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Aging Is Not a Process of Wear and Tear
The idea that bodies wear out with age is so ancient, so pervasive, and so deeply rooted that it affects our
thought in unconscious ways. Undeniably, many aspects of aging, e.g., oxidative damage, somatic mutations,
and protein cross-linkage are characterized by increased entropy in biomolecules. However, it has been a
scientiﬁc consensus for more than a century that there is no physical necessity for such damage. Living systems
are deﬁned by their capacity to gather order from their environment, concentrate it, and shed entropy with their
waste. Organisms in their growth phase become stronger and more robust; no physical law prohibits this
progress from continuing indeﬁnitely. Indeed, some animals and many plants are known to grow indeﬁnitely
larger and more fertile through their lives. The same conclusion is underscored by experimental ﬁndings that
various insults and challenges that directly damage the body or increase the rate of wear and tear have the
paradoxical effect of extending life span. Hyperactive mice live longer than controls, and worms with their
antioxidant systems impaired live longer than wild type. A fundamental understanding of aging must proceed
not from physics but from an evolutionary perspective: The body is being permitted to decay because systems of
repair and regeneration that are perfectly adequate to build and rebuild a body of ever-increasing resilience are
being held back. Regardless of the reason for this retreat, it should be more fruitful to focus on signaling to effect
the ongoing activity of systems of repair and regeneration than to attempt repair of the manifold damage left in
the wake of their failure.
It is an an idea so common, so embedded in the thought
process of gerontologists and medical practitioners that it
is seldom questioned: Aging is a physical process of deteri-
oration, because damage accumulates faster than it can be
repaired. At least since the Renaissance, scientists and phi-
losophers, poets, doctors, and laymen have adopted this
understanding of aging. It remains the basis of a great deal of
medical research today, and it is at the core of the Strategies
for Engineered Negligible Senescence (SENS) program. But
despite its ubiquity and common sense appeal, this idea was
thoroughly discredited by physicists of the nineteenth cen-
tury, and their analysis remains cogent. Evolutionary bi-
ologists, who claim the high ground in understanding of
deep causes in biology, have for the last century regarded
damage as a result, not a cause of aging.
In this article, the theoretical relationship between life and
the Second Law of Thermodynamics will be clariﬁed, and
reasons to suppose that physics requires living things to
age will be deconstructed. Some predictive failures of the
‘‘Damage Theory’’ will be catalogued. Finally, if the enor-
mous range of natural aging rates—at least six orders of
magnitude—is not sufﬁcient reason to discredit the idea that
aging is inevitable, then certainly the existence in nature of
organisms that do not age at all must be a disproof.
History of Thermodynamics
The idea that order spontaneously and universally dis-
solves to disorder is very old, but it was not until 1850 that
this notion was codiﬁed quantitatively as the Second Law of
is credited with incorporating
entropy as a quantitative physical variable. He distinguished
ideal ‘‘reversible’’ processes from the ‘‘irreversible’’ processes
that take place in the real world and demonstrated that ideal
processes conserve entropy, whereas in realistic cases, en-
tropy must always increase. The Second Law of Thermo-
dynamics is sometimes stated thus: In any closed physical
system, the entropy will increase, until it attains its maxi-
mum value. The state of the system in which entropy realizes
its maximum value is called ‘‘equilibrium.’’
The Second Law explains why a rock tumbles down a hill,
turning its potential energy of gravitation into low-grade
heat. Metal fatigue and oxidation are familiar examples of
irreversible processes in which entropy accumulates. But the
Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, Arizona.
Volume 13, Number 2-3, 2010
ªMary Ann Liebert, Inc.
law applies only to closed (isolated) systems, and it is pos-
sible for processes to accumulate information in one object,
while entropy is dispersed elsewhere. For example: As a pool
of water evaporates, the liquid can cool (lower entropy) be-
cause the gas disperses with higher entropy that more than
compensates. If there is salt in the water, the salt may congeal
into a crystal as the water disappears. The crystal has much
lower entropy than the dissolved species. It is the water
vapor that carries the higher entropy. The disequilibrium
between the liquid water and warm, dry air above it was
sufﬁcient to drive the process and create the crystal in its
highly ordered state.
Living things have taken this loophole in the Second Law
and developed it as a specialty. The ongoing ability to gather
free energy from the environment and concentrate it as order
within, while discarding entropy as waste is a deﬁning
property of living systems. Every multicellular organism is
capable of growing from seed into a fertile adult. Typically,
the mortality risk of the adult is lower than the immature
stage, and certainly the fertility is (by deﬁnition) higher. So
growth and development constitute ‘‘negative aging’’ in both
the biological and the thermodynamic senses. There is no
theoretical reason this process could not continue indeﬁ-
nitely. The organism could continue to grow larger, more
fertile, and more resistant to mortality of all sorts after it
attained maturity, and some, in fact, do just this.
explanation of senescence, we should appeal to evolutionary
theory, not to thermodynamics.
