Current Research Into Telomeres III

Aubrey de Grey ag24 at
Mon Sep 7 08:47:04 EST 1998

> My mistake. I thought that except for DNA, *all* other molecules where
> *eventually* recycled. If they are not, it seems to me that causing such
> should be easier than gene therapy to effect DNA aging changes.

My guess is that yes, it would mostly be easier than most gene therapy,
but that *mitochondrial* gene therapy is an exception - it could be the
easiest of all.  This is largely because there are only 13 genes to rescue,
rather than 50-100,000.  Some very impressive progress has been made in
recent years in reversing some of my list -- particularly AGE cross-links
in collagen (Vasan et al, Nature 382:275-278) but I would be surprised if
some of the others don't prove a lot harder.

> > - glands which shrink with age due to slower cell division than death
> Isn't this last one really "derivative" of whatever is causing the
> "slower cell division than death"? which in turn would likely have a DNA
> cause. 

That depends whether the shrinkage would happen in the absence of any of
the other "ultimate" changes.  I included it because my guess is that, in
this regard, it is like telomere shortening -- the genetic capability to
reverse it is present and correct but is not used, and moreover its non-
use is intrinsic, not an aging response (derivative of other age-related
degeneration).  So yes it has a "DNA cause" in the sense that the reason
for the shrinkage is due to genetic regulation of cell division, but it's
not a "DNA damage cause", so it's still in my "ultimate" category.

> Just to clarify, I assume you mean that "each" of the derivative
> changes are driven by *all* the ultimate ones.

Yes -- to a greater or lesser (including infinitesimal) extent.  Sounds
like a truism put like that, I know, but the point is that the derivative
ones don't contribute ANYTHING -- if all the ultimate ones were totally
eliminated, the derivative ones would be eliminated too.

Aubrey de Grey

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