Premature Ageing

Guy Dunphy GuyD at world.net
Sat Mar 30 10:09:44 EST 1996


Oliver Bogler <obogler at ucsd.edu> wrote:

>Guy Dunphy wrote:

>> Anyone know if more recent work has examined the condition of the telomeres
>> in Werner syndrome patients?

Well?

>> Isn't it amazing the number of researchers who are looking into telomeres,
>> 'just for the cancer connection'!
>> What a bunch of funding whimps. Go on, admit it you guys, WE ALL WANT TO BE
>> IMMORTAL.

>> Another thought: Given the prime ageing mechanism may be so simple, just a 'bit
>> of string' that gets shortened till its all gone, 

>> Interesting thought. Can anyone think of any fossil record data that would
>> allow estimation of real 'age at death' of early human fossils? Not just age
>> estimated by comparison of structure to modern humans. Bones don't have age
>> rings like trees, do they? And carbon dating gives time from then till now,
>> not 'lifetime' age.

>This is all very interesting, but you seem to unaware that there is no evidence of a 
>connection between telomere length/cellular ageing and organismal ageing. Organismal 
>ageing is better discussed in terms of mortality - no one dies of "old age". 

Oddly enough, that was what my grandfather died of.

>There is always a "pathology", and that has nothing to do with telomere length.

Now who' s making unproven assertions?  

>Of course, older 
>people have older cells that may be less good at doing their stuff, contributing to a 
>conditions that kills.

Exactly. Even  where infectious disease was the cause of death, perhaps an
immune system with a smaller proportion of 'tellomere challenged' cells would
have mounted an effective defense. So how do we ever decide whether the root
cause of a particular death was short tellomeres. Can't. All we can do is see if
an experimental population with 'new, improved' tellomere restoration has longer
average lifetimes than a control.

>Would you really argue that telomere lenght killed George Burns and 
>Sergei Gringkov?

Sorry, I can't remember what George Burns died of (other than being very old).
But probably yes. Who was Sergei Gringkov?

>Also, the fossil record would look at people with no basic health care or sanitation, that 
>were predated actively. Hardly a fair comparison. 

My point was, that all other things (predation, lifestyle, etc) remaining equal,
there may have been a relatively sudden change in average human lifespan.
I wondered if any one could examine a human bone fossil and say: "Hey, this
fellow was 200 years old when he died!"  How would we tell?
Are there no instances of other species, where there are two distinct strains,
differing only in their average lifespans? Which strain would win out in an
evolutionary contest?

>In general, in the wild, animals never 
>reach their maximum possible age because they get eaten first!

Probably true, animals always get eaten before 'maximum' age. But humans
(even prehistoric ones) have social structures that tend to distort such purely
ecological models.

>So I guess, most scientists who work on telomeres do so to learn more about tumors, than 
>for the sake of living forever. Also the connection between cellular ageing and telomere 
>length is so far only correlative: no direct evidence of causation has been provided.

And the way to prove it, is to switch on the teleomere patch-up system in a cell
line, and see what happens. You know that, right? Anyone trying to do it?

Then of course, if a multicellular organism was 'tellomere patched' it would
have the problem that every cell that went feral would result in a full-on
cancer, rather than just a bunch of cells that multipled out of control for 40
or so generations then died off.
Problems, problems...  But its a start.

Certainly, I'm aware there is no direct proven link yet. But then, I'm not
writing research papers, I'm just speculating. So I don't have to stick to
discussion of proven facts.  Nor am I engaged in the field, and so constrained
to be careful of what I say for reasons of professional standing. I'm just a
computer programmer who reads NewScientist & Sci-Amer. with interest,
particularly noting the parallels between computer science and genetics.

And in this case, my speculation is that as the telomeres shorten (at differing
rates) in the various populations of cells in the body,  and the statistical
spread (of cells in each line that have exhausted their telomeres and begun to
suffer loss of whatever genes were nearest the fraying ends) alters, then that
seems likely to me to result in the wide range of effects that are involved in
aging.

After all, there are _lots_ of variables. Telomere exhaustion will doubtless
occur at different rates in different:-
   - individuals  (hence the spread of rates of aging between people)
   - cell lines (so different organs and metabolic systems will 'age' 
     differently in any individual)
   - individual chromosomes (and hence 'hit' different genes first - so the  
     mechanisms of failure will be many and varied.)
In a given individual, with so many different modes of failure coming into play,
all of them in statistical fashion among cell populations (rather than all or
nothing effects), then its no wonder that aging looks like a general systemic
decline in effectiveness.

Then again, I'd be surprised if other age related problems (such as mechanical
and structural wear and alteration) don't show up in the first experimental
subjects to have their 'telomere aging' fixed. 
For instance, there's also the mitochondria functionality problem.

But I just have a gut feeling that telomere loss is the major cause of the
'cellular death' clock.  (Hope its not just wishful thinking.)


Incidentally, while I'm talking to someone who no doubt knows, are there
any listservers that carry more detailed information about this topic?
I'd very much like to subscribe to them. Your advice would be greatly
appreciated.  If you do, could you please email to me, my server here
in Sydney seems to miss a lot of US posts.

Regards,
GuyD             guyd at world.net              Sydney, Australia.





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