Phil Chapman wrote:
>> On Tue, 10 Mar 1998, smc wrote:
>> > On Mon, 09 Mar 1998 22:04:33 -0600, Iuval Clejan <spring at jumpnet.com> wrote:
> >
> > Regarding C. elegans, I'm pretty certain all its cells are post-mitotic
> > and so are not replaced. However, CE still ages and dies, as do all
> > post-mitotic cells (e.g. neurons), and so this is where the involvement
> > of telomeres and telomerase in ageing becomes uncertain.
>> It is this accumulation of rDNA circles which is the researchers think is
> the cause of ageing, at least in yeast. Extrachromosomal rDNA circles
> (ERCs) are formed by excessive homologous recombination. It is thought
> that the SGS1 gene product repressed the formation of these, although
> exactly how it does it is unknown.
The problem raised by smc still remains for the ERCs:why do post mitotic (G0) cells age?
ERCs can only accumulate during S phase of mitotic cell cycle or during meiosis , and
adult C. elegans cells undergo neither of these. Maybe the adult C. elegans cells that
age already have a number of ERCs and these cause errors in rDNA transcription. This has
a positive feedback effect, since ribosomal RNA is needed for making more ribosomal RNA.
And the DNA repair enzymes can't keep up with an exponentially growing defective rRNA.
And once rRNA is no good, no proteins of any kind can get made.
More hypotheses: what if the genes coding for DNA repair enzymes are near the start of
the telomeres, and if the telomeres get short enough, these genes start getting damaged?
Again a positive feedback effect: the repair machinery gets damaged, which means less
repair of it. And once the repair enzymes are no good, mutations accumulate
>
>> If your interest has been raised by what I've written, read the article in
> Cell entitled 'rDNA Circles - A cause of ageing in yeast?'. I can't
> remember the exact reference but it should be pretty easy to find.
> D. Sinclair and Ponce de Leon (aka L. Guarente) Cell v91, 1033-1042, Dec. 26 1997
> I look forward to some interesting discussion on this point.
As do I. Please continue to point out obvious fallacies in my arguments, as they are
based on a weak foundation in molecular cell biology (I'm a physicist, and most of the
biology I know is self taught)
