No, the body doesn’t just wear out as we get older

Friends often look at me quizzically when I tell them this.  One says, “But I can feel myself wearing down.” And another: “Nothing works the way it used to.  Isn’t that the definition of wearing out?”  And again: “Do you mean it’s all in my head, it’s not really happening?” and then a moment later, “do you mean it doesn’t have to be this way?”

This last formulation is getting a little closer to what I mean.

Of course, loss of function with age is not just in your imagination, and it is very common (though not universal!) in the Animal Kingdom.  But aging is not caused by wearing down.  It is more accurately an orderly program of self-destruction, orchestrated by gene expression.  Some aspects of aging appear as accumulated damage (e.g. cartilage worn away from joints, or build-up of cross-linked sugar-protein complexes), but on closer inspection even these are seen to be entirely avoidable consequences of the body shutting down its repair systems.

This column is devoted to the reasoning and the evidence that tells us aging cannot be, at root, a process of wear and accumulated damage.  First, the theory: why there is no physical necessity for aging; second, a few examples of animals that age very slowly or not at all, and others that age super-fast; third, some familiar facts and a few unfamiliar facts about aging that tell us “wearing out” does not provide a helpful perspective.

 

1. The Physical Theory, and Why it Doesn’t Apply to Living Things

There is no physical necessity for aging.

Man’s earliest conception of aging was that the process was akin to physical wear and tear. Knives get dull – why shouldn’t our teeth?  Wheels get rusty and squeak when they turn – isn’t that what happens to our joints?  Water pipes fill with sediment over the years, just like our sclerotic arteries.  It’s a theory with a great deal of intuitive appeal.

But the analogy between living body andmachine is flawed.  Living things are fundamentally homeostatic.  They can repair themselves.  They build themselves from a single egg cell, and simple animals can rebuild when damaged.  A car takes in energy in the form of gasoline and uses the energy to propel itself forward.  An animal takes in energy in the form of food and uses it to perform all the feats of metabolism, locomotion, foraging, signal processing, and evasion of predators; and a small portion of that energy is devoted to the “capital budget”: breaking down and rebuilding damaged tissues; replicating cells; looking for copying errors in DNA and setting them right, detecting malformed protein molecules, breaking them down into constituent peptides for recycling into new molecules.  This small part of the energy budget is all that is needed to keep the system in good repair indefinitely.

The Second Law of Thermodynamics says that entropy (disorder, degeneration, damage) must increase in any isolated physical system.  But living systems are not isolated.  Living things draw free energy* from their environment, use it internally, then dump waste entropy back into the environment.

This isn’t some lucky feature, tacked on to living bodies, rescuing them from an ironclad law of physics.  The capacity for homeostasis is built into the form and function of living things.  To a physicist, a living body is defined by its ability to create and maintain itself using ambient sources of free energy.  The very function of the living machine is homeostasis (along with reproduction).

Q:  Even though the body is able to repair itself, the repair can’t be perfect.  Isn’t that the root cause of aging?

A:  The repair doesn’t have to be perfect.  The body built itself from seed, created a robust, young individual in the prime of life.  But the body wasn’t perfect when it was young.  Repair can be that accomplished to that same standard.  In fact, it’s always easier to repair a body than to build a new one from scratch.

Q:  When a car gets old, it becomes more and more costly to repair.  Eventually, the mechanic tells you that it’s going to cost you more to fix all the things wrong with your car than to buy a new one.

A:  This is an artifact of mass production.  A new engine is made on an Asian assembly line, with low labor costs and automated manufacture.  Repair requires local, skilled labor, paid at a rate reflecting professional service.  Cars are loss-leaders, artificially cheap; replacement parts are expensive when the manufacturer knows you’ve got no place else to go.  Most important, an engine must be disassembled bolt-by-bolt to get at the worn piston rings deep inside, then meticulously rebuilt; but living tissues are repaird from the inside by efficient molecular machines.

Q:  But think in terms of information.  The DNA is like a book that needs to be copied over and over.  If a single letter is mis-copied, and it evades the error-checking machinery, that represents lost information that can never be recovered. In the long run, the errors have to accumulate, and eventually they will degrade the cell’s ability to function.

A:  This is true, and was the basis of a promising theory of aging in the 1960s.  Experiments were done to test this theory, and it didn’t pan out.  It turns out that DNA replication is designed to be accurate enough that the errors accumulating over one lifetime are not a significant problem.

When stem cells divide to form new, differentiated cells, the old, original strand of DNA stays with the stem cell and the newly-copied strand goes consistently with the differentiated cell.  It seems that Nature has been thinking about DNA copying errors, and has taken care of the problem.

So yes, some loss of information is inevitable over long enough times but no, this is not relevant to aging.  Read more here.

Aging can’t be explained by inevitable accumulation of chemical damage, or DNA copying errors that accumulate, or physical wear and tear, or the accumulated toxic effects of reactive oxidative by-products of the energy metabolism (ROS).  Actually, this much was understood already at end of the 19th Century, when August Weismann wrote a book attempting to explain aging from an evolutionary perspective.

 

2. Aging in nature: fast, slow, and backwards

Aging appears in nature in an amazing variety of forms.  Some of these were abstracted as graphs in a paper I reviewed last month.  In our anthropocentric view, we might imagine that all animals grow up, reproduce in the prime of life, then gradually lose fertility and strength, and suffer accelerating decline leading to death.  This is the way it is for people, guppies, and sea birds.

