Aging Theory
Questions and Answers
Theodore C. Goldsmith
This set of questions
and answers concerning biological aging theories is a companion document for the book:
Introduction to Biological Aging Theory.
What is biological aging (senescence)?
Senescence refers to the internally-caused gradual
deterioration and eventual death seen in mammals and most animals.
What is meant by lifespan?
Average lifespan refers to the
average time an individual member of a species could be expected to live in the
absence of any external limitations on lifetime such as predators, infectious diseases, food supply, or habitat
availability. Maximum lifespan is the maximum observed lifespan for a species,
such as under zoo conditions. Mammal lifespans vary over a range of more than
200:1.
What is an age-related disease?
An
age-related disease or condition is one in which incidence and severity
drastically increase with age such as cancer, heart disease, stroke, Alzheimer’s
disease, cataracts, hearing loss, etc. These diseases have many different causes
and different treatments directed at those causes have been developed and
applied. Age-related diseases and conditions are similar between mammal species
but occur on vastly different age schedules. Aging theories attempt to explain
these observations.
What is an evolutionary mechanics theory?
An evolutionary mechanics theory attempts to describe the
evolution process, the “how it works” aspect of evolution.
What is Darwin’s survival-of-the-fittest or natural selection evolutionary
mechanics theory?
Darwin suggested in 1859 that the
evolution process caused organisms to acquire evolved inheritable design
characteristics (traits) that caused individual members of a species possessing
the trait to produce more adult descendants than those not possessing the trait.
Darwin’s concept plausibly fits the vast majority of observed traits and is
widely thought to be a comprehensive explanation for the evolution process.
Why are genetics discoveries important to evolutionary mechanics
theories?
Are there current scientific disagreements regarding evolution theory?
There is very little disagreement
regarding the fact
of evolution. Current species are descended from earlier and different species
and the evolution of Earth life has progressively and accumulatively continued
for billions of years starting from single-cell organisms. Darwin’s
survival-of-the-fittest concept plausibly fits the vast majority of observations
concerning organism designs. However, some observations, specifically including
biological aging and animal altruism, did not fit leading to multiple proposed modifications to
Darwin’s evolutionary mechanics concept.
What is the main current disagreement regarding evolutionary mechanics?
The main current disagreement
concerns the degree to which the growth and non-extinction of a species population
affects the evolution process relative to the survival and reproduction of
individuals. This issue is crucial to aging theories because there is wide agreement that
aging reduces an individual's
ability to reproduce, at least in mammals. There are now multiple theories to
the effect that aging increases
a population’s ability to avoid extinction and grow.
What is an evolutionary theory of
aging?
An
evolutionary theory of aging attempts to explain how aging relates to the
evolution process and more specifically, why senescence varies so much between
species and otherwise resembles evolved inherited species-specific characteristics
(traits) of organisms.
What is an evolutionary
non-programmed theory of aging?
Modern
non-programmed (non-adaptive) theories of aging suggest that there are many
natural deteriorative processes that act to limit lifespan and that the
evolutionary need to combat these different processes decreases with age. Therefore,
different species only evolved and retained the internal ability to combat the
deteriorative processes to the extent necessary to produce a
species-specific lifespan.
What was Peter Medawar’s key
evolutionary mechanics concept regarding aging?
Medawar
suggested that the force of evolution toward living and reproducing longer under
wild conditions declines with age in a species and population-specific
manner. Lack of internally
imposed senescence would provide little benefit to a population beyond the age
at which essentially all of the members of a wild population could expect to be
dead from external causes such as predation, disease, and starvation.
Why was Medawar’s concept crucial
to modern aging theories?
Medawar’s
concept (1952) explains why biochemically and physically similar species that
presumably have similar exposure to natural deteriorative processes frequently
have very different internally determined lifespans.
What is phenotypic linkage and why
is it important to evolutionary mechanics theories?
Most
elements of an organism’s design have a relationship with the other elements.
Therefore, changing any one element (e.g. femur length) typically requires
complementary “linked” changes to other design elements such as muscles,
tendons, and blood supply to result in a net fitness benefit. This has
implications for the nature of the evolution process, particularly regarding
time-scale.
What is a genomic linkage and why is
it important?
The
genomic design of an organism can cause otherwise unrelated phenotypic traits to
be linked to each other in such a way as to inhibit the evolution of an organism
design that contains one of the traits without the other. Multiple aspects of a
diploid
organism’s genomic design such as pleiotropy, chromosomes, and genetic distance
can result in such a genomic linkage.
Why is selective breeding not like
evolution?
Selective
breeding is directed at enhancing or attenuating a few organism traits that vary
between individuals capable of being interbred with relatively little concern
about inadvertent changes to other traits and operates on a very short time
scale. Evolution is concerned with the combined net effect of all of an
organism’s traits on fitness and because of many inter-trait linkage mechanisms
is a much more complex and a very much longer process. Evolution can alter
traits that do not vary between individual members of a population because
mutations can introduce new variations.
