Roslin sheep/genetics/aging questions

Kevin Paul Grant grant at bit.csc.lsu.edu
Tue Mar 4 06:10:47 EST 1997


 
Forgive me if the material below shows a horrible ignorance of
basic biochemistry.  I have no training in the area.
 
 
The genetic material used in the sheep cloning experiments so
recently in the news was taken from cells from adult sheep. The
procedure resulted in what appears to be another, normal sheep. 
This gives rise to some interesting questions:
 
  1. If aging is due to cumulative damage in DNA wouldn't a
     cloning using DNA from the mammeries (the donor site,
     according to the CNN story) of an adult sheep *not*
     result in a normal, healthy clone sheep?
 
  2. Are there cells ("stem" cells?) in a sheep's mammeries
     that are not susceptible to such cumulative damage and
     that were, in fact, used to get the needed DNA for
     these experiments?
 
  3. Perhaps the DNA used *was* age-damaged but something about 
     the cloning process or some natural process that takes    
     place during the development of the fetus reverses the    
     damage?
 
 
Now if I may drift slightly for just a moment, my understanding
is that:
 
  1. The genes in DNA are covered by molecules that can prevent 
     some of them from doing anything.
 
  2. Every cell in the body has the same DNA but that what makes
     the cells different is that each type of cell has its own   
     specific combination of "uncovered" genes that are able to    
     operate.
 
  3. At different times the set of "uncovered" genes in a cell  
     can change.
 
  4. All of this (and a lot more) is what comes under the heading
     of "gene expression" in genetics textbooks.
 
 
Now the following question arises:
 
  Has "naked" (completely lacking in any covering molecules) 
  DNA from a person ever been checked to see if it is the DNA 
  itself that accumulates age-related damage?  Or is it possible
  that it is the stuff that covers the various genes that gets
  damaged and it is the symptoms of *this* damage that are at
  least partially responsible for aging?
 
 
Perhaps the DNA in sex cells (as they exist in normal fertilization)
is completely "uncovered" and some part of the cloning (or fetal
development) process can completely "uncover" covered DNA, removing
the damaged covering material and thus allowing "adult" DNA to be
used for cloning purposes without resulting in a damaged end-product.
 
If any of this is reasonable, then perhaps a lot of what I've seen
bandied about concerning telomere length and DNA damage is not as
critical to the aging process as it would seem and restoring proper
gene-expression would be a more profitable avenue to pursue regarding
anti-aging.  If this is reasonable, is there any material available
about this sort of thing?  Has anyone ever tried such an approach and
if so what were the results? 
 
 
None of what I'm writing is new, I'm sure.  My interest here is more
along the lines of getting the answers to some questions like:
 
  1. What are the stupid mistakes in what I've written?
 
  2. Can anyone give me further information along the lines of  
     what I've written (at least the parts that aren't stupid)?
 
  3. Does the successful use of "adult" DNA in the "Roslin" sheep
     tell us anything about cumulative damage to genetic material
     as a partial explanation of the symptoms of aging?"
 
 
Thanks,
Kevin




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