More About mTOR and AMPK

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by Nils Osmar. July 26, 2022. Medical disclaimer

An issue that keeps circling around in the life extension community is the question of mTOR, AMPK and longevity.

In one sense there’s no disagreement. Many studies have shown that too much mTOR activity (which corresponds with the under-activation of a different metabolic pathway, AMPK) can accelerate aging. 

Activating AMPK while decreasing the activation of mTOR has been shown to increase the lifespan in many different species, including mice, yeast, worms and flies.  Harvard researcher David Sinclair has spoken repeatedly about the dangers of over-activating mTOR and under-activating AMPK.

But jumping from this knowledge to concluding that we anything that might raise mTOR is bad for health and longevity strikes me as an oversimplification, and one which has been distorted by the current push in the mainstream media to portray plant based foods as “good for us” than and animal-based foods as “unhealthy”.

We appear to have evolved eating both animal based and plant based foods, and it’s likely that we have a need for both.

Benefits of mTOR activation

  • mTOR supports muscle growth and a strong immune system. Too little mTOR activity can slow and disrupt healing.
  • Too little mTOR contributes to diabetes and insulin resistance.
  • Too little mTOR can cause specific health problems such as cataracts in mouse models.
  • Lowering our mTOR too much — by, for example, severely restricting protein — can (if we go too far with it) result in muscle wasting and an immune system that leaves us vulnerable to infection, particularly in elderly people.

Too much mTOR activation

  • The over-activation of mTOR is associated with a number of disease conditions, including cancer, type 2 diabetes, obesity, depression, neuro-degeneration, and the aging process itself.
  • Activating mTOR is like starting a fire: fire can be used to warm our homes and heat food, but if it gets out of control it can burn us and burn our homes to the ground.
  • See article: mTOR is a key modulator of ageing and age-related disease

Benefits of AMPK activation

  • AMPK is the longevity pathway. In lab animals, when it’s activated, the result (assuming the animals are protected from disease) is a dramatically extended lifespan.
  • Fasting activates AMPK. This is, or appears to be, one of the reasons that animals which are fasted live so much longer than those that are not.

Controlling mTOR through diet

One way of lowering mTOR is to eat a plant-based diet. There’s no question that it works (as long as we don’t consume too many high glycemic plant foods such as grains and fruit).

But a plant-based approach is not always a direct path to health.

I was completely plant-based, i.e., vegan, myself for almost three years, carefully balancing my foods to make sure I was getting enough complete proteins, vitamins and minerals without eating any food from animal sources.

I was hoping this would improve my health, but it didn’t. There were some initial benefits, including increased autophagy, but as time went by I experienced several health problems, including memory and mood issues and issues with my eyesight and my teeth. All of these problems cleared up almost overnight when I added eggs, dairy and meat back into my diet. 

I’ve also seen similar declines in friends of mine who gave up animal based foods thinking it would improve their health. Two of them experienced a rapid progression toward frailty, memory problems, and dementia. One got rail-thin and started losing her hair and having tooth problems, then later became morbidly obese.

Plant-based diets can have adequate protein if they’re well planned. But the protein from plants tends to be lower in quality and bioavailability than the protein from meat and other animal sources. David Sinclair has acknowledged this, but claims that this is a good thing; eating low-nutrient foods, in his opinion, makes the body work harder to get the nutrients it needs for survival. I can just reiterate that there are dangers in this approach. I’ve known many people who experienced what I did when eating both vegan and overly plant-based diets.

Meat-based diet

Meat-based diets are the opposite: They’re rich in bioavailable nutrients. Of course, they can also be unhealthy if the meat if from factory farms and is contaminated, from its feed or its processing after the animal’s slaughgter, with synthetic hormones and pollutants.

When I went vegan, then went omnivore again, the meat I added back into my diet was from grass-fed animals raised on small family farms. For both ethical and health reasons I would not eat, or recommend eating, meat from factory farms.

Circling back to the main problem — if you eat a lot of meat without doing any fasting, your mTOR will be constantly activated. This may improve your immediate health and muscle growth may also be shortening your life.

Can we eat meat and still lower mTOR?

For those who want to include meat in their diets yet lower mTOR activation and increase the activation of AMPK, we can do so by balancing meat with a variety of plant-based foods, or by increasing our fasting. mTOR goes up when they’re eating; AMPK goes up when we’re fasting or eating lower protein, lower mTOR plant-based diets.

My diet

My current diet includes both plant-based and animal based foods.

Some plant-based foods I eat include:

  • Broccoli.
  • Cabbage.
  • Parsley.
  • Celery.
  • Cucumbers.
  • Mushrooms.
  • Red onions.
  • Garlic.
  • Tomatoes and cherry tomatoes.
  • Apples (in small amounts).
  • Pomegranate arils.
  • Dark chocolate.
  • Blueberries.

Some animal-based foods I eat include:

  • Pastured eggs
  • Wild sockeye salmon roe
  • Sardines (including bones) (in olive oil).
  • Wild Pacific salmon.
  • Organic free-range poultry.
  • Chicken hearts.
  • Chicken liver.
  • Organic grass-fed beef
  • Organic grass-fed beef heart and liver.

Vegan and carnivore days

Now and then I’ll do a carnivore day (no plants at all). When I do, I limit my feeding “window” to four hours, and fast for the other twenty. This cycles me between high mTOR activity when I’m eating and low mTOR/AMPK activation the rest of the time.

I also sometimes do vegan days in which I eat no animal-sourced food at all, and do five-day fasts and fasting-mimicking diets in which I eat less than 15 grams of protein for a few days, which both lowers mTOR and cranks up autophagy and apoptosis.

Finding the right balance

One side effect of the anti-mTOR tendency in the anti-aging community is that some people have become afraid of exercising due to a fear of activating mTOR. Doug McGuff addresses these (misguided) concerns in this video.

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