Anti-aging Oxymorons and         Anti-oxi-morons

The natural foods industry is deep into the anti-aging business, and it’s all based on two lies—one about pesticides and toxins, the other about anti-oxidants.  Neither toxins nor oxidation are the reason that we get old, and we can’t live longer by eating less toxins or more anti-oxidants.  In fact, toxins in small quantities stimulate the body’s longevity pathways, and anti-oxidants can nullify the very real anti-aging benefits of exercise.

People who are fanatical about clean air and organic food don’t live to extraordinary ages.  Animals raised in a super-clean, toxin- and pathogen-free environment actually die earlier than animals raised with bugs and dirt.

Anti-oxidants have been tried in animal experiments and human studies, and they don’t extend life.  In a definitive study, 29,000 Finnish men were given anti-oxidant vitamins in the 1990s, until the experiment was called off for ethical reasons.  It turned out people taking the vitamins were dying at a higher rate than the placebo group.

“Natural anti-aging” is a contradiction in terms, an oxymoron.  There are plenty of good reasons to eat organic.  Support more sustainable farming practices.  The vegetables taste better.  There’s more nutritional value and it might even be healthier, especially for young people.  But natural foods are not part of the recipe for a longer life.

In fact, there is plenty you can do to slow down aging and improve your odds for a long life, but the best practices aren’t particularly “natural”.  Weight loss, fasting and short bursts of vigorous, all-out exercise are high on the list.  There are also some hormones and two prescription drugs* (long out of patent) that seem to work.  The easiest thing you can do to improve your odds is to take tiny doses of aspirin and mega-doses of vitamin D. (Much more here.)

 

What aging really is

Aging is not about the body wearing out, and it’s not about accumulating  toxins.  Aging is something our bodies are doing to themselves.  All the stuff that goes wrong as we get older is no accident, and it’s not a failure of the body.  Aging is suicide on a schedule, programmed into our genes.

  • The stem cells in our body are tasked with renewing our skin and muscle and bones and blood, and even our nerve cells regrow over time.  But the stem cells have replication counters in the chromosomes.  Regular readers of this page are familiar with telomeres and “cellular senescence”.  Telomeres are the body’s primary aging clock; when the counter gets too high, the stem cells get the message to slow down growth and repair, to let the body go to pot.
  • Our immune system is brilliant at distinguishing invaders from self, attacking the former and protecting the latter.  This is done by the T-cells in our blood.  The T in T-cell stands for “thymus”, a little organ behind the breast bone where T-cells are trained to tell the good guys from the bad guys.  But your thymus has been shrinking ever since you were about 10 years old, and by the time you’re 40, it’s only ⅓ what it was when you were a child.  90-year-olds have almost no thymus left, and that has everything to do why 90-year-olds can’t defend against the flu, and why pneumonia is the Old Man’s Friend.
  • The T-cells don’t just fail to defend us against enemies, they make the opposite mistake as well, and attack perfectly good, healthy tissue.  Inflammation is your first line of defense against invading microbes when you’re injured, and it works great when we’re young.  But as we get old, inflammation turns inward.  Healthy cells are destroyed.  Stem cells are re-purposed as cancer cells.  Inflammation has been linked to the Big Four diseases of old age which, together, are responsible for more than 90% of all deaths:  cancer, heart attacks, Alzheimer’s dementia, and stroke.
  • There are more ways in which the body actively destroys itself in old age.  Read some of them here.

These aren’t failures of the body.  They’re mutiny.  We can’t fix these problems by supporting the body with a natural diet.  Instead, we have to trick the body into doing something it wasn’t designed to do.  That’s the very opposite of “natural”.

The reason that medical progress in the diseases of old age has been so slow is that the researchers are all working with the wrong model.  They are stuck in the paradigm of the 20th century, when “natural medicine” was so successful.  The idea was to work with the body, to enhance the body’s natural defenses,  to help the body heal itself rather than to engineer fixes from the outside.

