Growth & Aging; Creatine & Health

Prologue

Promoting growth is dangerous, especially if it is done in an un-natural way.

Hormones and growth signals are tightly constrained, and highly optimized by evolution.  Too little and the body atrophies over time, failing to renew muscle and nerve tissues.  But too much and the body risks overstimulating some rogue cell, which may turn cancerous.  Navigating between these two risks is a treacherous game, and the channel of safety is narrow.  Eventually, the body falls to one side or the other, and so we must die.”*

I have read this narrative in different contexts and in countless variations.  It is the central rationale of aging according to the mainstream of Western medicine.  But we know it cannot be true.  When we are infants, every endocrine growth signal is dialed up to the max, growth hormone is through the roof, cells are dividing like crazy, and yet cancer risk is very low.  When we are old, growth hormone has dropped to nearly undetectable levels, cell division is lethargic, stem cells are few and less active–and yet the risk of cancer is at an all-time high.

Mainstream evolutionary theory says that the body is forced to make compromises, and this this is the ultimate reason for aging.  The body doesn’t want to fall apart, but its first priority is to leave as many offspring as possible in the here and now, secondarily to preserve the body to continue to create offspring later on.  Here-and-now is safer and also more effective, because of the earlier start generating grandchildren.  So the body errs on the side of short-changing the infrastructure.  

Why should the body have to compromise?  The most popular and most standard theoretical answer is that its energy is limited.  There just aren’t enough calories to do everything perfectly.  This is the Disposable Soma theory of Tom Kirkwood, a beautiful theory that fails spectacularly when confronted with the real world.  In theory, more energy should help the body avoid the need for compromise.  We should live longer the more we eat.  The truth is the opposite.  In theory, spending energy on exercise should generate damage that needs repair, while consuming energy that could have been spent to protect from old age.  Theory says that exercise should shorten life span, but the truth, again, is just the opposite.

Even if energy isn’t the limiting factor, it sounds so reasonable that the body should be forced to compromise because we so often encounter tradeoffs in different areas of our lives.  Tradeoffs involve time and money, can’t be in two places at once, can’t have children and a career, must choose between two lovers who each fulfill parts of us.  But it doesn’t always work this way.  Computers become smaller and faster and cheaper and more energy efficient with each passing year.  Filling our lives with love and fulfillment and a sense of gratitude and wellbeing also is the best single thing we can do to enhance our life expectancies.  Sometimes you can have your cake and eat it, too; compromise isn’t always required.

So the question whether enforced compromises are implicated in aging must be answered by experiment and observation–it is not a matter of theory.  

The root of the theoretical problem is the assumption that the body is doing its best to live as long as possible, and that aging and death represent failures of a system trying heroically to avoid them.  But in this case, evolutionary theory leads us astray: the body is trying to kill it self on a schedule, as it is programmed to do.

The truth is that the body knows how to be young, and it knows how to be old.  It does an exemplary job of both, each in turn.  When the body is young, it is perfectly capable of growing, healing, producing offspring and repairing molecular damage, all accomplished simultaneously and without compromise.  When it is old, it does all of these things imperfectly, if at all, as it gradually degrades and dismembers itself, using some of the same tools that were deployed for health and protection early in life: immunity, inflammation, apoptosis and cell senescence.  

This view leaves open the possibility that medical science may find the body’s epigenetic clock, may learn how to talk to the body in its own language and fool it into thinking it is forever young.

So I am motivated to leave theory behind and look to the lab experiments for the answer:  is it possible to boost growth and simultaneously to enhance longevity?

 

Creatine

Creatine is a very simple and common molecule with nitrogen and a COOH group like an amino acid.  It occurs in all animal cells, more not plants.  1% of our blood is creatine.  Biochemistry of creatine has been studied since 1832.

