New thinking about the evolutionary nature of biological
aging will profoundly affect medical research on age-related diseases – here’s
why.
Before Darwin nobody thought that the origin of lifespan
was different from that of all of a species’ other traits. Whatever caused a
rat to have a long tail and beady eyes also caused it to have a particular
lifespan, which, like tails and eyes varied a lot between different species. Mammal lifespans vary from less than a year
for some mice to more than 200 years for some whales.
In 1859 Darwin’s survival-of-the-fittest concept changed
that idea. Now organisms were evolving
myriad traits that each caused them to live longer and/or breed more. Because living longer and breeding more was
indefinitely better, organisms were presumably evolving toward immortality. By the present, after billions of years of
evolving longer lives, why weren’t organisms immortal or at least all similarly
limited by some universal and fundamental law of physics or chemistry? Why would lifespans vary so much among even
biochemically similar organisms? Contemporaries
actually wrote Darwin and asked this question!
Biotheorists have been laboring ever since to develop a theory that fits
with evolution theory and simultaneously matches empirical evidence such as the
lifespan observations.
Most gerontologists and medical researchers now believe
one of two main aging theory concepts that eventually resulted: Programmed aging theories, first proposed in
1882, say that species generally possess a lifespan
regulation mechanism that purposely limits lifespan to a species-specific
value in order to obtain an evolutionary benefit.
Non-programmed theories proposed that each species only has
an evolutionary need to live to a particular lifespan and therefore only
evolved the ability to overcome natural deteriorative processes to the extent necessary
to live to that age. Both concepts
explain why species have such different lifespans; both require modifications
to the survival-of-the-fittest idea that we all learned in high school biology
class.
Modern non-programmed theories are based on an idea by
Nobel-laureate Peter Medawar who proposed in 1952 that beyond a certain
species-specific age there is no further evolutionary benefit to living or
reproducing longer. In effect,
survival-of-the-fittest only applies to young organisms where “young” is
defined relative to the age at which the organism is first able to reproduce. Nature doesn’t care what happens to old
organisms. Death and deterioration are
not an evolutionary disadvantage unless they occur before the critical age.
For most people who paid any attention in biology class,
programmed aging, the idea that we possess a sort of suicide mechanism that
purposely pro-actively limits lifespan, appears to be even more patently
ridiculous and more obviously incompatible with the whole survival-of-the-fittest idea than modern non-programmed aging
theory. Indeed, as late as 2002 some prominent
biologists were still writing that programmed aging in mammals was literally theoretically
impossible. Consequently, steadily
increasing evidence of programmed aging such as genes that cause aging was largely ignored by medical researchers.
“Impossible” trumps any amount of evidence.
Meanwhile, beginning
in the 1960’s a number of other theorists were working on trying to explain
some other apparent conflicts between
observations and evolution theory. Darwin’s
theory says that every individual
animal is fighting for the survival
of itself, its mate, and direct descendants and against competitors from its own species. An individual surviving longer and breeding
more produced more descendants having its individual design than competitors
and thus better propagated its individual traits. This is the “individual benefit clause” or
the “dog eat dog” aspect of Darwinian evolution theory. There was very wide agreement that
deterioration and death caused by aging did not represent any evolutionary
benefit from the point of view of an individual mammal!
However, In addition to all of the human societal rules,
laws, and commandments that limit individuals in favor of wider benefit,
theorists observed animal behaviors (altruism)
in which animals similarly behaved in a way that was counter to their
individual best interest, apparently to obtain a wider “group” survival benefit.
A number of other apparent discrepancies
with the individual benefit clause surfaced. Eventually a number of theories
appeared to the effect that benefit to the survival of groups or kin, benefit
to the propagation of genes (the selfish gene theory), or benefit to the
evolution process itself (evolvability theory) could offset some degree of
individual disadvantage and result in evolution of an individually-adverse (or
neutral per Medawar) trait like programmed mammal aging. Multiple programmed aging theories then
appeared based on non-individual benefit resulting from a limited
lifespan. According to these theories,
beyond a species-specific age (also associated with reproductive maturity)
there is an evolutionary disadvantage
from living longer. As only one very
simple example, a longer lifespan in many mammal species would lead to
decreased genetic diversity. A single long-lived
male “king of the hill” might mate with many generations of his own
descendants!
Genetics discoveries, some quite recent, exposed
additional issues with traditional individual-benefit-only evolutionary
mechanics theory. At least two
assumptions made by Darwin and critical to the individual/ non-individual issue
are now provably false. The emerging
reality: the evolution process, rather
than being simple and elegant is actually complicated and messy. The reader may have noticed that the two main
theories are much closer to each other than to traditional evolution theory.
The argument is over whether beyond the critical age aging creates zero net
evolutionary disadvantage (and therefore species never evolved a longer
lifespan) or whether, beyond the critical age limiting survival creates at
least a small advantage (and therefore species evolved suicide mechanisms). Arguing about the difference between zero and
slightly less than zero is a lot like arguing about how many angels can fit on
the head of a pin!
It is now increasingly obvious that programmed mammal
aging is the right theory. Programmed
aging theories now exist proposing that a panoply of wider evolutionary benefits
would result from programmed lifespan limitations. A number of senior advocates of non-programmed
aging have even conceded the validity of the non-individual-benefit
evolutionary concepts that are necessary to support programmed mammal aging.
This essentially concedes the validity of programmed aging because programmed
aging provides a much better fit to experimental evidence.
Why
is this development so important? Programmed and non-programmed theories
predict very different mechanisms behind the aging process and therefore behind
massively age-related diseases like cancer and heart disease. Following the wrong theory is therefore likely
to substantially delay development of ways to treat or prevent the age-related
diseases that in developed countries are now the main cause of death for people over 40! For example, non-programmed theories suggest
that the various manifestations of aging are functionally independent of each
other and that therefore treatments and prevention techniques must be
individually developed for each condition. Programmed theories suggest that, in addition,
there is substantial potentially treatable commonality between various
manifestations, i.e. the program. If
aging is at least partially controlled by a program similar to the one that
controls reproductive functions, we would expect the existence of a “biological
clock” that could be medically altered. We
would expect the existence of signals such as hormones used to coordinate the
activities of various tissues in performing the aging function that could also
be altered.
Researchers following non-programmed theories talk about
preventing or contravening damage, usually associated with a particular
disease. Followers of programmed
theories talk about signals, receptors, interrupting the aging program, and
simulating some effect known to delay aging such as caloric restriction or
exercise in order to “fool” the aging program.
Most of us have been trained from an early age to believe
that the evolution process resulted in the development of all of the
“beneficial” characteristics of an organism but that all of the “adverse”
aspects came from random deteriorative processes or external forces. It is indeed a giant leap to think that
aspects like muscle weakness, sensory and mental deterioration, heart disease,
cancer, increased susceptibility to infectious diseases, arthritis, and other
manifestations of aging are also “beneficial” as seen from the evolution
process point of view and therefore ultimately result from the operation of
complex evolved mechanisms similar to those that produce the traditionally
“beneficial” organism features. However
unless we make this leap we will never really understand aging or age-related
diseases.
More recent posts on aging can be found on Aging Theories Discussions.
References:
Goldsmith TC. The Evolution of Aging 3rd Ed. Azinet Press Annapolis ISBN 0978870905 2012
also Amazon, B&N, etc.
Goldsmith TC. Arguments against non-programmed aging theories.
Biochemistry (Moscow) DOI:10.1134/S0006297913090022 78:9 971 2013
Medawar PB. An unsolved problem of biology. HK Lewis London 1952
Weismann A. Urber die dauer des lebens. Fischer Jena 1882
