Aubrey de Grey Genetics ag24 at mole.bio.cam.ac.uk
Sun Jun 5 11:39:09 EST 1994

In the FAQ, Tim Hughes writes:

> [The fact that senescence is a dominant property
> suggests that DNA damage is not responsible for
> the senescence phenomenon.  If senescent cells had
> lost a function that immortal cells retained,
> then immortality would be dominant.
> It seems unlikely that senescence would be due
> to a gain of function mutation in all senescent
> cells simultaneously.  If immortality were due
> primarily to a gain of function mutation not present in
> senescent cells, again immortality would be
> expected to dominate.  The remaining possibility
> then is that immortality is due to a loss of function,
> and that senescent cells have retained the normal
> genotype.]

I don't see this.  Surely all it takes for damage to be dominant is for
the damaged DNA to be (before being damaged) a negative regulator of a
gene whose expression causes the cell to senesce.  This regulation
could either be by the gene product of the negative regulator, in which
case the dominance of senescence would arise only if dosage were
relevant (ie if one dose of regulator could not suppress two doses of
senescer), or it could be a direct DNA-DNA cis-regulation, eg where the
regulator DNA binds a protein whose attachment inhibits transcription
of the gene immediately downstream (namely the senescer), in which case
a dosage argument is not necessary.

Am I missing something here?

Cheers, Aubrey

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