FWD>RE>Premature Ageing

Mike West mwest at geron.com
Wed Apr 10 17:25:24 EST 1996


Mail*Link( SMTP               FWD>RE>Premature Ageing

There actually is quite a bit of evidence of a causal connection between
telomere loss and cell aging and also cell aging and organismal aging.  In
regard to the former, or course, telomeres are lost in mortal cells that lack
telomerase, immortal cells like the reproductive cells, have abundant
telomerase and stable telomeres and when cells immortalize as in cancer they
abnormally acquire telomerase acitivity.  This is correlative evidence. 
Recently, U.T. Southwestern published in EMBO J evidence of causality,
extending the telomereres of cells increased their replicative capacity as you
would predict.  

In regard to evidence that cell senescence is occuring in vivo, the evidence
is seen in many ways.  Cells cultured in primary cultures from old people's
tissues contain many large nondividing cells that have many markers of cell
senescence (morphological, gene tag markers, enzyme markers such as beta gal,
and lastly telomere length)  For instance in the case of skin, dermal
fibroblasts from aged donors turn blue in X-gal as do cells at the Hayflick
limit and telomere length has been shown to shorten in the skin with age. 
When the beta-gal assay was performed on skin sections in situ, blue cells
were shown to be present only in donors over the age of 30 or so, and only a
percentage (probably less that 50%) were seen to show senescent markers even
in very old donors.  But this is what many would expect, that is, that cell
senescence in a minority of cells can have a dominant effect on tissue
metabolism.

Personally, I like to say that no one dies of old age, but rather, we die
because of disease.  But that isn't to say that disease and aging aren't
sometimes the same thing.  If we defined age-related pathology not as the many
pathologies that simply increase in frequency with age, but as pathologies
that virtually everone sees manifestations of in advanced age (such as
atherosclerosis, AMD, osteoporosis, etc, then maybe, these pathologies are
actually the manifestation of aging in that given tissue (i.e. sometimes a
senescent cell may be a "sick" cell.

--------------------------------------
Date: 4/1/96 2:46 PM
From: jpissa at welchlink.welch.jhu.edu
Oliver Bogler <obogler at ucsd.edu> wrote:


>This is all very interesting, but you seem to unaware that there is no
evidence of a 
>connection between telomere length/cellular ageing and organismal ageing.
Organismal 
>ageing is better discussed in terms of mortality - no one dies of "old age".
There is 
>always a "pathology", and that has nothing to do with telomere length.


You are right to point out the shortcomings of the current 'Telomere'
theory of aging. Nevertheless, it is not entirely clear that no one
dies of 'old age'. Autopsy studies indicate that 20-30% of deaths in
the elderly cannot be attributed to a specific pathology. While this
may certainly be due to missed diagnoses, this proportion of 'unclear'
cause of death is higher than that seen in autopsy studies of younger
individuals. I think that the notion of dying of 'old age' i.e.
because of a limited lifespan that is not disease related remains open
for discussion. Any comments anyone ?

Jean-Pierre Issa MD
Johns Hopkins Oncology Center



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To: ageing at net.bio.net
From: jpissa at welchlink.welch.jhu.edu (Jean-Pierre Issa)
Subject: Re: Premature Ageing
Date: Tue, 02 Apr 1996 00:49:28 GMT
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