X-Message-Number: 28
From: Kevin Q. Brown
Subject: theories of aging
Date: 10 Oct 1988

While gathering my material on the fate of Denckla's research (see message #27)

I was reminded of several of the major theories of aging and I thought that some
of you would find a brief synopsis interesting.
                                       - Kevin Q. Brown


Major Theories of Aging
Theories of aging fall into two categories, (1) wear-and-tear theories and
(2) programmed aging theories.  The wear-and-tear theories describe aging
as an accumulation of damage and garbage that eventually overwhelms our
ability to function.  The programmed theories propose a clock in our bodies
that controls not only our process of development but also triggers our

The wear-and-tear theories include the (1) garbage glut, (2) cross-linking,
(3) autoimmune, (4) somatic mutation, and (5) free radical theories of aging.
The "gargage glut" theory asserts that the cellular garbage lipofuscin

(a pigmented fatty substance) accumulates in our cells until they choke and die.
The cross-linking theory proposes that unwanted bonds accumulate between large
molecules so that they no longer perform correctly and just accumulate as
garbage.  The autoimmune reaction theory is that the immune system degrades
(through wear-and-tear) so that it no longer correctly recognizes self versus
non-self and then starts attacking one's own body because it incorrectly
thinks it foreign (and therefore an enemy).  The somatic mutation theory
holds that (wear-and-tear) errors in the DNA accumulate so that eventually the
proteins it makes no longer work.  The free radical theory of aging proposes
that highly-reactive atoms or molecules attach to other molecules, turning them
into free radicals, which in turn attack other molecules, and so on, thereby
inactivating a great number of molecules.  Pearson and Shaw's book "Life
Extension" focused on the free radical theory and recommended taking vitamins
and other anti-oxidants to mop up those free radicals and slow down their
rate of damage.

The free radical theory has the advantage that it seems to be able to encompass
the other wear-and-tear theories of aging.  But, even though wear-and-tear
definitely does occur, the patterns of aging that we see do not completely
fit that model.  Lifespans are quite species-specific; rats live just a few
years whereas Galapagos turtles live over a hundred.  The genetic program
is thus an important factor in aging.  Also, the wear-and-tear model cannot
account for the apparent immortality of cultures of cancer cells.  Furthermore,
interventions aimed at reducing the wear-and-tear (such as adding vitamins
and other anti-oxidants to the diet) typically change only the shape of the
mortality curve (so that fewer die at a young age) but do not increase the
maximum life span.  (One exception is Walford's regimen of "underfeeding
without undernutrition", which seems (to me) to stretch the entire development
and aging cycle.  This, however, may be viewed as evidence for a programmed
theory of aging since it effectively just changes the clock rate for the
program rather than showing that no program exists.)

The two major theories for programmed aging are (1) Hayflick's DNA clock
model and (2) Denckla's hormonal brain clock model.  That we would have
some sort of program for aging and death makes sense because:
  "As Sir Peter Medawar points out, a gene that helps the young (who are
  many) but harms the old (who are few) will replicate well and so spread
  through a population.  If enough such genes accumulate, animals become
  programmed to die."  [Ch. 8, Engines of Creation]
Hayflick noticed that cells (other than cancer cells) in culture will divide
only a fixed number of times and then die.  Cancer cells are apparently
genetically altered so that they no longer have this DNA clock.  Denckla
found that by removing the pituitaries of rats, and then replacing some
of the hormones normally secreted by the pituitary, he was able to REVERSE
several major signs of aging in those rats.  He proposed that the pituitary
secretes a substance he calls DECO ("decreasing oxygen consumption" hormone)
and he worked for years toward extracting and purifying it.  One extract was
particularly effective in producing signs of aging in young rats.  But
Denckla's research stopped when his funding ended and he was unable to get
new funding.  Then something strange happened that I do not understand.
According to Albert Rosenfeld in his (highly readable) book Prolongevity II
(1985, Alfred A. Knopf, Inc.):
  " ... he had really put his search for DECO and its inhibitor on hold
  indefinitely - for moral reasons.  The more he thought about the
  potential consequences of placing in the hands of the public the
  ability to achieve perhaps indefinite prolongevity, the more he decided
  that the public - based on his observations of how other major discoveries
  had been handled - was not yet mature enough to deal with it."
(Was Denckla just bitter about not getting funded or what?)

Both Hayflick's and Denckla's theories may be correct; if one clock does not
get you the other will.  (Also, the wear-and-tear theories may be correct, but
incomplete.)  But, of course, once we understand the mechanisms by which we
age, we will also learn how to alter those mechanisms to our advantage.
For more information, a good place to start would be Prolongevity II (cited
above).  (I have several other books, but they are either much older, more
specialized, or not as readable.)  Also, each issue of The Immortalist has a
brief section on theories of aging and a short list of books on life extension
and immortalism.  Maybe some of you have other books that you would like to
recommend.  Also, if my summary skipped your favorite method of aging, be sure
to let me know!
                                       - Kevin Q. Brown

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