about the nature article: apotosis

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Thu Dec 16 10:34:26 EST 1999

private wrote:

> I have finally finished the Nature article about p66 ... does this
> article prove that apotosis is something that should be focused on
> as something to be prevented in order to increase life span?

Absolutely not.  Apoptosis is a vital component of many developmental
processes and almost certainly also later in life too, e.g. as a way to
remove pre-cancerous cells before they become properly cancerous.  It's
also likely that cells which have suffered serious oxidative damage
undergo apoptosis, as a way to eliminate that damage from the organism
more reliably than trying to fix the cell.  The life-extending effect
of hindering apoptosis is highly paradoxical, but it may be possible to
explain it by focusing on the fact that these mice only lacked one
particular apoptotic response, namely the last one I mentioned above,
response to oxidative damage.  (This may be a big oversimplification,
but perhaps not too great.)  The model that I get from this is that
cells (both in vitro and in vivo) detect the absence of this option and
up-regulate other anti-oxidant machinery so as to make the apoptotic
response less necessary.  This would extend the mice's lifespan if the
up-regulation were "unnecessarily systemic", i.e. protected cells that
don't use this apoptotic response in the first place as well as ones
that do.  At least, it would do so if those 'unnecessarily protected"
cells are ones whose age-related decline is prominent in determining
lifespan.  I readily concede that this is a convoluted theory: I just
can't think of (nor have I heard) a simpler one that fits all the data.

Aubrey de Grey

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