Creatine promotes creation of ATP, the cell’s short-term energy storage molecule.  The way it works is this:  ATP is adenosine triphosphate, and the 3 phosphates make it a high-energy molecule.  In muscles and neurons that consume energy intensely, ATP is tapped, and one of the phosphates is degraded in the process, leaving ADP, or adenosine diphosphate.  Creatine then steps in to recharge ADP back to ATP.  It takes on a phosphate to become phosphocreatine, and then transfers the phosphate to ADP which is restored to its high-energy form, ATP.  In times of rest, the process is reversed, as ATP gives up a phosphate to creatine, and an enzyme called creatine kinase generates phosphocreatine.  Phosphocreatine can then serve as a short-term energy reservoir.

At any given time, there is something in the neighborhood of 100g creatine in our bodies.  The amount varies widely.  We make our own creatine in the kidneys and liver.  But a substantial portion of our creatine is ingested, except that those of us who eat a plant-based diet get very little creatine. “Normal reference values for creatine are lower in vegetarians [ref]”  We make less as we grow older, but it’s easy to lose the difference because of wide natural variation in creatine levels at all ages [ref].  

Creatine was first discovered to improve athletic performance in 1912.  Since stories emerged from the 1992 Olympics, creatine has been an increasingly popular supplement among body-builders.  Creatine works especially well In combination with exercise, enhancing the benefit for strength and lean muscle mass.  I found one study demonstrating these benefits in older men.  I personally have been experimenting with creatine the past 5 months, and have noticed I can do more push-ups and chin-ups, and have gained a few pounds that I flatter myself to imagine are muscle.  I have had a minor issue with cramping which might be a side-effect

But it is only since 2010 that creatine has been known as an inhibitor of myostatin (aka GDF-8).  Myostatin is a hormone that increases with age and degrades tissues, especially muscle tissues.   Inhibiting myostatin leads to more strength and muscle mass, including a stronger heart.  The action is not through more activity of muscle satellite (stem) cells, but of less wasting [ref].  

Myostatin also promotes resting levels of growth hormone while suppressing spikes of growth hormone during exercise.  This is generally thought to be a good thing, but the reasoning is indirect.  

The best effect might be the increase in muscle satellite (stem) cells, but evidence is still thin [ref], and the effect may be temporary [ref].  There is limited evidence for creatine’s benefit to cognitive performance, especially in vegetarians and the elderly [another ref].  It has been mentioned in the context of treating Parkinson’s Disease.  One study showed a decrease in the inflammation that comes after intense exercise.  

 

The Bottom Line

100% of people in their 60’s and beyond develop sarcopenia=loss of muscle strength.  No one likes it, and (if you need a clinical reason) sarcopenia increases risk of injury and very gradually closes the door to a world of benefits that derive from exercise.  Exercise itself is the best way to slow sarcopenia, and creatine synergizes with exercise to help in maintaining muscle mass, strength and endurance.

Strengthening the heart is likely to be a good thing, and I have a belief that endurance and motivation and exercise and longevity are all so closely linked that I’m inclined to think there are ripple benefits from creatine. Some studies show that effects fade, so I’ll  take it intermittently, one month on, a few months off.  Drink much extra water while you’re taking creatine.

Long-term effects of creatine supplementation in humans have not been studied, except for one safety study that lasted a year and found no adverse side-effects and a small 4-year study that looked at a limited number of biomarkers.

You can purchase creatine as a powder, and it is not expensive.  It is tasteless, and can be added to drinks (but not OJ), yoghurt, or smoothies.  There is no consensus on dosage.  I have seen recommendations ranging from 1 to 20 g per day.  

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* Not a literal quote from anywhere, but I place this introduction in quotes just as a warning that I don’t believe it, and I don’t wish you to believe it.

17 thoughts on “Growth & Aging; Creatine & Health

  1. Josh, Thanks for this simple easy to understand exposition on creatine..I wlll read the links…I will especially read through the report that the affect of creatine fades after a while..But you seem to have synthesized all the information very well..

    I have been taking a teaspoon a day for the past 3 weeks as part of my anti-aging program…And I too am a vegetarian…

  2. A way to (somewhat) reconcile the “common sense” of Disposable Soma with ‘Programmed’ aging would be to suggest the trade off had to be made *by* evolution, in a calorie restricted environment.

    Now that the program is in place (set by this process), more calories would only exacerbate the side of the hill one is falling off. (cancer / decay)

    • I’ve often seen the claim that food is short in natural environments through most of evolutionary history. No evidence is offered–it’s just supposed to accord with general experience. But I think it’s just as likely that natural environments are very variable, and that both famine and abundance are common, perhaps in alternation.

      • Oh Josh, we hear these ‘brilliant’ observations from the ‘Evolutionists’ about how traits exhibited at old age can have little selective pressure (except that cancer is always the exception, as in that quote above’s reference to ‘rogue cells’), how old age doesn’t occur in Nature and how Nature deals with limited ‘energy’ by aging. All the same sort of commonsense, obviously correct observations that were nothing of the sort. All untested assumptions made by those who KNOW. We call this phenomenon ‘arrogance’.

  3. Josh I have just checked the limited evidence for creatine’s benefit to cognitive performance in vegetarians. It says that in young adult female “vegetarians rather than in those who consume meat, creatine supplementation resulted in better memory. Irrespective of dietary style, ” Having read this I wonder if there is any research around studying the effect of creatine on older vegetarians..

    • Makes you think that vegetarianism decreases memory by a mechanism that creatine can counter. I wonder if meat too would result in an improvement?

      • Ahhh yes, I agree it possibly would. I wonder if there is evidence out there for this ? But all of us are creatures of long standing dietary habits..Such is the case with me being vegetarian..And probably many other folks..

        The evidence in Josh’s report is that creatine helps all of us with slowing aging But it has even more value to vegetarians as part of the anti-aging program..And that is good & useful to know.

  4. Thanks for a very informative blog!

    As a layperson I can’t help to think that whatever attempt we make to increase lifespan, death will eventually win. As you have mentioned time and time again, aging is basically programmed death. We can try to re-program death schedule with telomerase activators. Add supplements like resveratrol, MitoQ and the list goes on.. We can manipulate with mTor, SIRT(X), at least to a certain extent, but death will win….eventually. We inhibit inflammation with curcumin, resveratrol EGCF, but still some 24.000 genes will come into play to secure evolution. Genes, which science has yet to discover and understand the full purpose of. Genes, which may not play a role for longevity today, but may play a role in the future as part of evolution. The question is: Do we really have a chance to expand life further than a handfull of years? Can we really cheat evolution? And yes, I agree that we’ve had enough “in-vitro” theories that fall, once implemented in practise. My own anti-aging regimen includes intermittent fasting, vigorous exercise and a limited number of supplements taht are well-documented.

    • I believe such experiments are part of the evolution. Generally speaking longevity evolved whenever a species was able to create a stable environment for itself (reduced danger of famine, illness, predation etc).
      In that respect humankind is magnitudes better than any contemporary living species. No other species comes even close to the chances of a human offspring to live through reproductive years. In that respect we could live magnitudes longer, maybe 10x -100x.

  5. There is (at least one) child with a mutation so he produces little or no myostatin. He was unusually muscular for his young age.

    It would be interesting to follow his story to see how he grows up and ages.

  6. Adenosine triphosphate (ATP) is produced in the mitochondria. It is a little too big to pass through the mitochondrial cell wall and into the cytoplasm of the host cell. Creatine is small enough to pass through the mitochondrial cell wall. Creatine enters the mitochondria and an ATP molecule passes a phosphate group to Creatine forming Creatine phosphate (a high-energy compound) and leaving a molecule of ADP to be rephosphorolated by the mitochondrium. Then the Creatine phosphate passes through the cell wall of the mitochondrium and into the cytoplasm. There the Creatine phosphate passes it’s high-energy phosphate group to ADP forming ATP. Without Creatine, the mitochondria would not be able to provide ATP to the cell to power the cellular functions.
    Creatine is believed to inhibit myostatin; but maybe it is actually an abundance of ATP that inhibits myostatin? Myostatin is a mystery in it’s self. Why do we have myostatin, just to kill us in our old age?

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