What is ageing??????

Sydney Shall bafa1 at central.sussex.ac.uk
Tue Jun 15 06:46:30 EST 1993

In response to a previous contribution, someone has asked me (privately)
how one measure ageing except as disease. This is in my view a very
profound question, so I have taken the liberty of publishing my
(private) response, becuase I should like to hear the views of other
people. I am aware that this can be a very controversial discussion.

	The point is very well taken.
This is a major discussion point in the field.  It has never been
proven formally that there is a process of biological ageing in whole animals
independent of, and unrelated to pathology.
     However, having said that, I would point out three bits of evidence
that seems to say that there is such a phenomenon as biological ageing,
which is genetically modulated.
	There exist both natural and induced variants (?mutants) in which
the natural lifespan value is altered. 
	Experimentally induced mutants of this type have been
described in both Drosophila and in C. elegans (a nematode worm).  And
in humans there exists the human genetic disease called Werner's
Syndrome.  This has been quite clearly demonstrated to be due to an
autosomal, recessive allele of a single genetic locus; and in these
patients lifespan is approximately halved. In addition, there are a
number of other human genetic progeroid (premature ageing) syndromes.
	Thirdly, there is a weak correlation between ageing of cells in
vitro, and human lifespan.  More convincingly, Rohme has established that
there is a very good correlation between in vitro lifespan and either
the mean or maximum lifespans of a wide range of animal species.  This
almost certainly is genetically modulated because Pereira-Smith and
Smith at Houston have unequivocally shown that in vitro lifespan of
human fibroblasts is dependent on four genetic complementation groups.
	These bits of evidence seem very compelling to the notion that
there there is a genetically influenced phenotype of biological ageing,
independent of pathology and damage and accident.  Of course, this
evidence DOES NOT say that pathologym, damage and accident do not cause
morbidity and mortlaity; it is clear that they do.  But it seems that
there are also genetic elemnets that are relevant.
	The definition of ageing therefore, is probably best given for
whole animal organisms as the increasing loss of physiological function
that leads to morbidity and mortality; this loss of function is brought
about by an interacting set of exogenous and endogenous circumstances
and properties. Complex - YES! Vague - very!!!! But I think both helpful
and correct. it provides a framework for investigation; this framework
says that one needs to look to exogenous and endogenous causes of
disease as well as to endogenous explanations for loss of physiological
function with time.
	I hope this stimulates some alternative interpretations!
	Sydney Shall.



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

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