IUBio

centromeric shrinkage as a basis for ageing?

Daniel J Housman house at athena.mit.edu
Tue Jun 9 20:22:50 EST 1992


	In reading an article in the New York Times today I learned about 
telomeric shrinkage which may be the basis for some new anti-cancer drugs.
I found this particular article interesting because it deals with a possible
mechanism that may explain some of the molecular basis for aging.
	Apparently there is a code at the end of the telomere, a repeat
sequence which shortens with each passing cell division. The telomere is 
the tip of the chromosome and was referred to as a metaphor to bookends. 
Gene increase has been precedented in growth of a gene such as myotonic 
dystrophy or fragile x until the gene becomes pathogenic and then amplfies
in pathogenicity during following generations. If it is possible for a gene
growth of a repeat sequence to be pathogenic then it may be possible for a 
repeat sequence shrinkage to be pathogenic as well. When the telomere shrinks
below a certain size it is found that in metaphase the chromosomes stick to
each other as they are less tightly bound in their chromosomal matrix. This 
stickyness causes the chromosomes to get caught on each other and probably 
cause severe mutations in cells that divide too many times. 
	Certain cells such as non-organismal cells like amoebas and their kind,
as well as mamalian germ cell lines have a gene expressed which protects it
from the telomeric shaving from one generation to the next. This gene is called
telmerase. This may explain why germ cell lines do not exhibit the symptoms
that have been attributed to DNA damage and have been previously explained by
some sort of super repair mechanism in the germ cells. The clock so to speak
is genetic and so is a good candidate since radiation causes mutations like 
deletions and especially during metaphase. I refer to this because radiation
is one of the forms in which we see a definite mimicking of major portions of
the aging process. If radiation causes mimicked aging then it ought to be a 
genetic clock of some sort. Besides we already know that DNA is getting credit
for everything but the kitchen sink in biology today and is a good contender 
for the aging regulator crown as has been dicussed in discussions about repair
and other things. 
	I don't have a vast knowledge of these telomeric shrinkages and would
request that anyone researching them produce a list of sources for my help in
looking into this possibility. There are plenty of experiments that could be 
done to test hypotheses that include telomeres as the agent of aging since the
length of the repeats on the ends of chromosomes are readily measurable. Also
of note is that Huntington's disease, an elusive gene hiding on the tip of
chromosome four, is neat to the telomere and is expressed as a disease late in
life. Aging though is complex and I wouldn't expect more than senescence to be
covered by a theory like this, but I leave you all with the telomeres to munch 
over if you ever get finished talking about science fiction and medicade.

Dan Housman
MIT '95
 




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