This worked really well for trauma and for infectious disease and all the diseases that young people get.  But it won’t work for the diseases associated with aging, because the body itself is the enemy.  The body is programmed to self-destruct—that’s the very essence of aging.  We can’t fix it by coddling or helping or restoring the body, because the body is divided against itself.  We can’t oppose aging with “natural medicine” because aging itself is natural, designed into our life plan.

 

Why don’t anti-oxidants work?

Every cell in the body generates the energy it needs in hundreds of tiny factories called “mitochondria”.  And it’s true that they generate toxic waste, in the form of ROS, Reactive Oxygen Species aka Free Radicals.  The ROS can attack the body’s sensitive biomolecules and make them dysfunctional.  This much is true, and it has been the basis of one of the oldest and most popular theories, the Free Radical Theory of Aging.

The Free Radical Theory is more than fifty years old, and based on the theory, a substantial industry of anti-oxidant vitamins and supplements has grown up.  If damage from oxidation was the problem, then anti-oxidants should be the solution.  It was a plausible theory when it first came out, but we’ve known for twenty years now that anti-oxidants don’t work.  The only reason this news hasn’t reached the public is that it is bad for sales.  What is more, we now understand why they don’t work.  It turns out that the damage caused by free radicals is completely avoidable, and it occurs when the body dials down its own native anti-oxidant system.  The body has its own anti-oxidants, perfectly adequate to quench the free radicals and keep the damage to levels at which it doesn’t accumulate at all.  Some of these molecules are glutathione, ubiquinone (aka CoQ10), and SOD=superoxide dismutase.  But they are all held back, so we have less of them in old age.  Our defenses against oxidation are crippled by design, and that’s why oxidative damge tends to accumulate.

The deeper reason why anti-oxidants do more harm than good is that the body uses free radicals as a signal that switches on active repair and rebuilding.  Every time you exercise, you generate copious free radicals, and they signal the body to repair damage, and rebuild muscle and bone better-than-new.  Free radicals also signal the body to keep insulin sensitivity high, steering away from diabetes.  When we take anti-oxidants, we interfere with this system, and that’s why anti-oxidants do more harm than good.  Anti-oxidants shut off the signal that tells the body to rebuild tissues and upgrade defenses.

 

Hormesis

It’s an idea with enduring appeal, that the reason we age and die has to do with accumulating  toxins.  And modern life is toxin city—pesticides, fertilizers, plastics, GMOs, and heavy metals.  But, once again, the idea has not panned out.  It is based on a faulty foundation,  a mistaken concept of aging and where it comes from.

Tiny doses of toxins may, in fact, be good for us.  Homeopaths have been telling us this for 200 years, but only in the last decade has hormesis gained acceptance as a medical concept.  Confronted with a challenge, the body jumps to respond, and unexpectedly, the body over-reacts.  We are stronger and live longer in the face of hardships than if we live a protected life.  Dogs exposed to tiny doses of chloroform live longer than dogs that are fed a pure, toxin-free diet.  Rats raised in a germ-free environment don’t live as long as rats who get an average dose of dirt and disease.  And so on…there is a whole literature of hormesis.

 

Paleo diet

This is an idea based on a completely muddled understanding of aging.  But despite this, it happens that it’s not a bad diet.  The Paleo Diet is one of those ideas that works much better in practice than in theory.

Grains are mostly starch, and avoiding starch offers a substantial benefit.  Starch is turned instantly to sugar in the mouth, before it even reaches the stomach.  Less starch and sugar means less insulin, which slows the decline into insulin resistant “type II” diabetes, which is one deep cause of aging.  Raw foods are a good idea precisely because they are difficult to digest.  Raw foods are absorbed slowly and incompletely.  For those of us who enjoy eating or who are addicted to food, raw foods may allow us to eat to satiety, because more of the food goes through us, and less is absorbed.  Raw foods are also less prone to cause a spike in blood sugar, triggering insulin release.