But salmon and octopuses reproduce all in a burst and quickly die.  The thing that kills the salmon is a burst of corticoid hormones that deranges the fish’s hormonal balance.  What kills the octopus is that its mouth seals closed, and it can no longer eat.

Sharks and clams just keep growing larger and more fertile and stronger and less vulnerable to death as they get older.  The oldest ones are rare and large, and it takes a great accident to kill them, because they are not about to die of old age.

Locusts spend 17 years maturing underground, then come out, mate and die in a single day.  The adult has no organs for eating or digesting food.

Some jellyfish and beetles have been observed to regress when starved.  Their bodies shrink, then progress backward through previous stages of development until they are larvae once more.  As larvae, they can exist in a kind of hybernation, and when food becomes available, they can grow again and start life over.  In the lab, they have been manipulated to go through many cycles of getting older, getting younger, and on and on.

Rockfish are medium-sized, deep water dwellers.  Though most rockfish live 10 to 20 years, occasionally one is caught that is over 200 years old, as determined by annual growth rings in an ear bone.

The fastest life cycles in nature (yeast cells) suffer aging and death in a matter of hours.  The slowest (sequoia trees) aging processes unfold over thousands of years.  If aging is an inevitable physical process, why would it occur a million times faster in some species than in others?

It would appear that aging is a common but optional part of the life plan.

 

3. Response to stress:  Aging doesn’t act as we would expect

If you keep your car in the garage six days a week and drive only to church on Sundays, it will last a long time.  Drive it like a hot rod and it will wear out a lot sooner.  But our bodies last longer the harder we work them.

Exercise generates free radicals like crazy, but the body’s native anti-oxidant defenses overcompensate.  Muscles suffer little tears, bones tiny fractures, and yet the body repairs these better than new, and the result is that we live longer if we exercise.

One of the three mainstream evolutionary theories (the “disposable soma”) holds that aging results from budgeting of energy.  The body apportions its food energy for maximal fitness, not for maximal longevity, so more of it goes to survival and reproduction, less to repair and maintenance.  This theory is utterly untenable in the face of caloric restiction experiments.  Animals quite generally live longer ther less they are fed.  If aging were enforced by the energy budget, a larger energy budget would cause us to live longer.

Finally: Some of the biochemistry of aging is understood now, and its basis looks like self-destruction, not like attrition.

  • Stem cells cease replicating when their telomeres become too short, all because the enzyme telomerase is withheld.

  • Inflammation, which protects the young body against invading microbes, is turned against healthy tissues in old age, damaging arterial walls in particular and triggering cancers everywhere.

  • Apoptosis is cell suicide, which works to protect us against diseased and dangerous cells in our youth, but as we get older we lose healthy, functional cells to apoptosis.  This is the underlying cause of sarcopenia, and is related to the cause of Alzheimer’s disease.

  • The thymus is a tiny gland at the base of the throat, responsible for training white blood cells so that they are smart enough to attack invading pathogens and refrain from attacking the body’s own tissues.  As we age, the thymus shrinks in size and loses its functionality, so the immune system makes errors Type I and Type II:  It attacks the self, causing auto-immune diseases including arthritis, and it fails to attack invaders, making us increasingly vulnerable to infectious disease.

 

The bottom line

Since 1889, mainstream evolutionary science has rejected the idea that the body ages for the same reason that a tool or a machine wears out.  In this case, evolutionary science has it just right.

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* “Free energy” is a technical term in thermodynamics.  It means that portion of total energy which is available for work.  Ambient warmth is energy, to be sure, but not useful energy.  “Free energy” has a well-defined quantitative meaning.  Electric energy is 100% free energy.  Energy in boiling water is about ¾ free energy and ¼ ambient warmth.  Likewise, chemical energy is partially free energy and partially warmth.

Total energy cannot be created or destroyed, but free energy becomes degraded into warmth as it is used.  Both living things and non-living machines take in high-grade forms of free energy, use some of that for their various functions, and discard the same total amount of energy as low-grade chemical energy and warmth.

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This article originally appeared on Josh’s blog here: http://joshmitteldorf.scienceblog.com/2014/04/07/no-the-body-doesnt-just-wear-out-as-we-get-older/

6 Comments

  1. I think your right

  2. Why is it that there has to be free radical damage to make the body repair the damage 100%+? Also that some studies show taking antioxidants stops this repair after exercise? Surely it can be seen outwardly in peoples skin etc, that those who take antioxidants look better. If it were true then everyone with a deficient diet with less antioxidants would look better and function more fit for longer under the same circumstances.

  3. It seems that you’re splitting hairs in a question where it is does not matter if those hairs are split. Aging is caused by a body’s design to destroy itself -vs- aging as body’s poor design in repairing itself sufficiently. This is like asking why in science. You don’t. It is only how, never why. The real question is how to intervene in that design – earlier or later; piecemeal or comprehensively; and which type of intervention gets 150-year old people first and which approach gets 1000-year old people first. Maybe it is the same approach – maybe one or the other or neither or a hybrid. Should aging money be spent on the time it takes to get to the 150-year old ‘healthy’ threshold or the ‘near-indefinite’ range.

    • There is a difference between the two perspectives. If it’s not just wear-and-tear, but rather the body attacking itself, then the problem becomes a lot easier to solve. You would only need to identify and turn off the genes leading the attack, rather than having to create entirely novel biology.

    • Case in point: http://gizmodo.com/scientists-manipulate-genes-to-make-old-organs-young-ag-1561729392

      The thymus (in mice, and likely in humans as well) can be regenerated to a youthful state with a single change in gene expression.

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