Re-Visiting a Post by Lou Pagnucco

James james at
Fri Oct 23 00:51:38 EST 1998

> Now, senescent fibroblast produce many times the amount of collagenases
> - possibly the most important family of enzymes responsible for the
> degradation of the extracellular matrix.  Are these senescent fibroblasts
> responsible for some of the features of aging like lax skin, overly permeable
> capillaries, breakdown of the blood-brain-barrier, some arthritic conditions,
> etc.?
> If so, since they can be identified by staining, can they also be targeted
> by smart drugs which have special affinity for these cells and selectively
> toxic to them?  directly toxic, phototoxic, or apotosis inducing ?


> Additionally, even if the remaining cells did progress more rapidly toward
> senescence, due to this increased cellular production, the majority of them
> would initiate apoptosis rather than becoming senescent.  Thus the overall
> effect may very well be improved functioning of the system(s) in which this
> strategy of eliminating senescent cells were employed.

When you say that the cells "can be identified by staining" I
assume that what is meant is b-galactosidase staining.  That is a
useful distinction for visualization, but probably not a very
useful distinction for targeting drugs.  But, obviously
immunotoxins work against cancer, so with some work we may be
able to get them to work against senescent cells. 
b-galactosidase probably isn't the way to go, but we are finding
more and more differences between normal and senescent cells all
the time - eventually we will find one that can be exploited for
this purpose.  

This strikes me as the type of experiment that would be very
difficult to get funded without a lot more evidence that it would
have some benefit.  I think it's one of those things that is
going to remain as speculation for along time because it's tough
line of experimentation to follow, as it can't be reduced to cell
culture, and may not be amenable to study in mice.

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