Just try getting fat on a raw food diet, and you’ll see what I mean.

Less starch and more raw foods are the best things about the Paleo Diet.  The theory behind the Paleo Diet is something else again.  It’s based on the idea that our body is evolved to work with the foods that were available while we were evolving, which was, for the most part, before agriculture, in hunter-gatherer societies.  You might be suspicious from the get-go when you realize that life expectancy in hunter-gatherer societies is under 40 years, even when the high rates of infant mortality are factored out.  If the paleo diet worked so well, we would expect to find some extraordinarily old people among native peoples in parts of South America and Borneo where they still live the lives of our ancestors 20,000 years ago.

 

What works?

There is a lot you can do here and now to slow aging and improve your odds for continued good health.  I’ve summarized what I know on the page AgingAdvice.org (a non-commercial web page with no advertising).  If you adopt all these measures, it should buy you an extra decade of health.  Much of it is standard medical advice:

  • weight loss
  • vigorous exercise
  • daily baby aspirin
  • a low-carb, anti-inflammatory diet
  • regular sleep habits

But there may be more effective and easier remedies available soon.  The future of anti-aging medicine is fast upon us.

The good news is that researchers are beginning to realize that aging is an inside job.  There are hormones and biochemical signals that tell the body to self-destruct.  Jamming a chemical signal is something that pharmaceutical companies know well how to do and it’s much, much easier than repairing a body full of random damage.  Some of the hormonal signals have been identified just in the last year or three:  Pro-aging (inflammatory) signals have names like NFκB and TGF-β.   Anti-aging signals include GDF11, melatonin, and the “love hormone” oxytocin.  Researchers at Stanford are beginning this month to test transfusions of blood plasma containing a hormone mix from young donors as a treatment for Alzheimer’s Disease in the elderly.

Telomere regrowth is another area that has the potential to extend life dramatically, and even to roll back the years.  There are several companies now selling herbal supplements that can turn on telomerase modestly.  Researchers are hot on the heels of powerful telomerase activators that might actually turn back the body’s primary aging clock.

Look for tangible progress in anti-aging technologies in the near term.

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* One is glucophage=metformin; the other is deprenyl=selegiline=eldapryl=emsam.

 

17 thoughts on “Anti-aging Oxymorons and         Anti-oxi-morons

  1. If we have fewer endogenous antioxidants as we age, should we not consume them more as we age?

    As I am sure you know, antioxidants are not all created equal. It seems to me that fat-soluble antioxidants like lipoic acid, which I understand to raise glutathione levels, cannot be compared with water-soluble antioxidants such as various polyphenols or vitamin C. And of course, vitamins A and E can barely be considered antioxidants at all at reasonable doses.

    If NFkB is an pro-aging, would not inhibitors such as curcumin and silymarin be “anti-aging?”

    Thanks

  2. Regards Telomeres:
    while I’m not sure if the measurements are reflective of increases throughout, say stem cells, it has been claimed that a vegetarian diet combined with even modest low intensity exercise can increase the length of telomeres in humans by a noticeable amount.

    Regards Thymus:
    I’ve heard that some doses of melatonin are able to reverse thymic involution in nonhuman animals.

    Regards natural substances, we have to remember that some can interact with regulatory proteins and alter gene expression.

    For example I believe that CR is at least in part probably an artefact of metabolic regulatory networks and not a primarily evolved survival mechanism, it works up to around 65% restriction in some animals but requires optimal nutrition unlikely in any natural environment at that level of restriction. If you can mess directly with the signaling pathways there’s no telling what the limits are, as you wouldn’t be bound by minimum survival necessary caloric intake limits, and multiple substances are emerging that appear to affect the signalling directly such as nicotinamide riboside, and the various partial cr-mimetics(resveratrol, fisetin, pterostilbene,etc). There’s also probable dietary means of also activating these signaling pathways such as low methionine diets, which can be combined with the substances and probably yield additive effect.

