Re-Visiting a Post by Lou Pagnucco

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Fri Oct 23 07:58:50 EST 1998


Lou Pagnucco wrote:

> If so, since they can be identified by staining, can they also be
> targeted by smart drugs which have special affinity for these cells
> and selectively toxic to them?

It seems relatively feasible to use either the increased production of
collagenase or that of beta-galactosidase for this purpose.  Moreover,
Tom's earlier objection presumes that there are enough fibroblasts near
senescence that their division (triggered by this selective ablation)
would push as many of them into senescence as were ablated in the first
place, which is wrong, as I have explained in the interminable recent
thread on quiescence.  The propensity of near-senescent cells to enter
apoptosis changes nothing, since that simply triggers MORE division (as
if those cells had been among the ones deliberately ablated).  However,
the point that senescent cells potentially inhibit the production of more
functional cells is of course correct, the mechanism being (guess what)
contact inhibition.  That is why the immune system, which relies so much
on the ability of particular cells to proliferate fast on demand, is (on
current evidence) by far the most likely place where telomere shortening
genuinely may cause a functional decline with age.

A weaker link in Lou's idea is the question of whether these senescent
fibroblasts are responsible for lax skin etc.  It is unclear whether
the overproduction of collagenase would have these effects, since they
are normally ascribed to the disorderly crosslinking of OLD collagen.
Most such collagen should be no less degradable by collagenase than
undamaged collagen, so this overproduction may, if anything, actually
RETARD these features of aging of skin.

Aubrey de Grey




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