Telomeric Theory of Aging
excelife at earthlink.net
Wed Aug 19 17:40:08 EST 1998
In article <jstrout-ya02408000R1908981330050001 at news.ucsd.edu>,
jstrout at ucsd.edu says...
>In article <35daf0c8.354067837 at nntp.ix.netcom.com>, ufotruth at ix.netcom.com
>>I have a question. I have heard lately of the creation of telomerase
>>"Knock Out Mice" that have the gene for telomerase removed from them.
>>Do you think it is possible that mice could be created or genetically
>>engineered that had the telomerase gene in every single one of their
The gene for telomerase is already encoded in the DNA but when most cells
terminally differentiate that gene is no longer expressed. As noted below,
by Joseph Strout, mice, particularly mus musculus, may not be the best
candidate to test this experiment. Telomeric length in these mice are not
only regulated by telomerase but also by an unrelated genetic component on
chromosome 2.(Proc Natl Acad Sci U S A 1998 Jul 21;95(15):8648-8653 "Telomere
length regulation in mice is linked to a novel chromosome locus.")
Many other mammals more closely compare to the human model of telomeric
shortening leading to cellular senescence and presumed aging of the organism.
Our knowledge of how to intervene in age related expression of specific genes
is extremely limited so methods to re-activate the telomerase gene are not
However, extra-nucleic expression of factors that can maintain telomeric
length have been demonstrated. First by utlizing the RNA components
associated with telomerase, (Nat Genet 1997 Dec;17(4):498-502 "Reconstitution
of human telomerase with the template RNA component hTR and the catalytic
protein subunit hTRT".) Secondly, dispersed DNA coding for the T2AG3
telomeric repeats has been found in immortal cells not expressing
telomerase,(Biochem Biophys Res Commun 1998 Jul 20;248(2):223-227 "Release of
telomeric DNA from chromosomes in immortal human cells lacking telomerase
Utilization of these procedures in mammals that age more like humans may
answer the question of whether extending telomeric length in vivo will also
extend the life span of the organism.
>As I understand it, this isn't necessary -- mice die of natural causes way
>before there telomeres have shortened significantly. So the experiment you
>describe has basically already been done, by Nature.
Possibly, but no definitive study has been done to determine whether
telomeric shortening is a causative factor in the death of mice. The long
telomeres of of mus musculus, the telomerase knock-out mice studied by Dr. C.
Greider and the fact that mouse cells do not experience telomeric related
senescence do suggest a different progression of cellular development but do
not described any alternative cause of aging in mice. In fact one study of
mouse telomeres shows that some chromosomes have significantly shorter
telomeres than the other chromosomes, (Proc Natl Acad Sci U S A 1997 Jul 8
94:14 7423-8 "Telomeres in the mouse have large inter-chromosomal variations
in the number of T2AG3 repeats"). Yeast studies have shown that the "loss of
a single telomere results in cell-cycle arrest and chromosome loss", (Nat
Genet 1998 Jan 18:1 76-80).
Without further research we cannot rule out telomeric loss as being a
causative factor in the aging of mice.
Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.
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