Telomeric Theory of Aging II

[Excelife]

I. THEORY


C) Telomeres and Organismic Aging


This is probably the least studied aspect of the telomeric theory of aging.  
Much of the following are conjectures and hypothesises suggested from the 
research to date.  Future research, (some of which are presented in the 
discussion section),  will help clarify the role that telomeres play in 
aging.

It is possible that telomeric length itself is the single determining factor 
in organismic life span but it is highly improbable.  More likely it is a 
major factor effecting the longevity of replicating cellular systems and a 
contributor, primarily via the aging of the vascular system, to the decline 
in functioning of non-reproducing cells.

Assuming an organism has avoided all prior causes of organismic death its 
life span is still limited by aging itself.  This organismic death manifests 
itself through failure(s) in some vital bodily system but is directly related 
to the body not being able to maintain or replace the cells making up these 
systems.

Since the loss of telomeric length on the chromosomes is the limiting factor 
in cell replication, (in dividing cellular systems), it is logical to assume 
that this is the underlying cause of cellular loss and thus subsequent 
failure of these vital systems.

If a methods are developed to maintain or enhance telomeric length we may be 
able to not only stop the failure of these vital systems but if cellular mass 
can also be replaced we might be able to restore maximum functioning in these 
system and "rejuvenate" the system.

Several related problems would need to be resolved for this "therapy" to be 
effective. First, the rate of mitotic division to restore lost cellular mass 
must be increased.  Merely restoring the replicative capacity of the cells, 
by adding telomeric length, may not be sufficient to actually cause the cells 
to divide to restore the functions of these systems.  It is possible that the 
normally present chemical progenitors of cellular reproduction would initiate 
the process but in their absence the use of various growth factors may be 
required, (more on growth factors under Related Research).
 
Secondly, the problems involving age related genetic expression need to be 
addressed.  Once again, replacing lost cellular mass may not be sufficient to 
assure the appropriate genes necessary to the functioning of the system are 
expressed when and where they are needed.  Some research into the causes and 
failures of genetic expression are currently being conducted and telomeric 
length itself may play a role in controlling genetic expression but much 
further research is required in this area.

Finally and most troubling are the problems related to aging and death of 
non-reproducing cells, most notably nerve and muscle cells.  Extending 
telomeric length would have no direct impact on the aging of these cellular 
systems.  There is the possibility that if the vascular and immune systems of 
the body were restored through telomeric lengthening then there could be a 
beneficial effect on these non-dividing cells.  It is believed that other 
than oxygen or sugar deprivation or an inability to rid itself of waste 
products, there is no reason for a nerve cell to die.

Other non-dividing cells may be subject to mitochondrial aging related to 
oxidative stress and alternative strategies may be required to address these 
problems, (see more under Related Research).

This is just a brief overview of how the telomeric theory of aging is 
possibly involved in the process of organismic aging but the picture will 
become much clearer and perhaps need to be revised as the research results 
come in.


(Next: Background of the Theory)