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Azinet LLC, Box 239, Crownsville MD, 21032, USA; fax: 14104032283; Email: tgoldsmith@azinet.com
Received June 13, 2013
Abstract—Until recently, nonprogrammed theories of biological aging were popular because of the widespread perception
that the evolution process could not support the development and retention of programmed aging in mammals. However,
newer evolutionary mechanics theories including group selection, kin selection, and evolvability theory support mammal
programmed aging, and multiple programmed aging theories have been published based on the new mechanics. Some pro
ponents of nonprogrammed aging still contend that their nonprogrammed theories are superior despite the new mechan
ics concepts. However, as summarized here, programmed theories provide a vastly better fit to empirical evidence and do
not suffer from multiple implausible assumptions that are required by nonprogrammed theories. This issue is important
because programmed theories suggest very different mechanisms for the aging process and therefore different mechanisms
behind highly agerelated diseases and conditions such as cancer, heart disease, and stroke.
DOI: 10.1134/S0006297913090022
For much of the past century, it was widely thought mechanisms, and sexual reproduction in addition to the
that the evolution process was directed entirely by indi lifespan observations. The new theories were largely based
vidual cost and benefit. An evolved trait had to benefit the on relatively recent genetics discoveries.
ability of individual organisms (or their direct descen Some nonprogrammed aging proponents countered
dants) to survive and/or reproduce. It was also widely that all of the nonindividualbenefit theories were invalid
agreed that deterioration and death associated with aging because of the mechanics of mutation propagation.
did not provide any individual benefit in gradually aging However, multiple proposals appeared [4] providing prop
mammals. Programmed aging requires that there be an agation solutions for the nonindividualbenefit theories.
evolutionary benefit from purposely limiting lifespan. Finally, the zero net evolutionary disadvantage of
Therefore, programmed mammal aging was considered aging proposed by nonprogrammed proponents weak
to be “impossible” and nonprogrammed aging theories ened their argument against programmed aging based on
dominated scientific thought on the subject although nonindividual benefit as outlined below.
numerous issues remained. Consequently, proponents of nonprogrammed
However, beginning in 1962 a series of evolutionary aging have largely abandoned attacks on the nonindivid
mechanics theories appeared proposing that wider bene ualbenefit theories. Some senior and vocal proponents of
fit to groups [1] (group selection), kin [2] (kin selection), nonprogrammed aging have even conceded that the
the propagation of genes [3] (e.g. selfish gene theory), or nonindividualbenefit theories may be valid [9, 10].
the evolution process [4] (evolvability theory) could offset Further, logical attacks on specific programmed aging
some degree of individual disadvantage and result in evo theories based on the many proposed nonindividual
lution and retention of an individually adverse trait like benefits of a purposely limited lifespan have not appeared.
mammal aging. Programmed aging theories then Instead, the remaining proponents of nonprogrammed
appeared [58] that proposed that an organism design aging contend that their theories provide equivalent per
that purposely limited the life of the organism generally formance in matching observations and should have sole
provided nonindividual benefits to most organisms consideration by medical researchers [9, 10]. Major diffi
including mammals. The nonindividualbenefit theories culties with this idea are described below. Researchers
also provided explanations for observations of other indi choosing the wrong theory of aging could significantly
viduallyadverse organism traits including altruism, delay progress in preventing and treating agerelated dis
excessive male puberty age, some aspects of inheritance eases.
971
972 GOLDSMITH
COMMON FEATURES OF PROGRAMMED tion beyond the age at which 100% of the individuals in a
AND NONPROGRAMMED THEORIES wild population could be expected to be dead from exter
nal causes such as predators, environmental conditions,
The following outlines areas for which there is agree or lack of habitat or food supply. Medawar proposed that
ment between modern programmed and nonpro the evolutionary benefit of living and reproducing longer
grammed aging theories. declined to zero at some speciesspecific age as shown in
Intrinsic and extrinsic causes of mortality. Darwin’s Fig. 1 (curve 2). Issues associated with the concept of
[11] evolutionary mechanics concept “survival of the overcoming internal lifespan and reproductive limitations
fittest” (curve 1, dashdotted line in Fig. 1) did not suggest are discussed further below.
that the evolutionary value of surviving and reproducing Aging and reproductive maturity. We can also all agree
varied with the age of an organism. According to Darwin, with Medawar’s proposal that internal factors that caused
organisms were trying to live as long as possible and breed even very slight degradation in survival or reproductive
as much as possible and were acquiring traits through the fitness prior to the age at which the particular species
evolution process that helped in this quest. This concept could complete its first reproduction would be very high
logically leads to the idea that observed lifespans are the ly selected against as shown in Fig. 1. We can agree that a
result of fundamental limitations such as laws of physics or species that died of old age prior to reaching puberty
chemistry that cannot be overcome by the evolution would not be viable. Modern programmed and nonpro
process. However, lifespans in different mammal species grammed theories of aging agree that the age at which an
were observed to vary over a huge range of at least 100 to 1, organism is first capable of reproducing is the most
and fish lifespans were seen to vary over a range of at least important factor in determining the lifespan needed by
600 to 1, from weeks to centuries. In the following 93 years that organism, although many other speciesspecific
theorists were unable to provide a plausible explanation, internal and external factors affect the needed lifespan.
