Telomeric Theory of Aging
excelife at earthlink.net
Wed Aug 19 04:07:37 EST 1998
TELOMERIC THEORY OF AGING
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
(Next: Telomeres and their effect on aging in general.)
Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.
More information about the Cellbiol