X-Message-Number: 9357
From: (Steven B. Harris)
Newsgroups: sci.life-extension,sci.med,sci.cryonics
Subject: Re: Evolution of aging (was Insulin Resistance and CR)
Date: 26 Mar 1998 03:32:56 GMT
Message-ID: <6fci98$>
References: <6f9j99$1me$> <6fa8mo$>

>In <6f9j99$1me$> Zooko Journeyman 
< writes: 

>Thanks to the several contributors for informed discussion of 
>the evolution of aging.
>
>Do i understand correctly that the current scientific consensus
>is that aging has little enough of a(n extended) phenotypic 
>effect upon other organisms that it can be considered 
>evolutionarily neutral? 

Comment (edited a bit for typos):


   That depends on what you consider "aging."  In times past, the
time-dependent part of the Gompertz-Makeham curve was considered
aging, and that term takes care of 90% of deaths in low Makeham-
term conditions (i.e., in low accidental mortality conditions,
such as populations in zoos, or populations getting good medical
care in industrialized countries).  If this early time-dependent
exponential mortality is "aging," then "aging" is probably caused
by genetics (antagonistic pleiotropy from genes important in
youth but causing problems in old age) coupled with the effects of
stochastic (random) catastrophic failures which result from these. 
Examples are cancer promotion and initiation.  Or fractures from
osteoporosis caused by bone loss at low estrogen levels (great for
lactation, not so good for granny).  Or emboli and infarctions caused
by a clotting system which works well at young ages, but not later.

    Obviously, however, looking at real mortality curves shows
that they are not quite Gompertzian.  If you look at the rise in
mortality, it is exponential up to a point, and then something
happens.  There is, in short, more than one "aging processes," if
the mortality curve suffers an extra inflection after 90% of
animals have died after good conditions, and now the time 
dependent force of mortality begins to wain.  Which *is* what
happens in real mortality curves in everything from humans to
rats to fruitflies.  What, you say--- aging slows down?  A better
guess is that "aging" has always been there since puberty,
increasing chance of mortality slowly and perhaps linearly, but
has until very late in life (90% of max lifespan) been covered up
by late (and bad) effects of various other physiologic processes,
which are designed to make us work better then young, but which
become a hinderment (and exponentially risking source of 
mortality risk) when we become old.  

   Perhaps this non-exponential aging process, the one that kills
the last 10% of animals in any population, and is characterized
by simple dropout and death and fibrosis of cells in all organs
(with attendant linearly increasing organ dysfunction), has been
going on for all of the lifetime, and is a better candidate for
"true" aging.  After all, some lucky people escape the premature
death from pleiotropy problems (Jean Calmette), but nobody
escapes this latter process.  And aging is nothing if not
universal. 


> (Where the sloppy maintenance 
>hypothesis considers aging as such evolutionarily neutral, but
>maintenance as evolutionarily significant.)

   Yes, this last kind of aging (outlined in Kirkwood's 
"disposable soma" theory, 1977) has more to do with the cost of
maintenance, because it results in sloppy maintenance where good
maintenance is not needed, due to expected short mortalities from
the prospect of being lunch, rather than the prospect of immorta-
lity.  But sloppy maintenance in an animal of course does not
show up in just in one place-- rather it shows up everywhere at
roughly the same rate (why run maintenance better in one place
than another-- that's just wasted energy.  Good engineering never
builds any part too much stronger than the others).  That is why
people who die after the age of 100, typically die with 
everything wrong with them, but nothing in particular. 

    In other words, you can look at a typical lifespan curve and
guess that both major aging theories postulated in this half of
the 20th century are true.  It's the case of the seven blind men
from Hindustan (Sach's poem), and all are right.  The 
antagonistic pleiotropy theory of Medawar explains time-dependent
(exponential) increases in mortality during the first 90% of the
way to maximum life span, ala Gompertz.  But that's not all there
is to explain about mortality changes with time (though some
texts simply DO ignore the mortality curve tail).

   If you escape the bad geriatric effects all those genes that
help you in youth, but hurt later (those that cause dessert
cravings, fast clot making, and so on), then the deaths of your
last 10% of your population sample, with its much gentler
increases in  force of mortality over time, are non-Gompertzian
mortality, and are explained better by plain old wear and tear. 
Death here is stochastic, and results from random perturbations
of a system which has become fragile in all parts, due to bad
upkeep.  The evolutionary rate of upkeep is amenable to 
evolutionary forces.   If predation and stochastic mortality are
low enough, and energy cost of upkeep is low enough, that it's
worth the while in reproductive and repair costs to delay wear
and tear, when the organism can.  But even here there are
apparently limits, as we know of no designs built around perfect
or near perfect repair in nature's designs for animals with
working brains or muscles.  Or alveoli or glomeruli. Nature is
profligate at building one-shot devices which give creatures
short term advantages, but can't be fixed any more than that
factory-sealed electronic-timing box in the new cars.  

   What this means is that you can have agelessness if you don't
mind being a huckleberry or coral polyp or hydra.  But what kind
of a deal is that? For the rest of us, nature can perhaps give
you a slowdown in aging, and an increase in metabolic time of 2
or even 5, if you have a big brain, or wings, or a shell.  if you
need more than that, you'll have to hope that cryonics and
nanotechnology succeed.

                            Steve Harris, M.D.

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