If living organisms wore out like machines, there would
be no need for an evolutionary account of aging. But mul-
ticellular life succeeds in the remarkable feat of constructing
a complex system from fragments found in the environment,
using only a genetic blueprint, only to fail at the seemingly
much more modest task of maintaining the completed soma
in reasonable working order. In the generation after Charles
Darwin, August Weismann articulated the essential biolog-
ical conundrum of aging and sought an explanation not from
physics but from evolution. Weismann is credited with the
ﬁrst evolutionary theory of aging, but his departure from
physical wear and tear was not so clean. His original theory
was based on a presumption that damage to the adult soma
was unavoidable and that damage must accumulate over
Weismann backed away from this theory later in his life
and wrote instead of the loss of immortality in somatic cells,
as it became an unnecessary luxury. But it was not until Peter
Medawar that the essential logical ﬂaw in Weismann’s
original hypothesis was articulated: ‘‘Weismann assumes
that the elders of his race are worn out and decrepit—
the very state of affairs whose origin he purports to be
inferring—and then proceeds to argue that because these
dotard animals are taking the place of the sound ones, so
therefore the sound ones must by natural selection dispos-
sess the old.’’
Medawar realized full well that there is no thermody-
namic necessity for wear and damage to accumulate. He
sought not a physical explanation for aging, but an evolu-
tionary explanation, grounded in the declining force of nat-
ural selection with age. The evolutionary community has not
looked back, and today there is broad agreement that aging
cannot be explained as a physical necessity, but must be
understood like every other biological phenomenon in terms
of natural selection.
Is Somatic Repair a Difﬁcult or Expensive Process?
It has been argued (most famously by W.D. Hamilton)
that repair of the adult organism cannot be perfect, and that
errors in repair and maintenance must inevitably accumu-
late, leading eventually to the organism’s demise. This is also
a premise of the Disposable Soma theory of T.B. Kirkwood.
But the reasoning is logically ﬂawed, as James W. Vaupel
has demonstrated. There is nothing perfect about a freshly
minted adult, and the maintenance of that adult is not a
process that demands perfection. For example, when a bone
is broken, it knits back together in a few weeks’ time. The
bone was not perfect before it was broken, and it is not
perfect after it heals. But mended bones are stronger than the
original and will not break again in the same place. Bone
repair may be said to be better than 100% efﬁcient and
clearly requires a ﬁnite amount of free energy.
The mammalian body is equipped with an impressive
array of repair mechanisms, from the molecular level up to
the tissue level. Proteins are recycled into constituent amino
acids when they become damaged; it is only in aged animals
that the this process becomes inefﬁcient.
DNA is constantly
monitored and repaired. Underperforming mitochondria are
eliminated and replaced under control of the cell nucleus.
And whole cells are routinely destroyed via apoptosis and
replaced when they become damaged.
All of these pro-
cesses are adequate in youth to maintain the organism
without loss of function, and they fail progressively as a
result of aging, causing aging damage to accumulate. But
their efﬁciency in youth attests to the fact that repair can be
as efﬁcient as it needs to be.
Loose analogies may suggest that at some point in the life
of an organism, damage accumulates to the point where
repair of the organism is energetically less costly than re-
placement through reproduction. This idea is implicit in the
foundation of the Disposable Soma theory.
rience with man-made appliances lends credibility to the
idea; but many of the reasons that a 10-year-old car can be
replaced more cheaply than it can be repaired do not have
analogs in the world of biology. Autos must be dismantled
before they can be repaired and reassembled afterward,
whereas biological organisms repair themselves from the
inside out. Auto manufacturers price the new car with a low
proﬁt margin, and overcharge for replacement parts, because
the customer has nowhere else to go. Auto repair is pur-
chased at market rates for European or American labor,
while cheap Asian labor and cheaper robots are used by
factories in which the autos originate. Thus, we should not
expect our intuitions about automobiles to apply to living
The energetic cost of repairing an aging soma is substan-
tially less than the the total energetic cost of reproducing one
new adult. Repairing DNA and stringing together amino
acids are both processes with low intrinsic theromodynamic
costs and both have been highly optimized for energy efﬁ-
ciency. In contrast, the cost of anabolism is quite substantial,
and the cost of reproduction is magniﬁed by high mortality
AGING IS NOT A PROCESS OF WEAR AND TEAR 323
rates of the immature. For example, a female mouse con-
sumes twice as much food energy while pregnant and lac-
All of this suggests that an enormous quantity of
resource has been consumed to create a single mature adult,
and evolutionary pressure to protect and preserve that in-
vestment ought to be correspondingly high.
