aging questions

JULIO KARWOSKI xman4321 at themall.net
Thu Mar 6 02:32:38 EST 1997


John Josephson wrote:
> 
> > ... .
> > I want to suggest that DNA methylation holds some answers to your
> > questions.
> > Although I don't know much about it, as far as I know, DNA methylation
> > patterns change as a cell differentiates, or ages.
> > Perhaps DNA methylation appeares to be involved in transcription
> > regulation. I remember the journal Cell has several good reviews on it.
> > I hope that this discussion goes on.
> > Is there anyboy to comment it? I am really excited by this great post.
> >
> > Best regards
> > Hang-Jun Jang
> 
> Richard Cutler has proposed what he calls the "disdifferentiation
> hypothesis," basically, that a big cause of the disfunctions of aging
> may be that differentiated cells tend to loose their specificity over
> time so that, for example, neurons tend to make more muscle proteins,
> livers make more skin proteins, etc.  That they do so is supposedly an
> experimental fact; what is in question is whether that is indeed a deep
> cause of the manifestations of aging, or whether it is more an effect
> than a cause.  (Sorry, I can't give references right now.)  Presumably,
> too, one main way that the differentiation of cells is maintained is by
> methylation of DNA.  (Though I think that methylation is supposedly used
> to do some imprinting across generations, i.e., for some genes it matter
> whether you got the gene from your mother or father, and that the
> mechanism for this sex imprinting is methylation of DNA. So perhaps just
> putting the nucleus of an adult cell into an egg is not enough to remove
> all methylation.)
> 
>  .. jj

Hello Mr. J.J. and Mr Han Juang:

I was somewhat surprised and pleased that somebody brought the methylation 
hypothesis to explain the cloning process. From what I read, these British 
researchers had to fertilize about 300 cells to obtain one successful 
fertilization. It appears that the DNA of the unsuccessful attempts was 
damaged in some way. Methylation is one of the major mechanisms for gene 
silencing and I am surprised that it is given so little publicity by those
involved in aging research. The genetic "imprinting" as Mr J.J. well points
out is according to some researchers an inherited pattern of distribution 
of methyl groups along the DNA strand. In addition to maintaining the 
expression or silencing of the appropriate genes, there is a loss of methyl 
groups with each cell division, and also due to random damage in 
postmitotic cells. This loss of methyl groups {C-H3} will cause some 
unwanted genes to be expressed, and according to several authorities will 
cause the appearance of scenesence. To me this theory is quite conclusive.
There could be still a more basic mecanism for cellular aging but these 
researchers are definitely on the right track. The books I would recommend
for anyone to read on the cutting edge on aging research are:

               genes and aging, by M.S. Kanungo
               understanding ageing, by Robin Holliday

They give a comprehensive review of the different theories and focus an 
what is the most logical cause of aging at the cellular level, the inherent 
failure of maintenance mechanisms of the cell. For example, methylase does 
not repair the missing methyl groups perfectly, therefore, eventually the 
cell will have unwanted active genes. J.R.Smith from the University of 
Texas has, without mentioning methylation as a cause, discovered that 
unwanted proteins are expressed in aging cells. He has identified these 
proteins and his results have been confirmed by a different route by 
other researchers. They only focussed their research on those proteins
which interfered with cell division. Their studies were done by cell fusion
techniques. If anybody is interested in more information or the articles 
I have, please post. J.R. Smith also has a home page with useful information.

cordially,
               Julio Karwoski




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