Cells and Aging

Tom Matthews tmatth at netcom.ca
Fri Mar 5 02:02:12 EST 1999


Thomas Mahoney wrote:
> 
> In article <36DE1347.9B2BE53B at ryley.com>, james at ryley.com says...
> >
> >Tom Matthews wrote:
> >>
> >> Thomas Mahoney wrote:
> 
> >> > The evidence that cellular loss or thinning of cell walls is conducive
> to
> >> > artheriosclerosis, that the majority of cancerous cells have by-passed
> >> > senescence and that much immunological deterioration is the result of
> T-cell
> >> > senescence all suggest that it is late stage cellular development or
> lack
> >> > thereof that contributes the most to systems failures.
> >>
> >> IMO, all three of those premises go far beyond what is proven.
> >> 1. There is no proof that any thinning of cell walls (I assume you mean
> >> arterial walls here) even if conducive to artheriosclerosis is caused by
> >> apoptosis generated by a reduction of telomere length of any cells.
> 
> You are correct that I was indeed referring to arterial and vein walls.  As
> to evidence of the apoptosis being the origin of this thinning I refer you
> to; Bennett MR et al, Circ Res 1998 Apr 6;82(6):704-712 "Cooperative
> interactions between RB and p53 regulate cell proliferation, cell senescence,
> and apoptosis in human vascular smooth muscle cells from atherosclerotic
> plaques."
> 
> If there is evidence of some other cause of this thinning I would be
> interested in seeing it.

While I didn't state it accurately enough (my appologies), my point was
that is very far fetched to think that telomere induced apoptosis is a
major cause of atherslcerosis.

> >> 2. The majority of cancer cells have bypassed senescence because all the
> >> ones that did not are not detected because they have not caused the
> >> symptoms of cancer. Furthermore, this likely has little relevance to
> >> aging since the DNA in those cancer cells was mutated in such a way as
> >> to make them divided more often than others of their kind or again they
> >> would not have gotten to where they needed to by-pass senescence.
> 
> That sounds like a good hypothesis.  Unfortunately I know of no research that
> supports it.  I can, however, cite several studies like; Bryan TM, Reddel RR,
> Eur J Cancer 1997 Apr;33(5):767-73 "Telomere dynamics and telomerase activity
> in in vitro immortalised human cells.", that indicate the cells do not turn
> cancerous until after by-passing senescence and re-activating telomerase.

You only addressed my first suggestion of an alternative to your
conclusion.
The second one is actually the most logical and more powerful. With
respect to your statement above, it asks "then what made those cells
divid so far as to *need* to by-pass senescence?" Normal (undiseasd)
cells do not do that!

> >> 3. Finally, there is only evidence that T-cell senescence *may* be the
> >> cause of immune deterioration in *some* cases (perhaps even likely in
> >> AIDS). To conclude that T-cell senescence many be the cause of *all* or
> >> even *most* immunological deterioration goes far beyond reason.
> 
> Much is neither *all* nor *most*.

But it is a lot more than *may* or *some*!

> Once again, Dr Effros' work is merely
> evidence that senescence plays a role in "functional decrements of the immune
> system".

Again, only in certain, limited, special disease states.
There is *no* evidence that the reduced immunity suffered by normal
aging individuals is caused by telomere shortening of immune cell
progenitors.

> How great a role is yet to be determined.  However, I know of no
> other research that suggests that there is a gradual loss of T-cell
> functioning that would precipitate a decline in the immune system.




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