From: french@RUST.ZSO.DEC.COM
Newsgroups: bionet.molbio.ageing
Subject: The foutain of youth?
Date: 15 Apr 92 01:16:12 GMT
Distribution: bionet


DISCLAIMER:

I am not a biologist or an expert in genetics.  However, I
have studied genetics and DNA replication in some detail
and have come up with an interesting hypothesis on ageing
and possibly a path to the foutain of youth. I present it
here only because there may be some remote possibilty that
it contains some new insights into ageing process.

Much of the hypothesis that follows is based on a little bit
of knowledge and a lot of speculation...

            
HYPOTHESIS:

Ageing can be broken down into several distinct components
that operate concurrently:  

  1. An organism's DNA is programmed to execute a pre-determined
     life-cycle by turning certain sets of genes on and
     off in a pre-determined sequence.  Genes are turned
     on and off through a process that modifies the
     DNA's methylation pattern. 

  2. As ageing occurs, free oxygen radicals and radiation
     cause random errors to be introduced into the DNA's
     methlyation pattern.  The result of such damage is that
     random genes may be turned on or off at the wrong point
     in an organism's life-cycle and thereby disrupt the
     proper cell function.

     Radicals and radiation may also damage an organism's
     DNA by altering the sequence of nucleotides encoded in
     the DNA and thereby introduce random genetic mutations.

  3. Body tissues, that aren't being constantly replaced, tend to
     degrade over time.

A mechanism that negates each component of ageing already exists in
the form of the reproduction process - when an egg is fertilized,
(1) the DNA's methylation pattern is reset to that of an embryo,
(2) errors in the DNA are corrected, and (3) all body tissues are
replaced by growing a new body.

The problem with the reproduction process is that it only works for
germ cells - or does it?  Perhaps reproduction is just one facet of
a DNA error-correction mechanism that is at work in all cells.  When
fertilization occurs, such an error-correction mechanism would remove
differences between the DNA in the parent's germ cells and thus reset
the DNA's state to its embryonic form.  For non-germ cells, that have
differentiated, such an error-correction mechanism would remove most
random errors introduced by radical and radiation damage.

What form would such an error-correction mechanism take?  I imagine it
would be something like a Holliday junction where two DNA duplexes are
merged.  For example, the input to the junction would be two strands of
DNA containing errors and the output would be two error-corrected
strands of DNA (a strand from each parent).

Such an error-correction mechanism would explain how an embryo's
methlyation state gets reset to its embryonic form.  It would also
explain how children start off with an essentially clean slate of
DNA instead of inheriting the bulk of the errors present in their parent's
DNA (most errors are unlikely to occur at the same chromosome site in
both parents and thus can be corrected.)

If such an error-correction mechansim is also at work in non-germ
cells, it might be used to reset an organism's genetic age to an
earlier date (ie foutain of youth).  To do this, you would take a
snapshot of a cell's DNA by duplicating its chromosomes so that
two identical copies of the genetic information exist within the
cell. Errors would then accumulate independently in each copy of the
chromosomes and their information content would slowly diverge.
At a later date, you could reset the genetic age of the cell to the
time the snapshot was taken by running matching copies of the
chromosomes through the error-correction mechanism.  The differences
between the two chromosomes would be removed and their genetic
age would be reset.

To preserve the age of a multi-celled organism, the differentiated
state (methylation pattern) of the DNA in each cell must be preserved.
Thus it would be necessary to generate duplicate copies of each cell's
chromosomes (preserving the DNA from a single body part would not work).

Since, at best, this method can only reset an organism's age to the time
the genetic snapshot was taken, we are all doomed to age gracefully (or
ungracefully as it may be) untill the necessary technology is developed!

P.S. How would one design an experiment to see if a cell's genetic
     age could be reset using the method described above?  Has
     anyone attempted such an experiment?