cells counting off in culture

Chris Driver drierac at deakin.edu.au
Fri Jan 13 13:53:47 EST 1995

In reply to Jan Thorup's question about how do cells count? The seminal work 
by Hayflick and Whitehead pointed out that the changes had to be accumulating 
in the DNA. There has been nothing to change that conclusion since then. 

The genes that are mutated or inactivated when a cell is immortalised include 
p53, a gene whose function is now understood to be that of a guardian of the 
cell. It shuts down DNA and much of the protein synthesis in response to DNA 
damage, until the damage is repaired (or in some cases it will initiate 
apoptosis). It seems likely that rb is also commonly lost, which is a gene 
which shows a number of parallels with p53.

The reasonable conclusion is that DNA damage shuts down mortal cells, whereas 
immortal cells continue to divide and become aneuploid as a result.

It is necessary to assume that the rate of DNA damage increases with age, 
apparently exponentially. It was proposed by Vincent Murray that transposable 
elements should replicate during aging and the associated rate of DNA damage 
should increase exponentially. The proposal is hard to test because it is 
necessary to find the active element among a sea of inactive ones. However we 
have a few ideas... 

Chris Driver
Chris Driver, Ph D
School of Biology and Chemistry, Rusden Campus
Deakin University
662 Blackburn Rd
Clayton, VIC, 3168

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