How do we age?

Sydney Shall bafa1 at uk.ac.sussex.central
Fri Sep 17 06:18:33 EST 1993

Gail Murray asked today how is it that we age, if our cells are replaced very frequently.  In fact, our cells are sometimes replaced much more frequently
than every several years; skin cells are replaced in days and weeks, and cells
in the gut are replaced every few days.

Jim Cummins responded to the query from Gail Murray by saying that ageing
ONLY (my emphasis) occurs in post-mitotic tissues, that is tissues in 
which the cells have stopped dividing.  This is only partially true.
The ageing of post-mitotic tissues such as neuronal (brain) cells and muscle
cells is very important, but there is also ageing in other tissues in
which there is cell division; so how do we explain this type of ageing.

I propose (following the original idea from George Martin of Seattle) that it
is the using up of the proliferative potential which we have in most of our
bodies that prevents adequate regeneration of damaged cells in any given tissue.
Thus in older people, I suppose that their tissues cannot maintain themselves
adequately, because the cells cannot raplace damaged cells efficiently.

This idea is very well supported by the human genetic disease called
Werner's Syndrome, in which people age prematurely in a very dramatic
fashion.  In this disease there is no fast ageing in the non-dividing
tissue, only in some of the dividing tissue.  This disease therefore
demonstrates that there is a form of premature ageing, and therefore presumably,
a form also of normal ageing that only affects certain dividing tissues.

The details of the loss of ability to divide in this condition have recently
been worked out.  The disease is also interesting because we know that it is
caused by ONE single mendelian locus on one of the non-sex chromosomes.
Attempts are being made to identify the relevant gene and to isolate it
to see how it works.



Sydney SHALL,
Laboratory of Cell and Molecular Biology,
Biology Building,
University of Sussex,
East Sussex BN1 9QG,

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