Balancing the Activation of mTOR and AMPK

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by Nils Osmar. Updated Feb. 11, 2022

AMPK and mTOR are two metabolic pathways at the heart of our metabolism.  When one is switched “on” the other tends to be “off.” AMPK activation is associated with an unusually long lifespan – mTOR, with the growth of skeletal muscle and with a robust immune response.

AMPK and mTOR in a Nutshell

  • AMPK is the longevity pathway. It’s considered to be catabolic because of its association with autophagy and the recycling of nutrients and body tissues. Current research suggests that if we want to live long lives, AMPK should be activated most of the time.
  • mTOR is the growth pathway. It’s considered to be anabolic because of its association with muscle growth and repair, and the proper functioning of the immune system. Research suggests it should be activated periodically just enough, and just often enough, to support muscle growth and immune health.
  • Muscle growth is good, but we don’t want all of our life energy to go into growth at the expense of longevity. .
  • I like visualizing AMPK and mTOR as two ends of a teeter totter. If one goes up, the other (usually) goes down. 

Both are Necessary

We need some mTOR activation to maintain and build muscle mass as we age, prevent sarcopenia, and support our immune systems. But hundreds of animal studies have shown that animals of all species live longer if AMPK is activated most of the time. 

How to Activate AMPK

AMPK can be activated by:

  • Fasting.
  • Exercising.
  • Eating meals low in protein.
  • Eating meals low in leucine.
  • Eating plant-based foods, which tend to be both low in protein and very low in leucine.
  • Taking cold showers or baths (or keeping the house temperature in the low 60s).
  • Taking supplements and medications such as berberine, metformin, benfotiamine, milk thistle and rapamycin. (This doesn’t mean we need to take all of these compounds at the same time or take them every day. But they can be useful to be aware of if your goal is to speed up or intensify the activation of the AMPK pathway.)

How to Activate mTOR

mTOR can be activated by:

  • Eating meals high in protein.
  • Eating foods high in leucine, such as fish, some types of nuts and seeds, red meat and organ meats.
  • Taking supplements such as branched-chain amino acids, which contain leucine and isoleucine.
  • Eating a lot of carbohydrates, particularly ones that raise blood glucose and trigger an increase in insulin. (Note: A danger of activating mTOR with carbs is that high blood glucose and insulin can have devastating effects on our health.)

Switching Back and Forth

One way to keep AMPK activation high and mTOR activation low would be to eat a vegetarian (or low-protein Mediterranean) diet, as David Sinclair and some other folks in the anti-aging community recommend.

An alternative approach would be to alternate between eating foods high in protein and leucine, and bouts of fasting or eating almost zero protein.

The latter method has some adherents. In his book called “The Switch,” James Clement recommends 8 months of AMPK activation (in which the person would eat a mostly plant-based diet) followed by 4 months of mTOR activation (in which more animal-based foods would be eaten). But AMPK and mTOR can also be switched on and off on a daily basis.

My Approach

My goal is to have AMPK “on” about 75 to 80 percent of the time, and mTOR “on” for the other 20 to 25 percent.

According to Dr. Rhonda Patrick, the best time activate mTOR appears to be shortly after a workout (resistance training. In accordance with this principle, I work out three days a week and time my mTOR activation to take place within an hour or so after my workouts.

I do this by eating high protein, animal-based foods such as eggs, fish and meat, all of which are rich in leucine shortly after the end of a bout of resistance training.

Am I in danger of too much mTOR activation (and too little AMPK)? I don’t think so, because I always either fast or eat very low protein meals on the day before working out. On my pre-workout days, I either:

  • Eat nothing (no food for either 24 or 36 hours)
  • Eat just one meal (i.e., skipping breakfast and lunch and just fasting until dinner)
  • Alternatively, I might sometimes do a sort of one-day “fasting mimicking diet” which has almost zero protein and almost no carbs (such as having a tomato/avocado smoothie in the morning and afternoon, and no other food)

My Current Protocol

My diet and exercise regimens are part of a larger protocol aimed at reversing aging and rekindling health and longevity pathways:

I start by doing a low-protein day or a total fast on the day before working out. Then on my workout days I might wake up around 5 or 6 a.m.; have some white tea or coffee (which helps activate the AMPK pathway); get some work done; then work out fasted from 9 a.m. till 10:30 a.m.; then have a high protein, high leucine breakfast around noon.

As shown in the graphic below, my AMPK (blue) is activated about 80 percent of the time; my mTOR activation (shown in red) is brief and is timed to occur right after exercising. That way the mTOR which is activated will be driven into the muscles to start the process of repair, will be put to good use, and will not have a pro-aging effect.

When we eat protein in the short window of time following a workout, the mTOR activation takes place in our muscles, where it can provide benefits, not elsewhere in the body where it could do harm. (Recent studies have established that mTOR activation (from eating leucine) lasts for 2-3 hours.)

The graphic above shows my mTOR activation (in red) averaged over a week. The upper image is mainly blue, because my mTOR is only being activated for 2-3 hours per day. The graphic below it shows mTOR activation in a typical American diet in which people are nibbling on protein and carbohydrates all day.

As the image above shows, this approach lets me eat high protein meals (after workouts) while still keeping my AMPK activated most of the time.

  • If I were eating high protein every day, I could still make this work, but I’d need to be doing more fasting. (For example, I might skip breakfast and compress my eating within a 6-8 hour window per day.) This would give me some autophagy and AMPK activation in the mornings. Because I fast 72-80 hours a week, I usually go ahead and eat three meals on my eating days.
  • The chart below shows how most Americans are in an mTOR state (red) most of the time (AMPK is blue).

Activating Our Anti-Aging Genes with Hormetics

  • Hormetics are stressors that benefit the body by putting us into a state of mild (and temporary) stress.
  • There’s strong evidence that hormetic stressors benefit us by activating our sirtuin (lonvegity) genes. Heat and cold are exposure are examples.
  • Things which activate AMPK also tend to switch on our anti-aging genes. Keeping the house cool (65 degrees or less) or taking cold showers can activate cold shock proteins; taking saunas or hot baths can switch on heat shock proteins. I take contrast showers (alternating between hot and cold, ending on several minutes of cold) three days a week.

Photo Credit: Image by Colin Behrens from Pixabay

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