What Doesn’t Kill Me Makes Me Stronger

Most people over 50 have some kind of joint and back pain.  We think that when we gain weight, there is more pressure in every step, more strain on the joints, and it makes our arthritis worse.  But the truth is stranger than this.  In fact, exercise helps to prevent and to relieve arthritis [Ref1Ref2, Ref3Ref4].  (The only exception is extreme, punishing exercise, like the elbow of a major league pitcher or the knees of a lineman in pro football.)  Walking around with a 40-pound backpack has the opposite effect of carrying an extra 40 pounds of belly fat.  The reason that weight gain exacerbates arthritis is that every fat cell is a hormone factory, pumping out inflammatory signals.  Together these signals (called cytokines) tell the blood cells to turn up the heat on the inflammatory attack that is eating away at the cartilage in our joints.

Was mich nicht umbringt, macht mich stärker.
— Friedrich Nietzsche

Maybe the fact that overeating is bad for our longevity is so familiar to you that you no longer think it’s strange.  But believe me, it’s strange.  It’s strange that the harder you work your body the longer it lasts.  And it’s strange that life span in lab animals can be modestly extended not by protecting and coddling them, but just the opposite–by challenging them with one hardship or another.  A list of things that have been found to increase life span include

  • low-dose radiation
  • toxins
  • pathogens and infections
  • heat, and
  • cold
  • hypoxia (oxygen starvation)

Paraquat is a powerful herbicide, and highly toxic to humans.  It is the opposite of an anti-oxidant.  When paraquat was sprayed from the air to destroy marijuana fields in Chiapas, Mexico, 16 people died.

In the McGill University laboratory of Siegfried Hekimi, life span of roundworms is extended remarkably by adding paraquat to the medium in which they swim.  Tiny doses of paraquat have little effect, and high doses kill the worms, but if the dose is adjusted just right, the worms live 70% longer.

When challenged, the body adapts by becoming stronger–this much is no surprise.  What makes us stand up and take note and rethink how we’re put together is that the body “over-adapts”.  It becomes so much stronger that we actually are healthier and live longer in the presence of challenges and toxins and hardships than when we are coddled in an ideal, unstressed environment

The name for this general phenomenon is hormesis, and it was first described in the 19th Century.  But the word “hormesis” dates only from 1943, and it is only in the last two decades that the idea has received some scientific respect.  There are three reasons the scientific community has resisted the concept:

  • Association with the problematic science of homeopathy.  In the early 20th Century, people who promoted homeopathic medicine were prominent supporters of the concepts of hormesis.
  • Polluters and chemical manufacturers seized on the idea to argue, opportunistically, that pollution is actually a boon to public health!  In fact, owners of nuclear power plants argue that leakage of radiation is not a problem as long as it is below a threshold dose*.
  • The true strangeness emphasized above.  Hormesis implies that the body is unable to be fully healthy if it has all the food it needs, and is deprived of poisons and stressors.

 

Examples of Hormesis

  • The most dramatic and obvious examples of hormesis are that less food and more exercise both lead to extended life span.
  • Chloroform is a trace contaminant in toothpaste.  Manufacturers tested the safety of their product by feeding toothpaste to dogs with and without the chloroform.  They were surprised to find that the mortality rate was lower for the dogs that got chloroform [Ref].
  • Repeated, mild burns slow the age-related damage to human skin cells [Ref].  Worms that are exposed to heat shock also live longer [Ref].
  • In an Australian study, people exposed to more sunlight had less long-term UV damage to their DNA [Ref].
  • Rats that were bathed in cold water 4 hours per day lived longer and had lower cancer rates than rats that stayed warm [Ref].
  • Mice exposed to 25 or 50 times the normal background level of gamma radiation lived 20% longer than mice that received only the ordinary background [Ref].
  • Fruit flies exposed to disease enjoyed greater fertility and longer life [Ref].

Don Luckey devoted the last decades of his professional life to documenting the health benefits of radiation exposure, and faced the skeptics to argue that we should all be getting more whole-body radiation exposure than we get from cosmic rays and low background of radioactive elements in the earth [Ref]. The US National Research Council disagrees [Ref].

