AMPK Supports Longevity. mTOR Supports Strong Muscles and Immunity. Here’s One Possible Way to Balance Them

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by Nils Osmar. Updated Nov. 21, 2023. Medical Disclaimer

AMPK and mTOR are key enzymatic processes which are essential to our health and well-being. One way to visualize them is like a teeter totter. When one is “on” (or up) the other is usually “0ff” (or down.

Why it matters

  • AMPK supports longevity. Researchers refer to it as “the longevity pathway”.
  • mTOR supports muscle growth and a strong immune response. It’s protective against sarcopenia.
  • Both pathways are important, but evidence from animal studies suggests if our goal is to extend lifespan, it may be beneficial to should have AMPK “on” (and mTOR “off”) most of the time.

Switching on AMPK

Interventions which suppress mTOR tends to switch on AMPK. The drug rapaymycin is an example. (The word “mTOR” stands for “mammalian target of rapamycin”). Rapamycin dampens the activation of mTOR and has been shown to have dramatic life extending effects in many lab animals.

We don’t need drugs, though, to turn off mTOR and turn on AMPK. AMPK becomes activated at night when we’re sleeping, though it may take a few hours for it to come on fully if we eat a huge meal right before bed.

Anything which triggers the release of insulin will also turn on mTOR. So both protein and carbohydrates can activate it. Animal-based meals that are rich in the amino acid leucine are the most potent mTOR activators.

Meal timing matters

If we eat our last meal at 7 pm, mTOR will be activated. Depending on how much protein, carbohydrates and leucine was in it, it may take 2 or 3 hours for the mTOR activation to die down.

At some time during the night, the mTOR “fire” will burn out, and AMPK will come on again. We wake up in the morning with AMPK activated. AMPK will then stay on it till we eat our first meal. If we skip breakfast and don’t eat till noon or 1 pm, the effect will be extending our time spent with AMPK turned on.

This is one of the benefits of eating two meals a day. If we skip breakfast and lunch and just eat one meal a day, we’ll spend most of our day in AMPK.

David Sinclair takes it a step further, and eats only one meal a day. If his meal has a three hour window, this means that that he’s fasting 21 out of every 24 hours, for a total of 147 hours. His meal is largely plant-based. So he’s almost always in an AMPK state.

Taking fish oil (or eating fish)

Fish oil inhibits Interleukin-11 signaling (which in turn reduces pathogenic mTOR signaling)

  • Some mTOR signaling, particularly in the brain and muscles, is healthy and beneficial. See study
  • But the activation of mTOR elsewhere in the body (such as our fat cells) is not.
  • The pathogenic signaling of mTOR is associated with faster aging, and correlates with an age-related increase in Interleukin-11 signaling, and with greater inflammation.
  • This study found that taking fish oil inhibits Interleukin-11 signaling.
  • For those concerned about rancidity in some commercial fish oils, an alternative would be eating foods such as sardines, anchovies and wild Pacific salmon which are naturally high in fish oil
  • Related study

Too Much AMPK Activation?

I’ve tried different WOEs (ways of eating) in the past. For example, I was vegan for almost three years – avoiding leucine, and trying to keep my glycemic index low. This kept me in an AMPK state almost all the time.

There were some benefits at first. I lost weight and my energy improved. But within a few months, I started feeling exhausted. I first lost weight and got rail-thin, but then I developed insulin resistance and started putting on belly fat. (I ended up almost 100 pounds over my ideal weight.)

I lost muscle, started having mood swings, got poor eyesight, and developed memory problems. I also got sick a lot during my vegan years. I’d catch every cold and flu bug because my immune system was no longer working very well.

The truth is that I was activating AMPK too strongly. All of these problems went away once I added some animal-based foods back into my diet.

Some people may be able to thrive on vegan diets; I could not, no matter how many tweaks I made to the diet. I learned from this experience that I needed some animal protein to activate mTOR. It simply was not happening, regardless of how much plant-based protein I ate, when I was on a vegan diet.

Balancing mTOR and AMPK

There are 168 hours in a week. My goal is to have AMPK switched about 2/3 of the time. This still gives me lots of opportunities to activate mTOR.

