Rate of aging of young adults

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Sat Oct 10 07:28:36 EST 1998

William wrote:

> Do you think it is possible that the reason why people start to age at
> an accelerated rate when they reach the age of lets say 50 or so years
> old is because by then the telomeres in their cells have shortened
> enough to actually start making them age? 

Certainly it's possible.  However, as yet there has been no success in
identifying a specific mechanism for how shortened telomeres would have
this effect.  (Such a mechanism might be, for example, an increase in
free radical production in short-telomered cells, caused by decreased
expression of an enzyme involved in mitochondrial maintenance.)  Nor has
a mechanism been identified for how short-telomered dividing cells might
be toxic to non-dividing (hence, presumed, long-telomered) cells.  (Such
a mechanism might be that the short-telomered cells begin to make free
radicals at their surface, which increases oxidative stress in the blood
stream and thence in all cells: this is similar to my proposal regarding
the toxicity of mtDNA decline.)

The failure to identify such a mechanism so far is not a particularly
good argument that no such mechanism exists, of course.  A much stronger
one would be to demonstrate the absence of such a mechanism by showing
that organisms with abnormally short telomeres in all their cells don't
age any faster than normal.  This has not quite been shown by Greider's
telomerase knockout mice, but (as you've seen in past threads) it very
nearly has, since no cells have been found in those mice whose telomeres
are restored to normal length (in embryogenesis) by other means.  Now,
it is possible to say that we haven't yet identified the critical cells;
thus, again the "proof" is not conclusive.  It could be strengthened yet
more if we cloned the gene(s) responsible for the recently-identified
"ALT" pathway of telomere extension, and made mice in which both that
system and telomerase are inactive, and they also aged at a normal rate;
but yet again that would not be a proof because there might be yet a
third telomere extension system.

I hope this makes you wonder how science ever progresses at all.

Aubrey de Grey

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