What is the antagonistic pleiotropy
theory of aging?
The
antagonistic pleiotropy theory suggests that aging is the result of a genomic
linkage between aging and some organism trait that benefits younger organisms.
George Williams (1957) proposed that such an antagonistic linkage between a beneficial
trait and a somewhat adverse trait such as senescence would prevent the
evolution process from overcoming aging despite his observation that aging had
some adverse effect on a wild population.
What is pleiotropy?
Pleiotropy
refers to the observation that a single gene can affect more than one phenotypic
property. Single-gene genetic diseases can have multiple diverse symptoms.
Pleiotropy is one form of genomic linkage.
What is the disposable soma theory
of aging?
The
disposable soma theory of aging suggests that because maintenance and repair
activities required to sustain life consume significant material and energy
resources, a species could trade longer survival and reproduction opportunity in
older organisms for increased reproductive activity in younger organisms. This
idea is an extension of Medawar’s idea that the evolutionary value of survival
and reproduction declines with age. Consequently, the evolution process evolved
a design that purposely decreased maintenance and repair in older organisms to
allow more resources to be applied to reproduction in younger organisms.
What is the population vs. individual
controversy in evolutionary mechanics?
Darwin’s
evolutionary mechanics concept is very individual-oriented: The evolution
process selects traits that aid an individual possessing the trait to survive
and reproduce better than an individual lacking the trait. Subsequent
evolutionary mechanics theories are more population-oriented and consider that
the evolution process is driven by characteristics and needs of a population.
Evolution operates to increase the chance that a population will avoid
extinction. There are still fierce arguments as to which or which combination of
theories is correct.
What is group selection?
Group
selection is one of a family of post-1960 theories to the effect that a benefit
to the survival of a group of individuals can offset individual disadvantage and
cause the evolution of an individually adverse trait like senescence or animal
altruism. Variations
of this idea (e.g. kin selection, small group selection) vary mainly regarding
the size of the population considered. Some programmed aging theories are based
on this idea.
What is a programmed aging theory?
Programmed
aging theories suggest that internally limiting individual lifespan beyond a
species and population-specific age creates an evolutionary benefit for a
population of those individuals and that therefore the evolution process caused
the development of biological mechanisms that purposely limit individual
lifespan. Aging is genetically programmed like growth or puberty or mating
seasons. Many different population benefits from limiting individual lifespan
have been proposed.
What is evolvability theory?
Evolvability
theory suggests that an organism’s ability to evolve (i.e. evolvability) can
itself be affected by evolved organism design characteristics (traits), and that
further, a trait that increases evolvability can be evolved and retained even if
it causes some individual disadvantage. An increase in evolvability benefits a
population by allowing it to adapt more rapidly or precisely to changes in its
external world. Evolvability is one of the post-1960 population-oriented
theories.
What is an evolvability-based aging
theory?
Aging
theories based on evolvability contend that internally limiting individual
lifespan increases evolvability in multiple ways and thus increases a
population’s ability to avoid extinction. The first such theory was published by
Weismann in 1882.
What is negligible senescence?
Negligible
senescence refers to the observation that some species (e.g. Pacific
Rockfish) apparently do not age,
that is, do not exhibit measurable age-related decline in fitness parameters
like strength, speed, sensory acuity, susceptibility to disease, or reproductive
ability.
What is maintenance and repair in
connection with aging theories?
Living
organisms have very extensive capabilities to prevent or repair damage from many
deteriorative processes such as injury, wear and tear, infections, cell death,
etc. Many aspects of senescence appear to be caused by progressive decrease in
the effectiveness of maintenance and repair functions. Multiple aging theories
incorporate maintenance and repair.
What is the caloric restriction
effect?
The
caloric restriction effect refers to the observation that restricting an
animal’s access to food often increases lifespan (up to a point), especially in
smaller mammals.
What is Hutchinson-Gilford
progeria and why is it significant to aging theories?
Hutchinson-Gilford
progeria is a very rare human genetic disease that grossly accelerates many
manifestations of aging. This is a clue that there are causes of senescence that
are common to many manifestations and thus favors programmed aging theories.
What are the major medical
research issues surrounding aging theories?
The
current major issue is whether or not senescence, per se, is a medically
alterable and therefore treatable condition. Can pharmaceutical agents and
treatment protocols be devised that generally delay senescence and thereby delay
the appearance of all or most manifestations of aging including serious highly
age-related diseases? Non-programmed theories suggest the answer is “no,”
programmed aging theories suggest the answer is “yes.” The different theories
also suggest that very different biological mechanisms are ultimately
responsible for age-related diseases and conditions and therefore suggest
multiple different paths toward treating such diseases.
Further Reading on Aging Theories:
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