Telomeric Theory - Related Research - Genes & Aging

ufotruth at ufotruth at
Sat Oct 3 22:36:08 EST 1998

>The typical Hayflick progression of cellular aging comprises a period of 
>rapid proliferation until cumulative population doubling level 22 to 24, 
>followed by a phase of slow growth and the final cessation of cell division 
>at 32 to 34 population doublings,(this varies somewhat depending on the type 
>of cell).  This coincides with Dr. E.H. Blackburns' study, (Proc Natl Acad 
>Sci U S A 1998 May 12;95(10):5607-5610), wherein she says "Telomeric repeats 
>are lost rapidly (at a rate of >1 kilobase per year) from the (cells) of 
>young children, followed by an apparent plateau between age 4 and young 
>adulthood, and by gradual attrition later in life."

Thanks for the information. At least we now know that the telomeres of
individuals, at least of humans (who knows about extraterrestrials),
definantly do shorten as they age and grow older. Since we now know
this to be true, and also know that even BEFORE a cell goes into
senecence that it goes through a significant phase of slow growth and
other changes, that telomere shorteing of cells that are not senecent
most probably DOES INDEED cause aging in human beings.

What is also interesting to know is that the normal human cells that
GERON immortalized divided (and may be continuing to divide) MANY
times past their "hayflick" limit and divided RAPIDLY, stayed YOUNG,
and did NOT go into a phase of slow growth. Because of this we at
least know that the aging of cells in the human body, before they even
become senecent, could be stopped if we could immortalize the cells
with the telomerase gene GERON discovered!

Isn't it great that we now know of a way to stop cells from aging with
increasing number of divisions and becoming senecent! :-)

>This is important to recognize when talking about age related genetic 
>expression.  The most dramatic change in gene expression occurs in the first 
>phase of rapid growth when the cells are developing until they terminally 
>differentiate.  While this stage is very important, especially to those 
>investigating the various growth factors, it is not of such great importance 
>for longevity.

I personally think it is very important. If the length of telomeres do
indeed control genetic expression then we need to realize that the
above is VERY important to longevity. Because it seems to me that if
telomeres do control genetic expression then it MIGHT NOT be wise to
lengthen the telomeres of lets say a 60 year old to the lengths of a 1
month old fetus because it could cause UNWANTED genetic expression.

Perhaps just like everything else telomere shortening should be used
in moderation. 

Also, perhaps it is not wise to drink TOO MUCH from the telomeric
fountain of youth!

>The second most dramatic changes in genetic expression occurs at the time the 
>cell enters senescence.  These have been discussed before and I won't bother 
>with the details here.

If the above is true then I am absolutely thrilled. Because the cells
GERON immortalized did NOT grow old in anyway or become senecent at
all! They stayed in a YOUNG and RAPIDLY DIVIDING state! So apparently
by insertion of the telomerase gene you can keep cells from having
this dramatic age related genetic expression from occuring.

>The changes that occur, over time, in the genes expressed or not expressed is 
>what your question is about.  These changes have been noted in "older cells" 
>in most studies I was able to find.  These would, for the most part, coincide 
>with cells in the last stages of approx 32 population doublings.  

Now, I am not questioning your information but in the book I read by
Leonard Hayflick his magic number was not 32 but 50. 

But regardless at least we have now confirmed that cells DO INDEED age
BEFORE they become senecent and by INSERTING the telomerase gene in
cells you can STOP cells from aging as they divide. Actually, you can
even keep them in a YOUNG and YOUTHFUL state!

>I would argue that many of theses changes noted are the result of either 
>senescence in cases like the slowing of population doublings or cellular loss 
>due to apoptosis of cells reaching senescence.  Most of the research into 
>these observations did not control for senescence.  It is likely, therefore, 
>that many of the results achieved were a function of the lost functioning 
>capacity of some of the cells due to senescence.  Actual cellular mass loss 
>would result in similar observations of diminished functioning but this is 
>far less common.

Very interesting. Thanks for the information.