Edward Calabrese researches the epidemiology of environmental toxins at U Mass.  For 25 years, he reported findings in terms of standard linear models:  If 1 part per million is bad, then we expect half a part per million to be half as bad.  But with accumulating evidence, there came a point where he had to break ranks, and he has been a prominent advocate of the hormetic viewpoint ever since.

From a comprehensive search of the literature, the hormesis phenomenon was found to occur over a wide range of chemicals, taxonomic groups, and endpoints…hormesis is a reproducible and generalizable biological phenomenon, and is a fundamental component of many, if not most, dose-response relationship [Ref].

The Hygiene Hypothesis says that widespread use of disinfectants has reduced childhood exposure to bacteria to an unhealthy extent, and that increased incidence of asthma, irritable bowel syndrome, Crohn’s disease, and various auto-immune disorders has been the result.

Hormesis also has an unusual place in cinematic history. During the 1950s, reports on the capacity of ionizing radiation to stimulate growth inspired the genre of so-called ‘‘nuclear monster’’ movies, which included Godzilla (1954) and Attack of the 50 Foot Woman (1958). Typical of this genre was Them! (1954), in which ants exposed to radiation from atomic bomb tests grow to gigantic proportions and terrorize residents of New Mexico. [Ref]

 

How to make biological sense of hormesis

The reason that hormesis seems so strange to us is that we like to think that we are evolved to be as strong and as healthy as it has been possible for nature to make us.  It doesn’t make sense for us as individuals to hold back on strength and longevity just because we don’t happen to be starved or poisoned at the moment.  But if we think collectively instead of individually, it all starts to make sense…

My principal contribution to evolutionary theory has been the Demographic Theory of Senescence, which starts from the premise that population overshoot is a danger to most animal species.  If animals eat all the food that is available to them and reproduce as fast is they are physically capable, then the environment will be denuded, the next generation will starve, and the species will face extinction.  All animal species are evolved to avoid this.  [Academic references 2012 and 2006]

Another way to describe this same situation is to say that the main causes of death in nature are all clumped together.  When food becomes scarce, everyone starves at once.  When there is an epidemic, everyone gets sick together.  When there are storms or cataclysms or environmental poisons, they affect an entire population at once.

Aging is nature’s way of leveling out the death rate, assuring that we don’t all die at the same time.  Aging puts our deaths on an individual schedule so we can die at different times; other causes of death tend to kill everyone or no one.

Since aging has evolved to complement the environmental death rate, we expect that when the environment is most hostile, there is little or no need for additional deaths from aging.  So aging takes a vacation during starvation or other times of hardship.  Conversely, when life is easy and stress-free, no one is being killed from external causes, aging is out in full force, helping to thin the population and avoid population overshoot.

So the Demographic Theory provides a natural context for understanding hormesis.  In fact, the Demographic Theory is the only theory of aging in which hormesis is actually a prediction.

(Mikhail Blagosklonny agrees, but stops short of saying that aging is programmed.  Peter Parsons disagrees.)

 

Implications for Personal Care and Longevity

Well, eat less and exercise more–that’s a good start.  If I were just looking at the data, I’d have to say that introducing a source of gamma radioactivity in the home, 25 times above background might be justified.  But the idea makes me queasy.  We don’t know how to do it well.  Might it be beneficial at some ages and a risk factor at other ages?  People who live in houses with naturally high radon levels have elevated risk of lung cancer [Ref].

The concept of hormesis has made me relax a lifelong fear of pollution, and I have backed off from Bruce Ames’s program of reduced exposure to natural and artificial toxins. But I’m not ready to do anything pro-active to increase my exposure to toxins or radiation.

 

———————–

* My position on nuclear power is that low-level leaks of radioactivity are the least of its problems.  Nuclear power should be a non-starter because it is uneconomic without huge government subsidies, including the Price-Anderson act which limits liability.  Haven’t we learned anything from Chernobyl, Three Mile Island, and Fukushima?  And don’t get me started on guaranteeing the safe storage of radioactive waste for the next 20,000 years.

