15 replies to this topic

[olaf.larsson]

All stem cells have active telomerase right?

[John Schloendorn]

Yes. By definition a stem cell can self-renew indefinitely and there is no way to do that but with telomerase.
Well, there is one, namely ALT, which is active in some cancers. But it confers genomic instability and is not known to be active without cancer. So if you count cancer-stem cells, there might be some telomerase-negative, but ALT positive ones.
(I just posted some related points in the journal club.)

[John Schloendorn]

During aging, telomerase levels and telomere lengths decline in many stem cells, which is thought to contribute to their age-related exhaustion.

[olaf.larsson]

How could it be then be said that telomere shortening is important in aging?
If stem cells have telomerase they could replace old telomere short cells with new ones.
I rather suspect that stem cell mutations are important.

[olaf.larsson]

Are there any experiments done yet in which old animals are infused with their own young (frozen down) stemcells? You could add to this the killing of the old stemcells by some selective mechanism.

[John Schloendorn]

In mice you don't need to use the animals' "own" cells, because the frequently used strains are all in-bred for many generations and thus share the same histocompatibility alleles. But still, young donor to old recipient transplantations are very rare. See e.g. Gary van Zant's work on the hematopoietic system, thanks to Prometheus available here.
Transplantations with stem/progenitor cells derived from embryonic stem cells (which is also a form of young to old transplantation) are more frequent and easily found on pubmed. But in many tissues, the teratoma problem has not been resolved.

[olaf.larsson]

If stemcells have active telomerase and stemcells can replace old worn out cells by newones how could it be that telomeres of old people are said to be shorter than those of young people?

[John Schloendorn]

During aging, telomerase levels and telomere lengths decline in many stem cells, which is thought to contribute to their age-related exhaustion.

Plus:
There may be other causes (other mutations, hormone signalling, extracellular matrix changes, niche cell dysfunction), that also contribute to the decline of stem cell numbers with age. This of course puts more stress on non-stem somatic cells, because they get less frequently renewed (and stress can shorten telomeres).
All in all, the idea that the same telomere gets progressively shorter over the life-span seems pretty wrong. It's all a highly dynamical thing.

[olaf.larsson]

Where I live scientist including human geneticist and cancer specialists seem to "know" that aging is caused by telomere shortening. I would rather say that telomere shortening invivo its sideeffect which can eventually kill the cells.

[John Schloendorn]

Now to say that aging is being "caused" by one particular thing is indeed audacious. Are you sure you got that right? What do these say if you ask them just how it "causes" it? How do they interpret telomerase-overexpressing mice with long telomeres and slightly shortenend life-span?

[olaf.larsson]

Well if you are not acctually into the aging processes I guess you belive what is written in the popularpress about it. I doesn´t feel easy for me to say to people that have done biology for 35 years that they are wrong and I know better how it really is. Interessting is that teleomerase knock out mice have the normal phenotype for sevral generation. That would mean that telomere shortening has no effect on aging invivo.

[Mark Hamalainen]

Where I live scientist including human geneticist and cancer specialists seem to "know" that aging is caused by telomere shortening.

I too have heard this from scientists who don't study aging. Unfortunately, this misconception is very widespread and well entrenched.

[Mondey]

Hi all,

This experiment has been done, but not quite in the way you wanted it to be done (I guess). In one paper [Dressler et al., 2005 ] they claimed to have frozen stem cells of a rabbit and injected them back into the same old animal (into the tendon) and measured the repair. The old stem cells are supposed to regenerate the tendon as good as the young stem cells. But they did not look for engraftment of the young stem cells in the old animal as control.


Not all stem cells have active telomerase. The expression in some stem cells is still under discussion.
In addition, some stem cells seem only to have active telomerase for short period of times (see haematopoetic stem cells). And even when telomerase is active, this does not mean that not telomere shortening can occur. In blood stem cells it was shown that despite them being sometimes telomerase positive they loose telomeres. Some studies have also shown that oxidative stress can increase telomere shortening by introducing single/ double strand breaks, which shortens the telomeres with the next round of replication even faster. Telomerase activity under high stress might not be sufficient to stabilise telomeres

To the discussion about aging researcher. Sure they say they know why aging occurs and how it occurs, as only then they will get many. It is either my theory (my money) or your theory (your money).

Greetings

Edited by Mondey, 03 August 2005 - 08:42 PM.