Telomeric Theory - Related Research - Genes & Aging

ufotruth at ufotruth at
Fri Oct 2 15:36:41 EST 1998

Tom Mahoney,

Thanks very much for you latests very interesting and informative
post. It was very interesting and I really think you need to keep on
posting them!

But I am wondering about something. According to what I have read
cells in-vitro start to "age" as they divide many times before they
even reach senecence. More specifically I have read in the book "How
and why we age" by Leonard Hayflick that eventually, after a cell has
divided many times, it starts to divide less quickly, looks "older",
functions differently, and changes in other ways. In your post you
mostly talked about age related genetic expression in cells that have
turned senecent. But what about cells that have divided many times,
and have grown "old" but are not yet senecent? Are age related genetic
changes being expressed in them?

Basically, I am curious as to whether telomere shortening causes
changes in cells BEFORE they even reach the point of senecence. You
see from what I have read posted by some individuals on this news
group, and this might be totally wrong, there is no evidence that an
accumilation of senecent cells builds up in individuals as they age.
If this is true then the telomeric theory of aging cannot be valid if
it only causes problems for cells that have turned senecent.

But if telomere shortening can effect cells that have not even reached
the point of senecence, then whether or not there is an accumilation
of senecent cells in older individuals it does not weaken the
telomeric theory of aging because telomere loss could be causing aging
in NON senecent cells.

Do you know if there have been any experiments on older individuals
tissues to see if there is an accumilation of senecent cells?
Personally, in my opinion, it seems very possible that older
individuals could accumilate at least some senecent cells in their
tissues which could cause other cells in the same tissues problems.
But, I do not personally have any verification of this possibility.

Thanks again for the post of yours! Keep up the great work.

Best Regards,

On 2 Oct 1998 07:37:01 GMT, excelife at (Excelife) wrote:

>C. Genetic Effects on Aging
>Another major question facing the telomeric theory of aging is the role and 
>control of age related genetic expression.
>Genes are differentially expressed during various stages of cellular and 
>organismic growth.  There is some evidence that telomeric length plays a role 
>in determining when particular genes will or will not be expressed.  Research 
>into aging of the yeast Saccharomyces cerevisiae through regulation of the 
>transcriptional silencing "machinery" and the process of telomere position 
>effect, "suggests that the length of telomeres dictates the lifespan by 
>regulating the amount of the silencing machinery available to nontelomeric 
>locations in the yeast genome."
>Silencing factors are essential for cell-type specific gene expression and 
>age related genetic expression.  That the telomeres have been shown to be 
>directly involved in a portion of this process holds promise for additional 
>research in this area.
>Specific genes are also involved in the entrance of cells into senescence.  
>The genes ataxia-telangiectasia (ATM) and p53 activate other genes, including 
>p21 and p16, when the telomeres reach a critically short length.  The result 
>of the activation of these various genes is the halt of cellular replication 
>for a long period of time.  The effects of this senescent stage have been 
>previously described and may be one of the major causes of functional 
>declines in organs and tissues associated with aging.
>Since these genes activate the senescence signal only when the telomeres have 
>reached a critically shortened length, these effects may be avoided 
>altogether by a therapy that maintains telomeric length.  The research being 
>currently conducted may answer this question in the near future.
>Other genes have shown a direct effect on longevity and still others have 
>been shown to be differentially expressed as we age.  
>Some of these genes, as seen in Drosophila melanogaster and C. elegans, 
>inhibit the detrimental effects of oxidative stress and allow the 
>post-mitotic cells and thus the the fly and worm to survive for a longer 
>period than observed in normal flys and worms.  In other organisms with cells 
>that are not post-mitotic, this strategy of allowing individual cells to 
>survive for longer periods of time could have the effect of delaying 
>telomeric shortening, due to replication.  This may also allow an individual 
>organism to survive for an extended period of time.  Research into this 
>possibility are continuing.
>Human studies around the world have shown some genes to be related to aging 
>in various populations.  In France it was determined that "The frequency of a 
>genotype known as a cardiovascular risk factor was increased in 
>centenarians."  The Japanese, in a study of long lived Okinawans, showed 
>"that several alleles of the HLA-DRB1 and/or HLA-DQ genes are involved in 
>human longevity."  And a Russian study showed "the daughters born to old
>fathers (50-59 years) lose about 4.4 years of their life compared to
>daughters of young fathers (20-29 years)", suggesting that the paternal X 
>chromosome is involved in longevity determinations.
>None of these studies tested for the involvement of the telomeres in these 
>populations.  Follow-up studies to determine: if senescence is involved in 
>the French centenarians; if transcriptional silencing or un-silencing is 
>involved in the expression of the HLA genes; and if telomeres are shortened 
>on the X chromosome in the germ cells of the "old fathers" in Russia, may 
>produce some interesting results.
>The research into the interactions of telomeres and the genes are just 
>beginning and if the preliminary result are any indication, it appears they 
>will have a substantial impact in determining how the telomeres are involved 
>in aging.
>(Next: Drugs and Supplements)
>Thomas Mahoney, Pres.
>Lifeline Laboratories, Inc.

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