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 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. I wrote up this topic recently, as a new study was done based on 100-year-old twins, and found that only an insignificant handful of mutations over a long lifetime.
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.
Cicadas 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.
* “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.
Hi Josh and thank you for your great blog and many insightful posts. I’ve been an avid reader for some time now.
Did you notice the recent publication of this study about biomarkers that seem to accurately predict mortality? http://www.fimm.fi/en/news/novel_blood_screen_reveals_risk_of_dying_among_healthy_people/
Would love to hear your comments. All the best, Mika
Thank you, Mika – no I wasn’t aware of this, and I’m very interested. I believe there exists the possibility that just “treating the symptom” by re-adjusting some of these blood factors may in itself be a strategy for driving down mortality. I’m going to pass this around, learn more about it, and I’ll let you know what I find.
This makes so much sense. It explains why people who have made a habit out of exercising tend to look much younger than their peers who happen to be the same age as them but are less fond of the idea of exercising. We live in such a technical world, so much so that we have developed an expectation for human beings to be some sort of machines forgetting that humans are actually living beings. I see, one cannot eliminate aging completely, there is just no getting around it, however, one can most certainly slow it down. The secret to doing so is STAYING ACTIVE ! As you have already mentioned aging is more of a self-destruction mechanism than it is a wearing out mechanism, I suppose it is safe to say that healthy eating can have just as big an impact as exercise right ? By eating healthy food we boost the functioning and the repair of the components of our bodies that tend to self-destruct, right ? I must say, this article was very interesting, as a matter of fact I’m thinking of joining a gym …
Josh: Would love to know what some of your contributors think of this product from Dr. Al Sears (not Barry Sears), who is out there hawking a telomere regeneration/rejuvenation formula. A look at the product ingredients is….interesting. I am skeptical, wonder if you and some of your contributors are for the same reason.
Thanks for sending this, George. In the ingredients list, I see a lot of expected ones – overlap with Product B. (Product B is my reference because primary data on telomerase activation is so scarce, and at least I understand how Product B was vetted, and I trust Sierra Sciences, which did the research behind it.)
Comments on specific ingredients:
Alpha Ketoglutarate is a muscle-building supplement.
N-Acetyl Cysteine is a supplement that increases glutathione levels, which I think is a good idea, though unrelated to telomerase.
I’ve seen nothing in the primary literature relating Kudzu to telomerase. The only references I’ve been able to find go back to Sears himself.
There is some literature concerning ginseng as as a telomerase inhibitor.
Stilbenes are chemical cousins of resveratrol.
Half the recommended dose (11 g) is unaccounted for in the ingredient list.
Vitamin C is the largest single ingredient, 14% of the total dosage.
Citrulline is an amino acid.
Nothing in the mix would seem to justify the price Sears is charging.
“So yes, some loss of information is inevitable over long enough times but no, this is not relevant to aging.”
Not to mention if this was true, how to explain life itself lasting for so many millions of years… every generation would eventually produce mostly deleterious mutations and only the few who mutated just at the right place to generate something either beneficial (which is rare) OR neutral (which would make the prospects for the next generation even direr) would survive. Eventually there would be not enough resources (either energy, matter or time) to generate “young youngsters” (sorry for the pun =)) before the progenitor aged itself and died.
Ever looked at an adult human lung? There is a significant amount of material that is deposited from the air we breathe into the lungs. It shows up as many black spots, and remains even after using a detergent to remove the cells. The body simply doesn’t have any mechanism to remove this material. This sort of damage occurs all over the body. Molecules and material build up that just simply cannot be expelled and it ends up causing all sorts of problems that can lead to death. Similarly, material (such as plaque) builds up naturally. The body simply can’t get rid of it. While it may be possible to engineer the body to clean up some of this material, or to prevent “self destruction”, this is quite a difficult task and it is unlikely to be successful to extend lifespan with our lifetimes… certainly yours.
I agree that there is more to aging than simply wearing out, but wearing out is a major portion of the problem. Consider also that stem cell derived replacement tissues would likely be younger tissues with greater regenerative capacity. Growing replacement parts is the most feasible and immediate route to significantly extending lifespan. Certainly, it isn’t the only solution. You can’t simply make a replacement brain. Replacement parts would nevertheless solve many medical problems that would ultimately lead to death.
-B.S. Cell and Molecular Biology
-Grad Student Biomedical Engineering
-3 years stem cell/dev bio/tissue engineering research; 3 years synthetic biology research
-Been interested in aging, replacement parts, and life extension for about 15 years now. Interesting blog. I do recall coming across it several times over the years.
Do you work at SENS or something? Do you have a ‘skin in the game’ (pun intended) of aging paradigms (wear&tear vs programmed)? If not, why are you being so cruel? Hope is much more productive than doom&gloom. Technology is progressing faster and faster, our illusion of knowledge may change sooner than we think.. well, certainly mine will.
Your not making any sense . We are meant to die from organ expiration not diseases . Everyone has to die but not from diseases like heart attacks, cancer, diabetes if you eat right chemical free whole foods . Go back in biblical times in Genesis none of the great men died from diseases but from organ expiration [ organs gave out ] . So you have to die and if you don’t die from diseases then it would be your organs get weak and stop working natural causes .