Cause of aging

Aubrey de Grey ag24 at
Tue Aug 18 07:39:25 EST 1998

Steve Harris wrote:

> Whether old mitochondria are repaired, or just produced anew and free
> of defect at a sufficient pace, is immaterial.  For the cell, it's
> repair either way.  Any process that makes new fresh cell organelles
> counts as "cell repair" in my book. 

All absolutely agreed.  What currently seems likely, though, is that cell
division (ie selection at the intercellular level) is the only way nature
has yet discovered to do this.  I would dearly love to see more work done
on lobsters and very-slowly-if-at-all-senescing lower vertebrates, since
their tissue structure is fairly similar to ours; however, as things stand
it seems much more likely that they achieve control over mitochondrial
damage by perpetuating myogenesis and neurogenesis, ie by getting rid of
the cells that harbour damaged mitochondria, rather than by containing the
damage intracellularly.  (The best evidence for this that I know of is in
amphibians: Gerontology 1994; 40:161-173.)  You saw in my JAAM paper that
I consider replacement of mitochondrially damaged cells to be a plausible
therapy for mitochondrial decline; the main difficulty with it is that
muscle fibres become mitochondrially defunct in short segments, so getting
rid of the whole fibre is inefficient.

Steve also wrote:

> > What about the possibility of a selection process - with defective
> > cells being weeded out?  Non dividing cells can't afford to weed out.
>    That's a real possibility except for one piece of evidence: your
> germ line.  There aren't that many ova to weed out.  Only one (usually)
> is released per cycle, and with sperm around, a reasonable fraction of
> these become babies (10% ?).   Those zygotes have no non-repairable
> damage (aging).  We don't see prematurely aging babies because the
> mitochondria of the ova of the human race have been getting acumulated
> free radical damage for the the last couple of million years.

This is flawed.  The maintenance of mitochondrial integrity in the germ
line is certainly difficult, but there is an extremely powerful selection
process -- ovulation.  I described this briefly in a reply to Lou Pagnucco
on on July 13th.  We only release (in the strict sense
of "make available for fertilisation") one ovum per cycle, but huge numbers
of others are lost at the same time (by mechanisms that are still being
researched): we start with about seven million (see eg Gynecol Endocrinol
1993; 7(4):285-291).

Aubrey de Grey

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