Defining AGING processes was "Black box"

Steve Chambers steve at chambers.ak.planet.co.nz
Mon Mar 20 21:32:13 EST 1995


In <199503150638.RAA26907 at sol.ccs.deakin.edu.au> drierac at deakin.edu.au 
(Chris driver) writes:

<stuff at end of post>

>If you believe you can come up with a good defination of an ageing process 
>which will encompass these observations, perhaps you should let us know....

OK, I accept the challenge.  This issue of a definition for aging may 
seem to some to be a trivial exercise in semantics.  Not so - it’s 
probably today’s biggest single impediment to progress in aging research.  

Why is there so much disagreement and confusion in aging research?  Much 
of it arises from what most gerontologists BELIEVE about the nature of 
aging rather than what they KNOW.  These beliefs are best summarised by
Bernie Strehler’s (Strehler, 1977) four criteria for defining primary 
aging events.  The oft-quoted criteria are; universality, deleteriousness,
progressiveness and intrinsicality.  

Let’s say this another way and apply it to human beings.  These 
gerontologists believe that for a process to qualify as an aging 
process, it must happen to everybody, it must be progressively damaging,
and it must be a natural part of being human.   

This de-facto definition of aging is a classic example of how 
so-called "truths" can sneak in through science’s back door.  Such a 
definition is consistent with what each of us has experienced in 
ourselves or in others.  It "seems" right, so many scientists have 
accepted it as dogma.  Yet this dogma has never been subjected to the 
rigours of scientific testing and debate.  Good arguments can be made 
against the appropriateness of all four of these criteria.  Let's look
at each in turn.

I've not sighted Strehler's original comments, only various references
to them.  I hope he'll forgive me (and blame the Oxford dictionary) if 
I've misinterpreted them.  

UNIVERSALITY
------------
With few exceptions (see my recent posts - Non-aging species) most people
would agree that aging is universal.  However, most would also agree that
aging is not ONE process but a combination of several.  For the 
purposes of this post I'll take these as given.

It takes no great logic to realise that a combination of processes that 
results in the universal phenomenon we know as aging might conceivably be 
composed of individual processes that are NOT universal.  

There are a vast number of conditions that cripple us in our later years
and ultimately kill us.  Most of these are not universal within species
and they're certainly not universal across species.  Their "universal" 
ultimate effect, however, is some form of (usually) graded decrease
in viability leading to death.

You mention cardiovascular disease and question whether it can properly
be considered as aging.  Let's discuss the subset referred to as
atherosclerosis.  In humans, this process is responsible for many of 
the progressively debilitating conditions we associate with age, and 
it kills.  

Let's say that there are many other processes with these same attributes
Let's say that every human is subject to a large subset of such a group.
Each person will "age" and die, but the nature of that aging and death 
will vary.  Sound familiar?

DELETERIOUSNESS
---------------
This would seem to be beyond debate - but is it?  Just because a 
process can't be shown to be significantly "deleterious" within
the normal lifespan of an organism in its usual environment
doesn't mean it shouldn't be considered an aging process.

Many people believe that examining the in-vitro doubling potential 
of a fibroblast culture is an appropriate study of aging.  Why?  Because
the so-called "Hayflick Limit" has the POTENTIAL to influence the
life-span and viability of an organism.  There is little or no evidence
to show that this phenomenon is deleterious in-vivo - indeed, it seems
that the opposite is the case.

Grey hair is (and should be) generally thought of as a sign of aging.
This, despite the fact that it's not considered "deleterious".  I choose
this trivial example because it also demonstrates the dangers inherent in
using this criterion - carrying plumage that tells a predator that I'm 
a little slower than the rest of the herd can hardly be considered benign.

PROGRESSIVENESS
---------------
Salmon, octopii, annual plants, insects by the truckload - they all 
reproduce and die quickly.  There has been much debate as to whether 
semelparity should properly be considered aging.  I believe it should.

In a multiple process model there is plenty of room for quick-acting
aging processes - provided they have their effect in the latter part of
life.

There's nothing particularly progressive about menopause, or the onset
of presbyopia for that matter.

INTRINSICALITY
--------------
This criterion suggests that any aging process must be largely 
independant of an organism's behaviour and of it's external environment.
If ever there was a reason not to explore the possibility of aging
intervention, this is it.  Why bother?... by definition you can't do
anything about it ;-)

But seriously.  If I sunbathe does my skin not wrinkle?  Do my thymines
not dimer?  Does my connective tissue crosslink for intrinsic biochemical
reasons or because sit on my butt all day?  (I try not to do either of 
these things BTW).


So if this and similar definitions for an aging process won't cut it,
then what will?  I'm not sure, but I offer this as a basis for further
discussion:

  Any common process with potentially degenerative effects in the 
  longer-term.

There are hundreds, probably thousands of processes that fit this
definition - and I believe that aging IS this complex.  Some might find 
this observation disheartening.  They shouldn't - there is every reason 
to suppose that addressing a small number of these processes will result 
in significant progress.  It's just a matter of determining what these 
most important of processes are.  But to find and recognise these 
processes, we may need to let go of our preconceptions about the nature 
of aging.

I know that many a gerontologist reading this will disapprove (vehemently
no doubt) of this definition, but it has one overiding virtue.  It allows 
us to look for solutions to _everything_ that curtails our living and our 
life.  And after all, that's what it's all about it isn't it?

Steve


>>The problem is quite complex..

>If you examine and old animal or person, the deterioration is quite variable. 
>Some cells are quite `old' and some are relatively unscathed. If you follow 
>the course of deterioration of a particular cell type, are you looking at 
>ageing or a specific pathology? If you look at cardiovascular disease in old 
>people are you looking at ageing?

>The problem is made worse by the fact that not all people suffer from CVD or 
>Alzheimer's. Therefore you can argue as some people do, that these are 
>pathologies and not ageing. If you do that you find that you have defined away 
>ageing, because there is nothing left which you can definitely say "this is 
>not a patholgical change".

>Conversely why are some cells still perfectly functional in old tissues. The 
>example par exellence is the ageing brain. Most cells in most people in old 
>age are relatively unimpaired. Why? Cells only mm away may be grossly impaired 
>by Alzheimers or Parkinsonism. Where there is a global deficit in the brain it 
>more commonly is not intrinsic to neurones.

>Nevertheless these observations and questions seem to be one of the rocks on 
>which most theories of ageing founder. I cannot reconcile a free radical model 
>or a telomere model with these observations that have been well known for a 
>long while.

>If you believe you can come up with a good defination of an ageing process 
>which will encompass these observations, perhaps you should let us know....

>Cheers, Chris Driver

-- 
 ________________________ 
(I_lurk,_therefore_I_am!_\ ,,,                    Steve Chambers
                          (o o)   steve at chambers.ak.planet.co.nz
----------------------oOO--(_)--OOo-----------------------------
(c) Steve Chambers.                   1995. All rights reserved. 
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