Hayflick limit for rapid dividing cells (fwd)

Edward Krug kruged at ESSEX.HSC.COLORADO.EDU
Thu Oct 13 19:36:13 EST 1994

This is my first contribution, I hope it works.
Assuming the cell replication score keeper does ultimately prove to be
telomeric length as you suggested, what is the process which resets the
length with every new egg/sperm pairing?  At a Gordon conference on
ageing in 1983 Joan Smith-Sonneborn described the limited number of
doublings paramecium could undergo (somewhere near 200 doublings) without
sexual conjugation before it stopped dividing and died.  If it was
permitted to exchange DNA during sexual conjugation the counter was reset
to 1 again.  Unfortunately, the paramecium had to be visually separated
after each division to prevent conjugation, so it is practically impossible
to get enough material to do any experiments with.  The point is that the
counter can be reset in some systems.  
	I suspect that this processess is quite different from the
release from terminal differentiation seen in some amphibians when they
regenerate amputated limbs.  There are several amphibians which are
capable of limb regeneration at an early age but after undergoing a
thyroid hormone pulse they loose that ability.  The number of doublings
consumed doesn't jump, the cells have just passed a developmental switch. 
There are some major issues in ageing involved with thyroid hormones, but
I will ask for input on this later.
	I currently grow human foreskin fibroblasts in culture as host for
an intracellular parasite.  I find that with high passage numbers the
fibroblasts become poor hosts for the parasite long before there is a
noticable decrease in fibroblasts growth rate.  I study different media
formulations and I have yet to find anything which overcomes sheer passage
	Also, fibroblasts kept in a low serum medium to stop replication
and just stored in stasis also seem to accumulate some indicator of the
passage of time.  They loose some of their maximum replication potential
even though they are not replicating.  The Hayflick number given for cells
assumes rapid division, but non-dividing cells clearly show the effects of
passage of time.  Is this type of senesence different from that produced
by exhaustion of replicative potential?  I don't know.
	Lastly, the Hayflick number for most cells doesn't apply to the
human condition since it is based on rapidly replicating cells, and in
most animal bodies they only rapidly replicating cells are some form of
lining cells or cancers.  
	Oh, I would that it were simple.
Edward C. Krug
Uni. of Colorado Med. Sch.

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