decreasing proliferative capacity theory

Dr. Sydney Shall sydney.shall at
Fri Feb 9 08:09:32 EST 2001

Iuval clejan wrote:

> Does anyone know any arguments against the theory stating that the main
> cause of aging is the decreasing proliferative capacity of most cells as
> they differentiate away from stem cells. I think this theory is a
> generalized telomere shortening one, saying that telomere shortening is
> not necessarily the cause of decreased proliferative capacity, but is
> correlated with this unidirectional differentiation, and the decrease in
> stem cells (?) may be due to changes in e.g. extracelllular matrix. (Is
> it true that it is not the case that stem cells have a decreased
> proliferative capacity with time, but that there are less stem cells and
> more differentiated cells, and the more differentiated a cell is, the
> less its proliferative capacity?)

The response is that the stem cells may have such a large regenerative
capacity that the loss of the committed, differentiated cells should not
matter.  If they get damaged then the stem cells can just supply some more.

One needs to apply this notion to the stem cells themselves.  Then it is
plausible, I think.

However, in Science last week there were two papers from the MRC labs at
UCL in London England, which reported that although fibroblast cells did
senesce, glial and oligodendocytes did not!!!!!

A remarkable result.

In last week's Nature Thea Tlsty has a paper that says that cells
eventually do senesce.  The field is once again confused with data!!!

Have fun

Sydney Shall

> I suppose this is coupled with the idea that there is a constant
> fraction of damage that escapes repair, and that while there is a good
> supply of stem cells (and perhaps descendants which still have some
> proliferative capacity), cells escaping damage repair are replaced, but
> when proliferative cells run out, damage accumulates.
> -Iuval

-- Dr. Sydney Shall, Department of Molecular Medicine, King's College
School of Medicine & Dentistry, The Rayne Institute, 123 Coldharbour Lane,
LONDON, SE5 9NU, TEL: 01 71 346 3126; FAX: 01 71 733 3877, E-Mail:
sydney.shall at


More information about the Ageing mailing list