IUBio Biosequences .. Software .. Molbio soft .. Network News .. FTP

Major Criticisms of The Telomeric Theory

Tom Matthews tmatth at netcom.ca
Sat Sep 12 19:14:10 EST 1998

Excelife wrote:

> Most unicellular species
> like Budding yeast (S. cerevisea), and most mammals, (in their germ cells),
> utilize the enzyme telomerase to maintain their telomeres.  This enzyme adds
> telomeres to the ends of the chromosome but if the cell in which it is active
> replicates too fast the telomeres can be shortened faster than telomerase can
> replace them and the cell may eventually enter senescence, (see I. Theory E.
> Telomeres and Senescence).

I should have asked about this before, but can you provide us data about
the *amounts* of telomere length which is lost during cellular division,
and also data about typical *rates* at which telomerase can relengthen
telomeres. It appears more and more that major portions of the Telomeric
Theory of Aging highly depend on this data. I don't think "hand-waving"
about these amounts and rates is sufficient any longer.

> Other organisms like the mosquito (Anopheles
> gambiae), utilize DNA recombination to maintain telomeric length

Please describe in more detail. How does this differ from the DNA
recombinations in meiosis? And why can't meiosis maintain telomere
length (without telomerase) by the same process?

> and as we
> have already seen in the mouse (Mus musculus), genes in the DNA can have an
> effect on determining telomeric length.

Maybe sufficient detail is in the papers on this, if/when I get around
to reading them, but at the moment I still reserve judgement on this
until the explanation and mechanism is more elucidated.
> But what does this have to do with aging and the criticisms of the telomeric
> theory?  Well, each of these processes determines how the organism "ages".

I don't understand want you are saying here. Each of these process has
"something to do with telemeres", but that is *not* equivalent to "how
the organism 'ages'".
> For most unicellular organisms, utilizing telomeres to maintain telomeric
> length, their telomeres are fully maintained during mitotic division and
> theses organisms are essentially immortal.

Question: Have any experiments been done on any such organisms to
attempt to "speed-up" mitosis so that the rate of telomerase activity
might not be sufficient for full telomeric length maintenance?

> Budding yeast (S. cerevisea), are an exception to this in that they go
> through assymetric mitotic division.  The mother cell of the yeast then age
> much in the same manner as most other eukaryote cells. Austriaco NR Jr, at
> The Massachusetts Institute of Technology has demonstrated how the telomeres
> in the mother cell regulate the silencing machinery of the genes to control
> aging in these cells.

So could it be, in essense, that rate of division is two fast for the
telomerase to act on *both* sets of chromosomes, therefore the mother
cell has decided (by evolution) to sacrifice the chromosome set which
she retains in favor of the chromosomes set which she gives to the
daughter cell. Again the idea of an experiment to speed up the process
so that even the daughter cells do not have fully lengthed telomeres,
comes to mind.
> So if worms and flys age and die without losing telomeric length and the post
> mitotic cells in humans don't have shortened telomeres just how can telomeric
> shortening be a cause, let alone the controlling factor, of aging in humans?
> Some research has shown that extending telomeric length by introducing
> h-TERT, the catalytic protein subunit of the enzyme telomerase can cause
> human replicating cells to survive well beyond their expected Hayflick limit,
> in a phenotypically youthful state.  But this may be a fluke and not
> applicable to aging.

And these cells are not undergoing the *passage of time* and other
extracellular influences which ages cells in vivo.
> Other research has shown that the loss of telomeres can result in the loss of
> cellular mass in organ systems of the body but this could be an aberration
> and not applicable to aging.

Or it could simply be a correlation with aging (passage of time)

> Still other research has shown telomeric length to be a controlling factor in
> the senescence of cells in the human body but this too may not be related to
> aging.

Because it may not even be related to these cells accumulating an aging

> Cells cannot survive without maintaining telomeric length but they can't
> survive without cell walls either so this may not relate to aging.
> Maintaining or adding telomeric length allows replicating cell lines to
> become immortal but that could lead to cancer and probably has no relation to
> aging.

Ulitmately, it certainly is relevant to aging, but perhaps not until we
first correct other more direct causes of essential human morality and
current maximum lifespan.
> And the fact that telomeric length may be involved in age related genetic
> expression probably has little to do with organismic aging.

I would certainly not agree with this logic, but we first must show that
telomeric length *is* "involved in age related genetic expression".
> So maybe I do agree with the critics, that telomeric loss over age is
> unrelated to aging.

Maybe we will make a "non-telomerist" out of you yet! (Sorry, I just
couldn't resist :-)

Thomas, I don't think that anyone here or anywhere else is trying to say
the telomeric loss it not relevant to aging, *in general*. The important
and contentious question is whether it is the relevant to any current
causes of human mortality, especially those taking place in old age.

Tom Matthews
The LIFE EXTENSION FOUNDATION - http://www.lef.org - 800-544-4440 
A non-profit membership organization dedicated to the extension
of the healthy human lifespan through ground breaking research,
innovative ideas and practical methods.
LIFE EXTENSION MAGAZINE - The ultimate source for new
health and medical findings from around the world.

More information about the Ageing mailing list

Send comments to us at biosci-help [At] net.bio.net