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
AUSTRALIA
