Telomeric Theory - Related Research - Genes & Aging

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V. RELATED RESEARCH


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.


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