A few mammals and many lower animals are capable of
regenerating whole body parts after dismemberment. Ellen
has shown that this capability is latent in
mice as well and can be switched back on with a simple
blood factor. Almost all plants and many animals can re-
generate. The process is expensive relative to repair, but
cheap compared to the full cost of reproducing a new adult
individual. Starﬁsh have a legendary capacity for regenera-
tion, and half a starﬁsh can readily grow back its other half.
And yet, starﬁsh have a life expectancy of about 8 years. If a
limb is severed from a 6-year-old starﬁsh, it regenerates a full
animal that remembers its age, so that it has 2 years re-
maining in its life expectancy. The persistence of senescence,
even in the presence of extensive regenerative capacity, poses
a conundrum: How is the memory of the starﬁsh’s age car-
ried into the young, regenerated tissue?
Tooth wear is an example of true damage accumulation
leading to senescence of the elephant. Elephants can grow six
full sets of teeth in a lifetime, but if they should outlive their
last set of teeth (and some have been found in nature to do
so), they will become toothless and must starve to death. It is
a strange wear-and-tear theory that can explain how it is that
the elephant’s capacity for regeneration ends after its sixth
set of teeth.
Theories of Oxidative Damage
It is over 50 years since Denham Harman
that aging is caused by progressive damage to the body’s
chemistry from the reactive oxygen species (ROS), which are
an inescapable byproduct of respiration. The theory has in-
spired thousands of research projects and continues to have
great currency today. The ongoing attraction of the theory is
that there is broad evidence that oxidative damage to key
proteins accompanies aging. Extensive experimentation has
explored the use of antioxidants as an antiaging intervention,
both in the laboratory and in human epidemiology. The re-
sults of these studies have been disappointing, with the
largest studies actually showing increased mortality for
subjects ingesting antioxidants.
The emerging picture of the
relationship between oxidation and aging is complex: Per-
oxide is an important signal in the pathways connected to
Apoptosis has two faces: It is both an essential
mechanism for cleansing the body of infected, cancerous,
and damaged cells, and is also implicated in the wasting of
and the loss of brain cells in Alzheimer
and Parkinson diseases.
The body’s important antioxi-
dants are expressed at lower levels with age, which both
accounts for the observed increase in oxidative damage
and suggests that oxidative damage is secondary effect
rather than a root cause of aging.
Theories of oxidative damage are elegant and attractive,
but some of the experimental results seem almost to mock
the predictions of the theory. Physical activity generates co-
pious free radicals, and yet high levels of physical activity are
generally associated with longer, not shorter average life
spans. Hanson and Hakimi
report on a genetically modi-
ﬁed mouse that has extra mitochondria. These mice are
phenomenally active, eat much more than wild-type mice,
and burn it all up, yet they live almost 2 years longer than
wild-type mice and remain reproductively active 2 years
longer. Two of the body’s most essential antioxidants are
superoxide dismutase (SOD) and unbiquinone. Mice in
which one copy of the gene for SOD has been knocked out
have half as much SOD in their tissues, and measurements of
oxidative damage to DNA show that it is far higher than
controls; yet the heterozygous Sod2
mice lived slightly
longer than controls.
SOD knockout worms also have ex-
tended lifespan, coupled with enhanced markers of oxidative
clk-1 is a gene originally discovered in worms,
activation of which increases life span by an average 40%.
The homologous gene in mice is mclk1, and its deletion also
leads to enhanced life span.
Only later was it discovered
that the action of clk-1 is essential for synthesis of ubiqui-
none, and, as a result, clk-1 mutants are less able to quench
the ROS products of mitochondrial metabolism—yet they
The ﬁrst data were reported for heterozygous
worms, and it was thought that the homozygous
=mutant was not viable. More careful experimentation
revealed that the =worm developed on a delayed
schedule, and subsequently lived to a record ten times the
normal Caenorhabditis elegans life span.
This worm has no
capacity to synthesize ubiquinone, and its prodigious life
span is truly a paradox from the perspective of the damage
theories of aging.
Naked mole rats live eight times longer than mice of
comparable size, though the latter seem to be better pro-
tected against oxidative damage.
