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Very odd abstract found. Any comments?

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Thu Sep 10 07:48:28 EST 1998

> Vol. 95, Issue 18, 10614-10619, September 1, 1998

This is Proc. Natl. Acad. Sci. USA, whose full text is available
online.  One can go to the PubMed entry and click on the PNAS logo at
the top.

James wrote:

> But I don't see how cells that are not
> expressing telomerase are maintaining the replicative potential in vivo
> (which is the conclusion I draw from the fact that their replicative
> capacities do not differ significantly when grown in culture), and then
> senescing uniformly in vitro.

to which William wrote:

> Unless the cells in
> the 70 year old male had mysteriously not divided hardly at all over
> the last 60 years or his life, or the 10 year year old had some
> disease which made his cells divide at a VERY fast pace, then
> LOGICALLY and RATIONALLY the cells from the 10 year old should have
> MORE replicative potential than from the 70 year old....

and Tom Matthews wrote:

> I thought that we had already established at some point in these threads
> that skin is generated by some kind of basal stem cells which *do*
> express telemerase. In which case, in healthy skin the *first*
> derivatives of those cells (which replicate outwards to the surface, as
> I understand it) would always have new, unshorened telomeres. Only in
> those cases where skin is diseased and too quickly needing to be
> regenerated, would the basal cells not have time to regenerate their
> telomeres before having to replicate again.

The answer to all these points is that the cell type studied is dermal
fibroblasts.  The cells on the outer surface of our skin (the epidermis)
are generated as Tom describes, but those in the deeper layer (the dermis)
are not.  In fact, they divide VERY rarely (in adulthood -- see below)
unless and until injury of the tissue, at which time they proliferate to
heal the wound.  Thus the non-division that William suggests is in fact
not mysterious at all.

The most frequently cited study showing a correlation of the replicative
capacity of dermal fibroblasts with donor age is Allsopp et al, PNAS
89:10114-10118 (ref 10 in the new paper that William found).  That study
looked at three, not two, variables: the third one was telomere length
at the time the fibroblasts were taken from the patient.  The central
result of the paper was a strong correlation between replicative capacity
and telomere length; the correlations between replicative capacity and
donor age, and between telomere length and donor age, were much weaker.
This is of course to be expected if one bears in mind the above point
that dermal fibroblasts divide extremely rarely in the body.  Unluckily
for them, however, Allsopp et al are often quoted as having shown that
telomeres of dermal fibroblasts shorten in the body at 15 base pairs per
year.  That is indeed what the paper says, but (a) there was a lot of
scatter in the data (just as in this new study) and (b) no account was
taken of the fact that our surface area increases during childhood, which
intuitively requires division of dermal fibroblasts.  If you look at the
relevant graph in Allsopp et al and chop off the first 20 years, it is
clear that there is no significant drop in telomere length with age.  (I
discussed this with Cal Harley a couple of years ago and he agreed that
this interpretation destroyed the validity of the 15bp/year result.)  The
new study has almost no data from donors aged less than 20.

Aubrey de Grey

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