>A striking example of these differences can be seen in the study, (Jacobsson 
>G,,, Mech Ageing Dev 1998 Mar 16;101(1-2):33-41, "Decreased mRNA 
>levels for exocytotic proteins in the pituitary of aged rats."  On the one 
>hand "part of the decrease in the expression of mRNA in the intermediate lobe 
>can be explained by a decreased number of cells per unit area."  Whereas "The 
>decline in anterior pituitary hormone secretion reported in aged rats appears 
>to be paralleled by a down-regulation in mRNA levels for several proteins 
>involved in the molecular regulation."  It is likely, since the study was on 
>aged rats, that the observed silencing of some of the genes for these 
>proteins was the result of senescence in some of the cells involved, although 
>that was not specifically addressed in the study.

It would be interesting if you could take some cells from the
pituitary of a human being, let some of them age, and immortalize the
rest of them with the telomerase gene (to keep them in a youthful
state) and see if the telomerase positive cells produced the proper
and needed ammount of proteins verses the older cells.

Or even better, just immortalize an old cell and see if the level of
these proteins increases.

>Still, studies may show different genetic expression between young and old 
>cells in the absence of the senescent state. (Although my brief Medline 
>search couldn't come up with any, that is more a lack of knowing where to 
>look rather than a lack of studies.)  This seems to be particularly true of 
>some of the enzymes and hormones.  The production of various hormones are up 
>regulated on an age dependant basis and the sudden onset of menopause suggest 
>there is also an age related down regulation.

Well, we know for a fact that as cells divide their dividing slows
down and they age. We also know for a fact that cells immortalized by
GERON stayed young and did not age in anyway. So if age related
genetic expression causes cells to grow old then we now know for a
fact that telomere enlongation through insertion of the telomerase
gene can PREVENT the age related genetic expression that causes cells
to age.

>If anyone in the group has references on studies of this processes, 
>particularly any that might have controlled for senescence, I would 
>appreciate the references to increase my own knowledge.  

I sure would appreciate the information as well.

>The main reasons there is a lack of evidence for senescent cellular 
>accumulation in the elderly is 1) it hasn't been looked for and 2) that up 
>until recently it was extremely difficult to distinguish between senescent 
>and non-senescent cells.  It was in 1995 that Dimri GP, in (Proc Natl 
>Acad Sci U S A 1995 Sep 26;92(20):9363-7, "A biomarker that identifies 
>senescent human cells in culture and in aging skin in vivo.), that they found 
>a means of identifying senescent cells, and determined that there was 
>"evidence that senescent cells may exist and accumulate with age in vivo."

That is very interesting. It seems to me that further testing should
be done to see if there is an accumilation of senecent cells with age
in vivo. If the method of testing was not TOO expensive then perhaps
it could be a project Lifeline Labs could undertake?

>The arguments against the accumulation of senescent cells in the aged are 
>based on a lack of knowledge and research to prove this accumulation.  There 
>is little or no evidence, to my knowledge, suggesting that they do not 
>accumulate with age.

I agree with you.  

>Transcriptional silencing of genes, ie;blocking a gene from being expressed, 
>and conversely un-silencing of genes is the mechanism by which genes are 
>differentially expressed. This is true for different types of cells, in 
>individual cells and in cell lines over age.  The telomeres have been shown 
>to be involved in some portions of these processes.  It is yet to be 
>determined if they are a major or a bit player and the research is 

It seems to me, and I might be wrong, that the answer is very clear.

Normal cells lose their telomeres and age as they divide and then
eventually become senecent. 

Immortalized cells, whose telomeres have been enlongated with the
telomerase gene, stay YOUNG, don't become senecent, and do not age.

It seems to me the answer is clear.

Isn't it great!

>The study cited above and Dr. Effros' work on T cells in the human immune 
>system come immediately to mind.  There is undoubtedly other research that 
>also shows this accumulation but most of the work dealing with senescence is 
>on the cellular and molecular basis.  Most Universities have separate 
>Departments for bio-chemical research and population studies and they seldom 
>co-ordinate their studies.  Bureaucracy at work!

Just like with a big government there is a lot of bureaucracy in some
big universities!

Thanks very much for responding to my post and answering my questions.

Keep up the great work.

Best Regards,
William (on Netcom)

>Thomas Mahoney, Pres.
>Lifeline Laboratories, Inc.

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