based on Darwin’s evolutionary mechanics, as to why Evolutionary disadvantage of aging. Major pro
there was such an enormous difference in lifespans grammed and nonprogrammed evolutionary theories of
between different species. This led to modern pro aging concur that at some speciesparticular age the net
grammed and nonprogrammed aging theories, all based (counting all tradeoffs) evolutionary disadvantage of
on modifications to Darwin’s mechanics, which propose aging must be effectively zero as shown in Fig. 1, curves 2
that the evolutionary benefit of survival and reproduction (solid line) and 4 (dashed line).
declines with age following reproductive maturity. This is true because in the case of essentially any
In 1952 Medawar [12] introduced the now generally species we can find some similar species with a longer or
accepted idea that the evolution process must incorporate shorter lifespan, and it is therefore apparent that a species
some relationship between internal and external causes of can evolve whatever lifespan is needed by that species. If at
mortality. The evolutionary benefit of overcoming internal that age there was an even very slight advantage to a longer
limitations on lifespan and reproduction (i.e. senescence) lifespan, the species would presumably have evolved a
declined in proportion to the relative importance of exter longer lifespan. Proponents of nonprogrammed aging
nal causes to internal causes. For example, we can all contend that beyond the age (point A) at which the bene
agree that there would be zero evolutionary benefit to fit of further survival and reproduction declines to zero,
overcoming internal limitations on lifespan or reproduc there is no further decline as shown in curve 2. Living
longer creates no evolutionary disadvantage.
Programmed aging proponents contend that based
on modern evolutionary mechanics concepts that allow
1
for nonindividual cost/benefit, further life and repro
duction conveys an evolutionary disadvantage as shown in
curve 4. According to programmed theories, aging and
2
other lifespan limiting traits are beneficial features of
3 organisms that evolved because they cause the possessing
species to have an evolutionary advantage. According to
nonprogrammed theories and curve 2, there is evolu
tionary force only toward achieving the age at which the
value of further survival and reproduction declines to
4
zero. According to programmed theories there is evolu
tionary force toward both achieving the zeropoint age
and not exceeding it. Beyond the zeropoint there is evo
lutionary force toward limiting lifespan, which leads to
the evolution of mechanisms that purposely limit lifespan
Fig. 1. Evolutionary cost/benefit vs. lifespan. to a particular optimum value.
dation, molecular disruption, genetic transcription faults, consequently the associated maintenance and repair
mechanical damage, and other natural processes that mechanisms are presumably very different. If for some
cause deterioration in biological systems. The gross life reason a species needed a shorter lifespan as required by a
span differences are explained by the presence of a large programmed aging theory, or did not need as long a life
number of independent antideterioration functions that span as specified by a nonprogrammed theory, de Grey
act to prevent damage from or repair damage resulting suggests that all of its maintenance and repair mechanisms
from the generic deteriorative processes. A particular would eventually be gradually degraded by random unop
longerlived mammal species possesses more effective posed mutations until the target lifespan was obtained.
antideterioration functions than a shorterlived species Therefore, de Grey suggests his passive maintenance con
and consequently is able to slow the monotonic accumu cept would satisfy both programmed and nonpro
lation of damage. grammed theories of aging in regard to obtaining the
This concept suggests that organisms possess a poten speciesspecific lifespan needed by each species.
tially large number of maintenance and repair functions Figure 3 describes a programmed aging concept in
that are functionally independent and evolved independ which maintenance and repair functions are further con
ently in order to produce the lifespan needed by the organ trolled by a biological clock mechanism. The clock
ism. If, for example, cancer at too young an age was pre directs the various maintenance and repair mechanisms
venting a species from obtaining the particular lifespan to decrease their effects as a speciesspecific function of
needed by that species, the species would evolve better age in order to result in the speciesspecific lifespan. The
anticancer mechanisms. If heart disease at too young an clock mechanism can in turn be adjusted by sensory func
age was a problem, the species would evolve better anti tions that can detect and respond to external conditions
heartdisease functions. It is understood that the mecha that alter the optimum lifespan for the organism.
nisms ultimately responsible for cancer, heart disease, and This concept encompasses the idea that not all phe
other diverse manifestations of aging are very different and notypic changes associated with aging necessarily involve