Major Criticisms of The Telomeric Theory

Excelife excelife at earthlink.net
Sat Sep 12 01:54:22 EST 1998


In article <35FA00EE.553F0C0A at nospam.com>, james at nospam.com says...
>
>
>I don't know that I've read the stuff by Austriaco (what's the paper 
>title?), but I would like to point out that this statement you make as fact 
>is far from accepted by everyone.  In fact, I would hope that Austriaco 
>doesn't really put it the way you did because we have no idea what aging 
>*is* in yeast, so we can't possibly know what is controlling it.  In fact, 
>some people would speculate that it is a physical phenomenon, or at least 
>partially physical (as oppsed to genetic) so the whole idea of "genes to 
>control aging" is inapplicable.
>
>Yes, there is some correlation between age and loss of silencing at certain 
>loci (rDNA or mtDNA, I forget which at the moment), but we are far from 
>knowing what this means.


The following is the abstract of his report;

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Proc Natl Acad Sci U S A 1997 Sep 2;94(18):9768-9772

Changes of telomere length cause reciprocal changes in the lifespan of
mother cells in Saccharomyces cerevisiae.

Austriaco NR Jr, Guarente LP

Department of Biology, Massachusetts Institute of Technology, 68-280, 77
Massachusetts Avenue, Cambridge, MA 02139, USA.

Budding yeast cells divide asymmetrically, giving rise to a mother and its
daughter. Mother cells have a limited division potential, called their
lifespan, which ends in proliferation-arrest and lysis. In this report we
mutate telomerase in Saccharomyces cerevisiae to shorten telomeres and show
that, rather than shortening lifespan, this leads to a significant
extension in lifespan. This extension requires the product of the SIR3
gene, an essential component of the silencing machinery which binds to
telomeres. In contrast, longer telomeres in a genotypically wild-type
strain lead to a decrease in lifespan. These findings suggest that the
length of telomeres dictates the lifespan by regulating the amount of the
silencing machinery available to nontelomeric locations in the yeast
genome.


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>Just a note here:  All organisms (with linear chromosomes) maintain at least
>their gamete telomeres somehow.  Drosophila don't have telomerase, but they 
>do use homologous recombination to add repetetive sequences.

Quite correct.  As I mentioned in my post Drosophila melanogaster have a 
different "telomeric structure".  These consist of retrotransposons termed 
TART and HET-A.


>> Cells cannot survive without maintaining telomeric length but they can't
>> survive without cell walls either so this may not relate to aging.
>
>Tom - I can't believe you said that!  Are you feeling OK???  Seriously 
>though, this is just the king of critical thinking that many people would 
>benefit from, and I applaud you making a very valid analogy here.


Thank you.  This is a legitimate analysis of this particular concept.  And 
similar questions can be raised regarding each of the other research findings 
relating to the telomeric theory of aging.  Without a single definitive 
research study to *prove* that telomeric shortening is causative or at least 
related to aging we can only rely on the weight of these studies taken as a 
whole.

In that light the evidence is increasingly pointing to telomeres as being a 
very significant factor in human aging.  The purpose of the telomeric theory 
is to make predictions and direct research efforts that will ultimately prove 
or disprove this theory.



Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.
http://home.earthlink.net/~excelife/index.html





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