What I’m doing

I’m currently working out with weights two or three days a week, and doing cardio, aerobics, Zone 2 and/or HIIT on three other days. I have one day when I don’t do either.

Dr. Rhonda Patrick has said that the “safest” time to activate mTOR is right after working out; this pushes the mTOR activation into our muscles and should prevent it from having a pro-aging impact on the body. To build muscle and maximize the benefits of mTOR activation while minimizing the possible pro-aging effects, I try to activate mTOR on my workout days an hour or so after working out.

My schedule

My schedule actually varies, in what I hope is a good way. Sometimes I just eat within a four hour or six hour window, regardless of the day of the week, keeping most meals animal-based. But if I really want to focus in on AMPK and mTOR activation, I’ll follow the regimen below.

  • MONDAYS – resistance training. I fast in the morning, for some AMPK activation; work out fasted (for more AMPK activation); then eat a high protein animal-based breakfast around noon or 1 pm. For example, I might eat several eat eggs scrambled in with sardines and oysters for breakfast, along with broccoli and tomatoes (which, eaten together, are anti-cancer). My later meal is also animal-based (for example, I might eat some beef, pork or chicken along with some carrots, onions, and garlic, and a small purple or white potato). The exercise is giving me some catabolism and autophagy; the meals are giving me some anabolism.
  • TUESDAYS –. I usually fast till about 4 or 5 pm, then have a high protein meal. (Since I haven’t eaten since the previous night, this would be about a 20-22 hour fast). But I sometimes decide to fast all day Tuesday and don’t eat till Wednesday around noon (a 36-40 hour fast) I may do some HIIT or Zone 2 or aerobics.
  • WEDNESDAYS – resistance training. Similar to Monday.
  • THURSDAYS – 8 hour eating window. I may do some HIIT or Zone 2 or aerobics.
  • FRIDAYS – resistance training. Similar to Monday
  • SATURDAYS – 8 hour eating window. I may do some HIIT or Zone 2 or aerobics.
  • SUNDAYS – No fasting or working out.
  • Now and then I’ll mix this up and only work out two days a week.

Other possible approaches

David Sinclair is a key figure in the anti-aging movement. He has recently shifted to eating just one meal a day, though he does say that he snacks on nuts and seeds during the day if he gets hungry. He’s not vegan, but eats “largely” plant based (and recently gave up red meat).

His approach appears to be based on keeping AMPK “on” constantly, keeping mTOR “off”, keeping IGF-1 (a human growth hormone) low, and avoiding animal-based foods as much as possible.

I can see the logic of his approach, and I wish him success with it. But for me, his approach would be too much AMPK activation and too little mTOR, and could in theory push my IGF-1 too low. James Clement, author of “The Switch” — a book about switching between AMPK and mTOR — is a strong advocate of activating AMPK, but has pointed out that if our mTOR is too low and our AMPK is too high, we’ll eventually start wasting away.

Sinclair’s approach appears to be focused on always keeping AMPK low. My approach (more similar to James Clement’s), is about cycling between AMPK and mTOR. Clement cycles from month to month; I cycle back and forth several times a week.

The IGF-1 Question

Eating animal-based foods can increase both mTOR and IGF-1. IGF-1 is a growth hormone. Increasing it could, in theory, shorten our lives.

But it’s important to be aware that IGF-1 can go too low, and there are serious dangers in allowing that to happen. According to this study, if IGF-1 goes too low, the result is brain atrophy, loss of grey matter and a greater risk of Alzheimer’s.

From the study:

Lower serum levels of IGF-1 are associated with an increased risk of developing AD dementia and higher levels with greater brain volumes even among middle-aged community-dwelling participants free of stroke and dementia. Higher levels of IGF-1 may protect against subclinical and clinical neurodegeneration.”

  • The phenomenon revealed in this study is one of the reasons that I like to cycle between periods of fasting (which lowers IGF-1) and periods of eating high protein meals which include some animal protein.
  • There’s no benefit (to my mind) in living longer if it’s at the expense of our brain health.
  • This page has more information about my current protocol: https://newlifelongevity.com/the-rekindle-protocol-a-blueprint-for-reversing-aging-and-living-longer/

Here’s an interesting discussion between Peter Attia and Rhonda Patrick which touches on this issue:

Could I be overactivating mTOR and IGF-1?