    • Darian –

      I haven’t seen claims that a vegetarian diet can increase telomere length. It’s a hard measurement to make because there is so much variability from day to day, from year to year, from person to person. It would have to be a very large study. Can you give us a reference?

      Reversing thymic involution is difficult to sustain. I’ve heard it can be done short-term with temporary shots of growth hormone. There are troubling side effects of growth hormone.

      I believe CR is an evolved mechanism for population regulation. Think of it as aging extra fast when there is a temporary plentitude of food, so overpopulation is a risk. The idea that CR life extension only works with optimal nutrition has become part of the biological lore, but it has never really been tested. At the very least, there are big exceptions, as when insufficient protein and methionine help to ENHANCE life extension from CR.

      • The telomere study wasn’t large but iirc, it took measures after five years, which should give time for changes to accumulate, between comparison groups and had noticeable differences

        “The group that made the lifestyle changes experienced a “significant” increase in telomere length of approximately 10 percent. Further, the more people changed their behavior by adhering to the recommended lifestyle program, the more dramatic their improvements in telomere length, the scientists learned.

        By contrast, the men in the control group who were not asked to alter their lifestyle had measurably shorter telomeres – nearly 3 percent shorter – when the five-year study ended. Telomere length usually decreases over time.”-http://www.ucsf.edu/news/2013/09/108886/lifestyle-changes-may-lengthen-telomeres-measure-cell-aging

        “I believe CR is an evolved mechanism for population regulation. Think of it as aging extra fast when there is a temporary plentitude of food, so overpopulation is a risk. The idea that CR life extension only works with optimal nutrition has become part of the biological lore, but it has never really been tested. At the very least, there are big exceptions, as when insufficient protein and methionine help to ENHANCE life extension from CR.”

        While I don’t remember the source I’ve also heard it must be gradually undertaken or else no lifespan benefits are seen if it is introduced all of a sudden in adult organisms, in nature it seems sudden famine is more likely. Also it seems to work up to about 65% in some animals, even if we were to assume no supplementation is necessary in more mild calorie restriction, it is unlikely there wouldn’t be serious malnutrition at such extreme levels, yet it keeps on working past what would seem like natural environment nutrient limits.
        Regards methionine, iirc, it’s believed to be one of the key signals of nutrient availability which is used by the mechanisms of cr, but it cannot be reduced beyond a certain point without severe side effects.

        As for testing malnutrition CR I would imagine you consider CR not effective in humans or else some of the poorest on earth would be breaking records, which they’re not and would serve as a test if it is effective in humans.

        • Thanks for the reference to the UCSF study. The actual article is here. I’m all in favor of these life style changes, and I think the research shows great promise, but we know it will never be a cure for aging because there are already many people pursuing the healthier life style. Keep in mind that the “pilot study” had just 10 test subjects, all male, and that differences between test and control were barely statistically significant.

          CR in humans is effective, but only adds a few years. In longer-lived animals, CR adds proportionately less to life span. But it seems to work even when nutrition is incomplete. Amsterdam experienced food shortages during the Nazi occupation years, and mortality and hospital admissions went way down.

  3. “At the very least, there are big exceptions, as when insufficient protein and methionine help to ENHANCE life extension from CR.”

    Forgot to add, iirc, those were studies trying to find out if cr required restriction of all macronutrients or just one, it was found protein intake was the critical nutrient, later they searched if all amino acids were critical or if there were one or more that was the primary signaling nutrient.

    So it was found that methionine was the critical ingredient within protein. Amino acids I’ve heard affects mtor activity and this may be one of the mechanism by which nutrient availability is sensed using protein intake. Whether methionine has a stronger effect than other amino acids, I’m not sure, could be it’s primary effect is through some other area.

    “CR in humans is effective, but only adds a few years. In longer-lived animals, CR adds proportionately less to life span. ”

    CR in animals increases lifespan proportional to the degree of restriction, in longer lived animals like dogs I’ve heard about 16% increase based on 25% restriction, doesn’t seem like much reduction especially given smaller group size which may result in no animal reaching the maximum potential as opposed to large rodent studies, but also unlike rodents that have been tested en masse for decades, we don’t know if their baseline 100% is equivalent to rodent 100% for all we know dogs might tend to eat less liberally then rodents if left to their own devices.

    Going from yeast, to insect, to mice the magnitude of the increases seem similar, and even in dogs it also seems similar.bIt remains to be seen whether the benefits in humans would reduce all the way down to single percent increases.

    “Amsterdam experienced food shortages during the Nazi occupation years, and mortality and hospital admissions went way down.”

    we would have to see how severe the shortages were, it is doubtful that most of the population was experiencing 50-60% restriction. In any case, iirc, sudden large drop in caloric intake on adult animals seems to abolish benefits, so at most it was moderate or slight restriction that was accomplished briefly.

  4. Forgot to add:
    “Keep in mind that the “pilot study” had just 10 test subjects, all male, and that differences between test and control were barely statistically significant.”

    Well prior study had shown increased telomerase activity in subjects, this was only to preliminarily confirm long term effects.

    ” but we know it will never be a cure for aging because there are already many people pursuing the healthier life style. ”

    They would have to keep the lifestyle indefinitely, and likely supplement with things like b12. Also those with too vigorous an exercise regimen, might get heart scarring, while those with too little exercise might not see enough benefits. How many elderly have both perfect diets as well as exercise regimens? While it might not cure aging, it is likely that those who don’t drop exercise and diet quality and remain true even in their later years could probably see some benefits.

  5. Hi Josh, great website you have, one of the best aging websites I ever saw. Independently of you I came also to the conclusion that aging is nothing more than a programmed selfdestruction process from the body itself. I am also of the believe that researchers have all until now been working with a completely wrong model and that this is the reason why we haven’t seen much real progress to address and solve the aging problem.

    I agree with almost all what you write but on one thing I have a different opinon and that is when you consider telomers to be the body’s primary aging clock. I believe telomere shortening is a consequence of aging rather than the cause of aging. I saw evidence of this but I don’t remember where I saw it. As a result of my research on aging at the internet I am now 100% convinced that aging is not only programmed but also centrally controlled from within the brain. I am also convinced that the hypothalamus is the place where all the signaling is done to steer the aging process. In my opinion all aging research should therefore be concentrated at the hypothalamus.

    • I am aware of some interventions to the pituitary that extend life span. The pituitary gland is part of the epithalamus, not the same as the hypothalamus, but close by.

      If you have studies linking hypothalamus to aging in mammals, I’d like to see them.

  6. Hi, you mentioned hormesis and how tiny doses of toxins and poisons might be good. If humans evolved various properties of hormesis for toxins and poisons, then only tiny doses of those toxins and poisons might be good, based on a natural selection argument.

    There could be many novel toxins, or old toxins in different amounts or patterns, where hormesis wouldn’t apply (e.g. mercury and some of those nerve agents). Your example of pathogenic microorganisms would fit in well with being an old toxin.

    So, it might still be useful to avoid some types of substances, even in small amounts.

    • WebMD says: “iron in their body can build up to dangerous levels. That excess iron can deposit in organs such as the liver, heart, and pancreas, which can lead to conditions like cirrhosis, heart failure, and diabetes.” Though they offer this warning only for people with genetic abnormalities, “Unlike some supplements, when the subject is iron, more is definitely not better. Adults shouldn’t take any more than 45 mg of iron a day unless they are being treated with iron under close medical supervision.”

      I haven’t seen excess iron related to the rate of aging in humans, but it is a risk factor for some diseases. LEF Magazine ran an aggressive article a few years ago warning against excess iron.

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