Current Research Into Telomeres III

Excelife excelife at earthlink.net
Wed Sep 2 01:13:17 EST 1998


In article <35ECC85A.513B at netcom.ca>, tmatth at netcom.ca says...
>
>Excelife wrote:
>
>> Dr R. Effros at U.C.L.A. is researching the effects of telomeric >> 
shortening on the T-Cells in the immunological systems of the elderly.   >> 
Her observations include the dominance of senescent "memory" T-cells in >> 
aged individuals
>
>To be precise, are you saying that Rita Effros has found that the
>*majority* of memory T-cells are now longer able to divide and produce
>more such T-cells? Do you have a reference for this?


The cite for this study is Am J. Hum.Gen. 62-5 May 98;(1003-1007).  A better 
study addressing your question would be Effros RB, Pawlee G, Immunology 
Today, 1997, 18;(450-454) where she researches the Hayflick limit and immune 
exhaustion.
 

>> which may "prevent renewal of the T-cell pool with more functional 
>>T-cells".  The implications being that the restoration of replicative 
>>capacity in those T-cells that are approaching senescence could have the 
>>effect of restoring functioning of some parts of the immunological system 
>>in the elderly.

>Or since now you say "are approaching senescence" do you mean that she
>found that the T-cells had reduced replicative ability in older people?
>(which would not necessarily be related to any telomere shortening).


Yes the "memory" T-cells showed senescent characteristics including the 
inability to replicate and the short telomeres associated with senescence.

Specifically a cell surface molecule CD28 is not expressed in senescent 
T-cells.  One proposed function of CD28 is the induction of the enzyme 
telomerase, (Weng et al. J. Exp. Med. 1996, 183:2472-2479).  Lacking the 
expression of telomerase the telomeres in these T-cells shortened and the 
cells entered senescence.

The implications being that re-activating telomerase prior to critical 
telomeric shortening can avoid senescence altogether and maintain functioning 
of the immune system.


>> Rawes V, Kipling D, Kill IR and Faragher RG at The University of Brighton,
>> UK, have demonstrated results that "suggest that the process of senescence 
>> is a common feature of different cell lineages but that the specific rate 
>> can differ between them."
>
>Do they mean different "rate" or after a different number of divisions?


I'm not sure of your exact question here.  They are saying that particular 
cell lines replicate faster than others, lose telomeric length and enter 
senescence at an earlier time.  Because they are the same cell line and have 
similar telomeric length, the cells enter senescence at approx. the same 
time.


>> Thus the cell lines constituting the endothelial cells
>> in the vascular system may be experiencing telomeric loss faster than 
other
>> cell lines in the body.  This may be a factor underlying age-related
>> "disease" progression in some systems of the body.
>
>Certainly, because division "rate" is highly different in different
>dividing systems and under different life, and health (sometimes
>disease) conditions.


Absolutely!  As is seen in T-cells, specifically in HIV patients, where 
T-cells are forced to replicate faster to meet an infection their telomeres 
shorten because the cells are replicating faster than telomerase can replace 
them.


 
>> Tahara H, et al, at Hiroshima University School of Medicine, Japan,
>> demonstrated that "a significant proportion of WRN, (Werner's syndrome), 
>> cell strains showed drastic shortening or lengthening of telomere lengths 
>> during cell passages compared with normal cell strains"  This confirms   
>> earlier  studies that Werner's syndrome and the childhood aging disease  
>> progeria result from errors in the system(s) that maintain telomeric >> 
length.
>
>But it doesn't say anything about whether these diseases are related to
>normal aging.


It fully conforms to the telomeric theory of aging that suggests that if a 
person were born with shortened telomeres their cells would senesce faster 
and they would exhibit the signs of aging.
   
 
>Sorry, to be always playing the "skeptic", Tom.


No need to be sorry!  Skepticism is one of the foundations of science.  One 
should always test for the null hypothesis and only by proving that wrong can 
they make any claim to knowledge.  The more you challenge any particular 
theory the sounder the reasoning to support it has to be.


>I found your post to be most interesting, as usual.


Thank you!  I do try to be informative and accurate.  If I make a factual 
error or mis-state the findings of some research I WANT to be told about it. 
It does me absolutely no good to be operating on false assumptions.  It's an 
old saying that if the facts don't fit the theory then change the theory not 
the facts!



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




More information about the Cellbiol mailing list