Telomeric Theory of Aging

Excelife excelife at
Wed Aug 19 04:07:37 EST 1998



A) The Basic Theory

The basics of the theory are elegantly simple.  Telomeres at the ends of the 
chromosomes in dividing somatic cells shorten every time they go through 
mitotic division  When the telomeres in these dividing cells become too short 
the cells enter a senescence stage, stop reproducing and eventually enter 
crisis stage and die.

B) The Primary Hypothesis

The main hypothesis of the telomeric theory of aging is that this telomeric 
limitation on the replicative ability of dividing cell lines is the primary 
cause of aging and age related diseases.

C) Telomeres and Age-Related Diseases

The mechanism of of going from telomeric loss and subsequent cellular 
senescence to causing organismic death has not yet been proven but there a 
several very good theories on how this could occur.

Some cell lines, in vital bodily systems, which are subject to excessive 
oxidative stress, free radical damage and various environmental factors, will 
have a higher replicative rate than other, less stressed, bodily systems.  
This higher  cellular turnover results in the cell lines of that particular 
system losing telomeric length, entering senescence, crisis stage and death 
at a faster rate than the rest of the body.

This is, apparently, what occurs with some of the endothelial cells lining 
the arteries and veins.  When these cells enter senescence they produce 
excessive free radicals and collagenases.  The resulting damage to the 
cellular membranes and matrix, along with the thinning of the walls of the 
arteries and veins resulting from cellular loss, are thought to be the major 
contributors to atherosclerosis, plaque formation, thrombosis, and heart 
disease in general.

Alternatively, other vital bodily systems may be subject to greater stresses
than the vascular system in some individuals.  For example, when stem cells 
producing T-lymphocytes, the primary weapon of the immune system, are 
responding to an infection they undergo numerous replications.  Because the 
enzyme telomerase is present in these cells they are able to continue 
producing the T-lymphocytes without regard to the Hayflick limit associated 
with cells without active telomerase.  However, with rapid replication the 
telomeres in these stem cells still shorten at a faster rate than the enzyme 
telomerase can replace them.  When the telomeres become too short the stem 
cell can no longer produce the T-lymphocytes and with sufficient stem cell 
loss the entire immune system can become impaired.

Many, if not most, cancers are thought to be the result of cells by-passing 
their normal senescent and crisis stages reached as a result of telomeric 
loss.  Cancerous cells undergo numerous changes one of which is believed to 
be the reactivation of the enzyme telomerase.  The reactivated telomerase 
stabilizes the telomeres at the ends of the chromosomes and allows the cell 
to re-initiate mitotic division.  So long as the enzyme telomerase is active 
in the cancerous cell it is basically immortal and this allows the cells to 
build into a tumorous growth.

These are just some possible ways that telomeric loss can be the underlying 
cause of age related diseases and the resulting organismic death. The 
telomeric theory of aging suggests that intervention in some of these 
processes by enabling cells to maintain or replace the telomeres at the ends 
of the chromosomes we may be able to stop or even regress some of these age 
related diseases.

(Next: Telomeres and their effect on aging in general.)

Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.



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