And life spans of mice
are generally a few years, while bats live for decades, despite
a higher metabolic rate and greater load of mitochondrial
The laboratory of Arlan Richardson at the Barshop In-
stitute of the University of Texas reports on the results of an
8-year, systematic study of a wide variety of genes coding for
antioxidant enzymes. For each target gene, they studied both
knockout mice and mice with extra copies of the gene, and
assayed life spans under standard conditions. The only in-
tervention that affected life span was the sod1 gene. They
published their study under the provocative title, ‘‘Is the
oxidative stress theory of aging dead?’’
Circling for the
wounded beast, LaPointe and Hekimi draw a parallel con-
clusion from their own experiments in an article titled,
‘‘When an aging theory ages badly.’’
It is certainly true that much of the damage we associate
with senescence can be traced back to oxidative damage
from ROS created as a byproduct of mitochondrial processes;
but biochemical protections could be adequate to protect
against these hazards with essentially perfect efﬁciency.
Disposable Soma Theory
Kirkwood’s Disposable Soma theory is the only main-
stream evolutionary theory that connects to the idea of ac-
cumulated damage. The thrust of Kirkwood’s idea is that
damage accumulates because the body must budget caloric
energy and skimps on repair to enhance reproduction in a
compromise that optimizes net reproductive ﬁtness. The
biggest problem with the Disposable Soma theory is what it
predicts about the relationship between food energy and
aging. If aging were primarily a matter of insufﬁcient food
energy to both reproduce and repair, then more food energy
would lessen the need for compromise, and the body should
be able to both live longer and increase fertility. The caloric
restriction effect is the oldest, most robust, and best-known
intervention to increase life span, and it is absolutely irrec-
oncilable with the Disposable Soma theory.
It is also a robust prediction of the Disposable Soma theory
that life span should be shortened by the energetically ex-
pensive act of reproduction. In animals, there is no evidence
that this is the case,
and in humans, there seems to be a
small positive correlation between fertility and life span.
Presenescence, Negligible Senescence, Negative
Senescence, and Postsenescence
If aging were a process of stochastic damage, then that
damage would be accumulating inexorably, regardless of
species, of environment, or time of life. The many examples
of nonaging in nature demonstrate that aging is not a
physical necessity. All multicellular life is capable of building
itself up from seed. During the process of growth, aging is
typically absent. In fact, if aging is deﬁned demographically
as increasing mortality rates along with decreasing fecun-
dity, then the early period of growth is a time of negative
Semelparous animals from mayﬂies to octopi may be
distinguished as a subcategory of animals that suffer no (or
negative) actuarial senescence before they die precipitous-
Many plants and some animals do not age measurably
over hundreds of years.
Vaupel has collected examples of
animals that enjoy negative senescence, including coral, sea
urchins, some mollusks and desert lizards.
Fahy offers un-
ique details and adds many more examples, including car-
tilaginous ﬁsh and turtles.
The phenomenon of late life mortality plateaus was not
predicted by any of the evolutionary theories of aging and
certainly not by wear-and-tear theories. It was discovered in
the 1990s that in Drosophila,C. elegans, and humans mortality
rates cease their exponential growth and level off late in life.
(These are the only three animal species for which sufﬁ-
ciently large samples have been studied to detect this phe-
nomenon.) The phenomenon is difﬁcult to reconcile with
damage theories of aging. It must be considered paradoxical
that damage should cease its relentless advance at a point in
the life cycle when repair mechanisms are at their weakest.
If Not Damage, What Then?
The thesis of this work has been negative: Aging of living
organisms is essentially different from the process of accu-
mulated damage that causes inanimate machines to wear out
over time. If aging cannot be explained as a process of ac-
cumulated damage, what then is its cause? The answer must
be sought in the evolutionary process that created life. Be-
cause the aging phenomenon is so ubiquitous in the bio-
sphere, and because genes that cause aging are related over
widely separated taxa, it makes sense to seek a uniﬁed an-
swer to the question of why organisms age.
But the phenomenology of aging is diverse and often
paradoxical, refusing to be tamed by simple, unifying hy-
potheses. The community of evolutionary theorists has no
consensus about the ultimate provenance of aging; instead,
there are competing theories, with the best-accepted ones all
deriving from Medawar’s original insight about the declin-
ing force of natural selection.
It may be that the paradoxical
phenomenology, including results cited herein, is inconsis-
tent with prevailing notions of individual ﬁtness, and that
evolutionary theory will have to stretch to accommodate the
Fortunately, there is a clear message for antiaging research
that does not depend on which evolutionary theory is fa-
vored. The message is that aging is under the body’s control.
If there is no physical necessity for damage to accumulate,
there is also no necessity for bioengineers to invent elaborate
solutions for repairing that damage. It should be far easier to
reprogram the body’s signaling apparatus, turning on
mechanisms that are perfectly capable of maintaining the
body in a state of youthful vigor.
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