Ageing and methylation

mjfasmb mjfasmb at fs1.ce.umist.ac.uk
Fri Apr 11 05:53:24 EST 1997


> > Jean-Pierre Issa wrote :
> > I disagree with your dismissal of methylation's role in
> > aging: DNA methylation patterns are reset during early
> > embryogenesis. In fact, the Dolly experiment supports a
> > methylation theory of aging (changes irreversible in adult
> > cells but reversible in embryonal cells) over a mutational
> > theory of aging (changes irreversible no matter what).
> > Incidentally, there is some data suggesting that this may be
> > true for some cancers as well.

I'd agree that the mutational theory (by itself) is a very 
weak argument for ageing.   However, oxidative damage has been shown 
to play a central role in the ageing of post-mitotic tissue and can 
reduce the replicative lifespan of mitotic cells.
As for methylation - the question is whether changes in the 
methylation state of DNA occur as a consequence of ageing or actually 
cause the phenomenon.  If such changes merely reflect altered 
expression patterns (?) you would expect to see them in embryonic and 
cancerous cell lines anyway.

An added complexity is that there are different types of cellular 
ageing : clonal senescence (as exhibited by most mammalian cell 
lines), where mother and daughter inherit approx. the same age; 
asymmetric senescence (as exhibited by yeast), where the daughter 
cells age is usually reset to zero and finally temporal senescence 
(as occurs in post-mitotic tissue).  Most people refer to `immortal' 
cancer cell lines - reflecting the loss of clonal senescence and the 
ability to propagate the cell line indefinitely.  However i very much 
doubt whether cancer cells are truly immortal - I'd be willing to bet 
a months salary that such cells have merely learned to behave like 
their distant yeast-like ancestors and now perform asymmetric 
senescence.
The resetting of age at embryogenesis and what occurs during 
`immortalisation' of a cancer cell line are two very different 
things.

MGB
X





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