It’s possible. But I’m really don’t think so. The large amount of fasting I’m doing is keeping me “in AMPK” most of the time. The fasting is periodically lowering IGF-1. The high protein meals (on my exercise days) are making sure I have enough of both IGF-1 and mTOR activation.

I’m timing my IGF-1 and mTOR activation by eating high protein animal based foods primarily on my workout days. (I either fast or eat more plant-based on the other days.) It’s going into supporting muscle growth, which is what I want. I have zero interest in “unhealthy” life extension. I think I’m on the right track. Time will tell if I’m right.

Summing up

  • In a nutshell, I’m trying to strongly activate mTOR and IGF-1, but also strongly activate AMPK with exercise and fasting.
  • When I do eat, it’s usually a high=protein, animal-based meal (but also often includes some plants). (Some people refer to this as an animal-forward diet.)

My results

Anti-aging results can be difficult to measure. But some changes can be very visible. One tangible result of my cycling between AMPK and mTOR activation (by alternating between eating animal proteins and fasting) is that I’ve been able to gain muscle mass while simultaneously losing body fat.

The videos below show what I looked like in the fall of 2020 (left) and the spring of 2022 (right). I’m not saying that being able to put on some muscle proves that I’ll live longer; but that in the video on the left, I was drifting into sarcopenia; in the video on the right, I’ve been able to reverse it.

My A1C, cholesterol levels and other biomarkers have also all improved. I’ll be doing some epigenetic tests soon and will start posting those results here also when I do. My memory is better than it was in my vegan days, and my mind is sharp and clear. I’ve also been able to add muscle while reducing body fat, and improving all of the usual biomarkers.

My biomarkers

According to aging.ai v3, my biomarkers are those of a 41` or 42 year old man. (My youngest estimate from Aging.ai was 39). (This isn’t to say I look 40; but I’m often told I do look young for my age.) I’m 70 (almost 70), so I take this as a good sign.

Image by Iván Tamás from Pixabay

Not medical advice

This article is not intended as, and should not be taken as, medical advice. I’m not advising that people eat any particular diet or take any particular supplements, just reporting on what I’m doing. All supplements can have side effects; I would encourage people to research both possible benefits and side effects before starting on any supplementation regimen.  See full Medical Disclaimer

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3 Comments

  1. I’ve been a successful vegan for 2o years. Prior to that I ate one tin of sardines a week but I experienced no improvement to my health until going fully vegan. Rather, I was pudgy and lacked energy. I eat a variety whole grains, legumes, fruit and vegetables and limited amounts of nuts and seeds. I also supplement with vitamin B-12, D, and TMG. I also do HIIT and bodyweight exercise 3 times a week, ride a bicycle frequently and get a minimum of 7 hours sleep. I maintain a normal weight without effort and am decidedly on the muscular side. I typically go for half a dozen years without getting even a simple cold. Is it possible that your lack of success with veganism was due to missing something in your diet or lifestyle?

  2. Hi Paul,

    I can see why you might ask that, but the truth is, I spent three years trying to “fix” my vegan diet and sort out any nutrients that might have been “missing”. My health still kept going downhill.

    I read books by vegan authors, watched interviews, read articles about their protocols. I studied nutrition. I was motivated to try to make it work, so stuck with it for three years.

    But as time went by, regardless of how I tried to “fix” it to “make it work for me”, my health kept declining. It became apparent that the diet itself (in all of its variations) was the problem.

    Part of what made me realize that it was not just my issue was seeing other friends, some very young, who were also getting sick on a vegan diet. Some of them stopped being vegan and immediately, almost overnight, got better. Others did what you’re suggesting, and keep trying to “fix” their diets, and went on being sick for a long time.

    One friend who comes to mind was a woman in her 30s who had been vegan for over five years. Her health had been declining for a while. She ended up getting really sick. I drove her to a doctor, who told her she was malnourished and that she really should eat some meat. She wouldn’t to because it would be “violating her vegan diet.”

    She got sicker and sicker, still trying to stay vegan. She kept trying to tweak and “improve” her diet while staying vegan.

    Her hair started falling out. Her teeth started coming loose and one came out. