> Senescent cells beside being blocked from replicating also adhere less
> rigorously to their differentiated phenotype, produce more free radicals than
> non senescent cells and show signs of inappropriate genetic expression. An
> example of the latter is in senescent fibroblast that produce many times the
> amount of collagenases than non-senescent fibroblasts.
I think that we need to distinguish quite carefully here. While the
behavior that you have described above is *correlated* with
non-replicative cell capacity, ie senescence, it may not at all be
*caused* by senescence. In my view it is more likely, that both
senescence and the various behaviors which you have described (and many
more possibilites) are both simply caused by the *aging* (time passage)
of cells. It would be an interesting experiment to see whether slow
dividing cells which have reached senescence because of telomere
reduction, display more of these aging attributes that do fast dividing
> Each of these processes are detrimental to the cellular tissues involved and
> likely to the functioning of the organ system in which they are located. By
> avoiding apoptosis these senescent cells may block the production of more
> functional cells as has been proposed for T cells in the immune system. By
> expressing a more embryonic phenotype the cells may not function properly for
> the organ system in which they are located and the increased production of
> free radicals may damage the cell, causing further deterioration of its
Two things here.
1. In this case apoptosis would be beneficial whereas above you talked
about it being part of the problems of aging. Thus, you need to be very
careful about the "place" and relevance of apoptosis to the Telomeric
theory of aging.
2. While senescent cells are, in general, less differentiated, I think
this is simple related to changes which have taken place during the time
of aging (reversal of inhibited gene expression). I believe it is quite
wrong to refer to this in any manner as a kind of reversion to
"embryonic phenotype". It is more of a pure and simple, uncontrolled
*distortion* of their natural differentiated phenotype. Still, as you
say, the result is that they contribute inefficiently or even harmfully
to their parent tissue.
> Finally inappropriate genetic expressions can disrupt the production of
> necessary bio-chemicals like cd 28 required for telomerase activity in T
> cells or the production of inappropriate bio-chemicals like collagenase in
> fibroblasts, that can not only damage the cell itself but also the matrix
> surrounding it and nearby cells.
>> Telomeric shortening leading to cellular senescence may be the primary factor
> in how replicative cellular systems deteriorate over time and lead to
> organismic death.
I think you conclusion is inappropriate unless/until you show that
telomeric shortening *causes* the inefficient and destructive aging
attributes of cells, rather then simply being correlated with them. This
is seen by simply imagining that telomeres do not shorten and cells do
not senesce, but simply accumulate all the other aging attributes over
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