Thanks very much for posting the interesting and facinating
information! At least now we know that telomerase "Knock Out" mice do
not invalidate the telomeric theory of aging.
I do have a couple of questions though. If you would answer them I
would greatly appreciate it:
1) Since we now know that telomere shortening probably does have a
negative effect on the aging of mice why doesn't an organization,
university, or company make some telomerase (Knock-In) mice that would
have telomerase activiated in all of their cells?
If this was done we could see if the elimination of telomere
shortening from the mouse could rejuvinate them or keep them from
aging past the optimal healthy point of their life.
Once I read somewhere that a mouse would not be the best organism to
try and immortalize through some form of telomeric therapy. But we now
know that telomeres do shorten in mice and that the reason why "Knock
Out" mice without telomerase do not have problems is because they have
another gene that regulates their telomeres. So it seems to me that it
would be a very interesting experiment to see if we could increase the
life span or rejuvinate a mouse through some form of telomeric
2) If scientists inserted the telomerase gene into the cells of a
mouse would it enlongate the telomeres of the mice or would the gene
that mice have that regulates telomere length possibly block the
Thanks for posting your interesting and facinating article! Keep up
the great work!
Have a great day.
On 7 Sep 1998 04:54:03 GMT, excelife at earthlink.net (Excelife) wrote:
>IV. CRITICISMS, NEGATIVE FINDINGS & OBSTACLES
>>>A) THOSE DAMN MICE AND THEIR LONG TELOMERES
>>>The mouse species Mus musculus has given the telomeric theory its biggest
>headache to date. The length of their telomeres had been measured as being
>substantially longer than those found on the chromosomes in human cells yet
>their life span is only a tenth that of humans. Just how could telomeres be
>linked to aging with discrepancies like this?
>>And then Dr C. Greider did an excellent series of experiments where the gene
>coding for the enzyme telomerase was "knocked out" and the mice not only
>survived for up to six generations but showed no observable changes in the
>life span of the different generations. If telomerase wasn't available to
>restore telomeric length but the mice still survived then perhaps telomeres
>aren't involved in aging.
>>A very typical argument against the telomeric theory of aging would go
>something like this response recently posted in the newsgroups; "Note that
>the telomerase knock-out mice had normal life spans for *six* *generations*
>of steadily decreasing telomere length. The only apparent effect was that
>the sixth generation was sterile.", "...the important point is that the life
>span was no different from that of the mouse strain that the knock-out line
>>Well, I'm happy to report that these legitimate questions have been
>substantially answered in favor of the telomeric theory of aging!
>>As to why Dr. Greider's mice, with the gene that codes for the enzyme
>telomerase deleted, could survive for six generations with no difference in
>life span, is easily resolved. The critics, like above, just assumed that
>all the telomeres in the mice were not being maintained in the absence of
>>Recent studies have shown that this is not the case! Some gene(s) on distal
>chromosome 2 of Mus musculus, Mus spretus, and presumably other mice,
>regulate telomeric length in these mice. These Gene(s) are unrelated to
>telomerase and their products and actions await determination of exactly
>which gene(s) are involved. By determining telomeric length in somatic
>cells, in the absence of telomerase, little difference would be expected in
>the functioning and life span of these cells, nor the life span of the mice
>themselves across the generations.
>>Those cells that normally require telomerase, like the germ cells, in Dr.
>Greider's knock out mice, are affected by the absence of the gene coding for
>telomerase. After around six generations the telomeres in the germ cells are
>too short to support additional replications and the mice are sterile. But
>the cells not requiring telomerase had their telomeres replenished during
>embryonic development of each generation by the genes described above.
>>The answer to the first question, why the mice and their cells die with such
>long telomeres, was also amazingly simple. It seems that some mice
>chromosomes have significantly shorter telomeres than the other chromosomes.
>Their length is such that they could cause a cell to enter senescence after
>approx. 10 population doublings, which is exactly what is observed in the
>studies of the mice. Yeast studies have shown that the loss of a single
>telomere can result in cell-cycle arrest and chromosome loss. Further test
>to determine which genes are on these mouse chromosomes, their functions in
>the cell and their relation to senescence and cellular death do have to be
>conducted but this does appear to be the answer to this question.
>>With the issues involving Dr. Greider's knock out mice substantially resolved
>there are no other major research studies that argue against the telomeric
>theory of aging being a valid hypothesis.
>>There are, however, many other questions and problems yet to be resolved.
>>>(Next: The Major Criticisms)
>>>>>Thomas Mahoney, Pres.
>Lifeline Laboratories, Inc.