26 thoughts on “What Doesn’t Kill Me Makes Me Stronger

  1. Seems like this could apply to an individuals psychology as well. Stress the mind, and over time become immune to depression, adhd, or other mental illnesses.

  2. I am used to find always a practical meaning for everything I read, so I couldn t help it not to imagine my self in a 4 hour cold bath, making CT s and PET scans every day, while ingesting low doses of agent orange 😀
    Anyway ,very interesting reading! Makes sense theoreticly.

    • I see a daily swim as better than a bath. Swimming always lifts my spirits, and i think I’d get chilled pretty quickly if I were lying still in a cold bath.

      The rats in the cold water experiment burned a lot more calories, as evidenced by the fact that they ate more but did not gain weight.

  3. I’m sure your sources are correct but the view and sample data are biased. Cancer rates, as you note, go up with radiation and also withUV exposure. You make a dangerous point that some people who don’t read carefully might buy into fast and make poor decision. A warning at the top of the post or another analysis of the effects of these exposures, on a large sample that also presents the downsides would be more balanced.

    • I think my feet are in good shape with radiation. When I was a child, the shoe stores all had X-ray machines. I would put on my new shoes and stick my feet under the X-rays. It would show my foot bones; so that the salesman could tell me whether or not my shoe fit properly. Last time I was in the hospital, they gave me a chest X-ray every day, so my chest is good too, not to mention my teeth, also. Years ago the smog was thick enough to smell. When I got to the far side of the street, I had to bend down and feel for the curb; so I guess my lungs are good to go.
      At 74 I still lift weights and get stronger every month; so Josh must be right! Now if I can just quit eating; it is a dangerous habit and hard to break. 😉

  4. Interesting article. Regarding the footnote on the nuclear industry – its important to note that the existing design (and fuels) used for nuclear power seem to have been chosen directly (i.e. early development funding) as a result of them producing materials for weaponisation. There are much better designs which are safer (run away reactions aren’t possible), practical and cheaper (both at the front end and the back end of the lifecycle) and which use other fuel sources – such as Thorium – we absolutely should be looking at using in preference to the existing reactor technology. Its really important to distinguish between these and not just label the whole lot as “nuclear power”, which comes with it the baggage the existing technology (rightly) carries with it….

    • I agree that some forms of nuclear power are worse than others. But the price of nuclear is rising and the price of photovoltaics is already lower, and is falling. Cheaper than either is the cost of saving energy at the point of end use, which is still a great untapped resource of “negawatts”, as Amory Lovins likes to call them.

  5. “Haven’t we learned anything from Chernobyl, Three Mile Island, and Fukushima?”

    Yes, I’ve learned that the total number of deaths from radiation accidents in the history of the world, for outdated reactor designs, with incompetent operators, or after having withstood the 5th largest earthquake in recorded history, is still less than the number of people who die in car crashes in America every month, or from cigarettes every 3 days.

    We could have 10 Chernobyls a year in America and secondhand cigarette smoke would still be the bigger health risk.

      • You really shouldn’t quote Helen Caldicott or Amory Lovins; reading them is fine but only to dismiss them.
        Chernobyl has so far killed about 60, and based on actual studies of Nagasaki and Hiroshima (and not made up hypotheses), about 4,000 people should die earlier than otherwise from cancer.

        Waste storage is an overblown problem. Long term waste from 50 years of French nuclear industry (75% of its electricity is nuclear) has the volume of just two olympic pools.

        • Nuclear power is uneconomic by any standard, regardless of its environmental impact. The price of photovoltaics is already lower than nuclear and is falling, while the price of nuclear power is rising.

          The environmental impact of nuclear power is difficult to estimate because it is so episodic, and each episode is different. Also because of the nuclear waste problem. It is pure hubris to be living our lives in a way that leaves a legacy of poison to our descendants 1,000 generations into the future. Where would we be today if every generation for the last 20,000 years had had that attitude toward the planet they were leaving to us?

