal human cells without detectable telomerase activity.²
Embo J 14(17): 4240-8.

Zhu L., Hathcock K. S., Hande P., Lansdorp P. M., Seldin M. F. and Hodes R. J. (1998).
³Telomere length regulation in mice is linked to a novel chromosome locus.² Proc Natl Acad Sci U S A 95(15): 8648-53.

Best wishes.

Joao Pedro de Magalhaes

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