"Programmed" .vs. cumulative damage causes of cell-cycle failure

Oliver Bogler obogler at ucsd.edu
Fri Nov 10 14:55:32 EST 1995

In article <30A38FE7.1CFB at evolving.com>, Gregory Bloom <gjb at evolving.com> wrote:

> It appears to me that owing to the continued success of immortalized
> cell lines in dividing and thriving in spite of the usual environmental
> assults from OH- radicals, glycolization, methylation, etc., the
> question of "programmed" .vs. cumulative cell damage as the primary
> cause of ageing swings heavily in favor of the "programmed" causes.

Dear Gregory,
It appears that some confusion between cellular and organismal ageing has
crept in. 

Cellular ageing is, we agree, programmed in the sense that it could be
prevented by nature, but isn't. In other words, cells can be immortal.
What that means is that a clone of cells is immortal, not any individual
cell.If you start by placing a mortal cell in a culture dish, it will
divide for a few cycles (in the 10's) and then spontaneously all the cells
that you have in your dish stop dividing. Note that they don't necessarily
die.(see below). If you do the same with an immortal cell (say one from a
cancer), it will just keep dividing for as long as people have cared to
try. Note that either mortal or immortal cells can be damaged, killed etc.
by environmental conditions. Another good example of immortal cells are
germ cells (sperm and egg mother cells etc.). They are an unbroken line of
cells from you or me to the first organism that was! That is not to say
that some of the cells in that "clone" don't die, but nevertheless the
line is unbroken. These cells all suffer damage, but they can obviously
repair it efficiently. 

Organismal ageing is a different thing (excluding shortlived animals with
suicide mechanisms built into them). Animals consist largely of mortal
cells, which are renewed slowly from pools of stem cells (that may be
immortal, or at least have a long life span). Nevertheless the animal
ages, in part because in many tissues cell renewal is limited, for example
the brain. Damage is accumulated slowly, and also as a result of the
environment. So, although most cells are mortal in the cellular sense
(they stop dividing soon after birth) they can live for over 100 years in
humans. So by maintaining the health of cells that are mortal is
beneficial to the organism. So don't throw out those vitamins.

The question of cellular immortality is also closely linked to cancer.
Cancerous cells are immortal and it is usually the case that making cells
immortal in that sense increases the chance that they become cancerous.
What we need is cells that are mortal (don't divide) but can function for
ever, if we want to be immortal. Such functional immortality may be
impossible to achieve on its own, because it may well turn out that
cellular immortality is inextricably linked to cell division.

Oliver Bogler
obogler at ucsd.edu

Oliver Bogler
Ludwig Institute for Cancer Research, San Diego Branch
obogler at ucsd.edu

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