>> In article <35EDE86E.10F2 at netcom.ca>, tmatth at netcom.ca says...
>> >> >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
> >> study addressing your question would be Effros RB, Pawlee G, Immunology
> >> Today, 1997, 18;(450-454) where she researches the Hayflick limit and
> >> exhaustion.
> >Unfortunately, the first has no abstract on medline and the second is so
> >brief that it is useless. I will have to consult the articles themselves
> >sometime to see precisely what they found.
>> Tom, I'll try to get my copy scanned and send it to you.
No need. Aubrey sent me a note telling me that the AJHG reference full
text was available online FREE!
It is at:
I just read it. It is a great article. And now I have to agree that
there is *very* strong evidence that replicative senescence is a major
factor in the reduced immunocompetence of many elderly people. Based on
the wealth of detail in the article, I have several thoughts about how
one might aleviate this problem. BTW, T-cells senesce even though they
*do* express telomerase -- they just don't seem to know how to use it
> Her subsequent work has gone on to describe how replicative senescence can
> cause immune exhaustion and that "the proportion of replicative senescent T
> cells within individual subjects may serve as a measure of 'immunological
> age'." It's exciting work that I'll be following closely.
Yes, I will too. Immune decline has always been a major concern of mine
and I do everything that I can to keep my immune system in peak shape.
As a result, I am never sick. Now I must examine carefully what I am
doing to make sure that it is not causing any overstimulation and
overproliferation of T-cells, thereby trading off current and continued
competence for earlier immunological exhaustion.
> Someone whos' immunological system has been stressed to the the point of
> telomerase being unable to maintain telomeric length in the T cells may
> experience a decline or "aging" of their immunological system.
My reading of the Effros paper was that even though T-cells make
telomerase, it did not seem to do any good since there hayflick limit
was only 25-40 doublings anyway. Also, the article pointed out that the
accumulation of senescent memory cell which are also resisted to
apoptosis is a major problem since if they would only die off, they
could be replaced by new younger ones (generated from stem cells as I
understand it). My question to this is why won't either donations of
blood or development of a method to process the blood of the aged and
remove the senescent cells help to solve this problem?
> Someone else
> who has a poor diet, high blood pressure and is overweight may stress the
> cardio-vascular system to a greater degree than the immunological system.
> Whichever, (replicative), cellular system is stressed the most and has has a
> high cellular turnover will experience telomeric shortening and an increased
> proportion of senescent cells to a greater degree than other less stressed
> systems. This is a likely cause of some age-related diseases.
The kind of system-differential aging is, of course, the norm, but it
does not imply that cell senescence is involved in any other system.
> >> >> Tahara H, et al, at Hiroshima University School of Medicine, Japan,
> >> >> demonstrated that "a significant proportion of WRN, (Werner's
> >> >> cell strains showed drastic shortening or lengthening of telomere
> >> >> 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.
> >Just as correlation is not cause, so too "fully conforming" is not proof
> >or verification.
>> Every piece of the puzzle moves us a little closer to understanding aging.
> If it didn't conform to the theory then we'd have something to worry about!
>> By the way, just how do the oxidative stress theories account for these
Tut, tut Tom! You can't win your arguments that way :)
You have mixed up the logic here. From what I understand, I will *agree*
that telomeric shortening is a major cause of death in progeria and
Werner's and perhaps that oxidative stress has nothing essential to do
with it. However, this still say nothing about cause of death in normal
To be very clear, oxidative stress need have no relevance to progeria
and Werner's for it to still be a major cause of death in normal aging.
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