Must an AGING PROCESS be universal? was Defining...

Andrew K. Groves grovesa at starbase1.caltech.edu
Wed Mar 29 13:45:40 EST 1995


In article <Pine.SOL.3.91.950328223136.772B-100000 at corona>, Patrick O'Neil
<patrick at corona> wrote:

> On Tue, 28 Mar 1995, Oliver Bogler wrote:
> 
> > When considering ageing as a process of cells, rather than organisms, then
> > it is clear that some cells, such as bacteria, or parts of organisms,
> > don't age. The germline is an unbroken lineage going back to the origin of
> > life, 
> 
> Even bacteria, in the strictest sense, cannot be considered immortal.  
> They have to actively and constantly replicate or die.  The daughter 
> cells, due to the inherent error rate of DNA polymerases, ensures that 
> none are the exact replica of the progenitor.  If you were to do the 
> equivalent, you would be a big lump of ever-dividing cancer.  
>

You are assuming that immortal cells are 'cancerous'. This is not the
case. Immortal cells have pretty much the same limits on proliferation
that normal cells have. It is true however, that continuous propagation of
immortal cells may lead to some cells picking up mutations and becoming
transformed.


> Quiescent cells are not immune to damage, which is inevitable, so they 
> do, in fact age.  In the very least, if you wish to dispense with the 
> idea of aging in these particular cases, then just existing for a period 
> of time demands that damage will occur for which the cell cannot 
> recover.  Eventually, then, such cells will die and it will be FAR sooner 
> than 200 years.
> 
> The germline is not itself an unbroken replicative chain.  Since 
> replication in the process of meiosis is occuring at a high rate in 
> germline cells, errors are also occuring.  No sperm or egg is going to 
> carry the exact same DNA makeup as the parent.  Hell, it is unlikely that 
> you could find two cells in your body within which the base sequences 
> are absolutely identical.  With the size of our genomes coupled to the 
> normal mutation rate of replication, you are certain to have at least one 
> erroneous base incorporation in each cycle.  
>  
> You can, perhaps, decrease the natural error rate to below 10^-10 or 
> 10^-11 per basepair per replication cycle, but you cannot prevent error 
> entirely, so time-related deleterious mutations are inevitable.  Call 
> THAT aging if you wish.
> 

You seem to be saying that any damage to DNA constitutes or contributes to
"aging". It's not clear to me why this should necessarily be so. I would
suggest that Oliver and yourself are talking about two different things.
He is considering the capacity of a cell for division. It is clear that
some cells in eukaryotes retain proliferative capacity, and that other
cells have a restriction on the number of divisions they can undergo
before becoming senescent. (Note the difference between senescent, which
is pretty much final and irreversible, and quiescent, which means that the
cell in question is not actively dividing, but retains proliferative
capacity). You are relating aging to DNA damage. I would suggest that what
you are talking about is one cause of molecular evolution, rather than
aging.

Just my $0.02

Andy

-- 
Andy Groves
Division of Biology, 216-76
California Institute of Technology




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