Aubrey's "survival of the slowest" hypothesis

Iuval clejan clejan at mindspring.com
Tue May 8 13:30:53 EST 2001

Aubrey de Grey wrote:

> Iuval Clejan wrote:
> > what do you think of Wallace's PNAS 98 (Feb 2001) paper about the Sod2
> > (+/-) mice? I have only had time to read the abstract and conclusions,
> > but it looks like he makes a case for even 1 mito having sufficiently
> > defective membrane as likely to cause apoptosis before being
> > phagocytized by a lysosome. Seems like an inefficient strategy. Perhaps
> > it depends on the type of cell: if in a proliferating cell then maybe
> > apoptosis is more efficient, while if in a non proliferating cell
> > lysosomal ingestion is more efficient.

I meant not "type of cell" but "type of neighboring cells" etc.

> It's not clear how many mitochondria need to undergo the permeability
> transition in order to tip a cell into apoptosis.  I don't know what
> you're interpreting as that number being one.

You're right, it is unwarranted to deduce that one mito undergoing PT induces

Is the decrease in both mitochondial and cytosol lipid peroxidation he finds
in MnSOD(+/-) mice in going from middle to old age consistent with RHH? It
seems not. According to RHH, although mt lipid peroxidation should decrease
with age for rare cells (those that have been taken over by respiratorily
defective mutants), most other cells will exhibit increasing lipid
peroxidation both in their mitochondria (where mutants haven't occured yet)
and cytosol (due to oxidative species which keep increasing fundamentally due
to the defective cells). The hypothesis that apoptosis removes cells with
enough defective mitochondria explains this phenomenon.

Perhaps this could be an extension to the RHH, since both phenomena could be
occuring simultaneously, with the ratios determined by the cellular
environment, as I mentioned before.


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