  6. The idea that caloric restriction extends life is not as set in stone as pop-culture might lead you to believe: http://www.nytimes.com/2012/08/30/science/low-calorie-diet-doesnt-prolong-life-study-of-monkeys-finds.html?pagewanted=all&_r=0

    In humans, there are many studies that seem to indicate the Body Mass Index associated with the longest life span is actually around 27.0 (at the low end of the ‘overweight’ category).
    http://www.medpagetoday.com/Endocrinology/GeneralEndocrinology/44843

    • Take a look at my article on the rhesus monkey CR studies. The two studies are not a reason to doubt the general efficacy of CR.

      Re: BMI=27 – There is a genetic component and a life style component to weight. The genetic component does not affect life span, but the life style component does. Many women who have BMI=27 are in fact restricting their diets to keep from being heavier. Many women and men who have BMI=21 feel no need to restrict their calorie consumption because they look great. Read more here.

  7. Dear Josh,

    thanks for your thought provoking article!

    I wonder how this theory of “more strain lets you live longer” fits with the observation that socioeconomic status is positively correlated with good health and life expectancy.

    According to your proposed theory, shouldn’t one expect it to be the other way round? So that people who live convenient lives in affluence should have a lower life expectancy compared to, for example, homeless people or poor people or people in third world countries, who suffer various kinds of hardship.

    Is there more human population based observational data (apart from the radiation example you mentioned) that fits with your theory?

    Thanks
    –Frank

    • The data tell us there are two kinds of social stress. Taking on a lot of responsibility, feeling important and that others’ wellbeing depend on on us – this is pro-longevity. But feeling powerless and demeaned and under someone else’s thumb – this kind of stress cuts your life short. There may be stories to explain this from social evolution as well, or maybe they’re just stories…

  8. I’ve always wondered if there was a term for this phenomenon; now I know. 🙂

    I think the more general phenomenon at work here is: expose a system to stress and it will work to overcome that stress, while the newly gained strength used to overcome the stress will persist even after the aversive conditions have been removed. For example, a website fortifying its security after a security breach.

    • I guess I haven’t convinced you of the essential strangeness of this phenomenon.
      In real life, a website doesn’t wait for a security breach, but learns from the experiences of others. Why haven’t our genes learned from millions of years of stress to protect themselves maximally even without the starvation or the toxins? What is it that the body is able to do when it is starved and poisoned and running as fast as it can that it can’t do when unstressed?

  9. This assumes that the organism is able to strongly adapt and has the necessary energy and nutrients to successfully do so. I assume the organisms studied in these labs are well-fed. Humans and animals in the wild often are not well-fed, at least not nutritionally…what then??

    • These are good things to think about. The number of experiments you could concoct if you combine stressors multiplies quickly, and it’s not quick or cheap to do these mouse life span experiments.

      But it’s generally true that cutting back food extends life further. This is true even if life span is already extended with vigorous exercise. I expect it would also be true if the mice were exposed to toxins or low-dose radiation as well. But the experiment hasn’t been done, to my knowledge.

  10. Hi Josh,

    Presumably you’ve read Taleb’s recent book Antifragility. It centers around hormesis and how Mother Nature uses it to make a species stronger.

    His recommendations for health focus on via negativa advice, i.e., try to remove things that are hurting you rather than adding things that could help you. He believes that the trade-offs for taking some supplement or medication when you’re not sick/marginally sick are not worth it. However, if you’re very sick or close to dying, then he believes you should try anything. Based on his advice I’ve caught out basically all supplements and just try to eat healthy and exercise regularly.

    His only medical advice, besides via negativa, is to practice hormesis (lift heavy weights irregularly, walk a lot, take cold showers, intermittent fasting) and consume foods/liquids that have been around for millennia and that your ancestors would’ve eaten.

    • There is an argument that hormesis is inconsistent with the paleo diet. It’s too much for this comment box, but you can read it here.

      There are a few drugs that have been found to extend life in rodents and lower mortality in humans. I recommend melatonin, aspirin, vit D, metformin on this basis. Lots of exercise. Swimming is a double plus. Low-carb diet and fasting. More details at AgingAdvice.

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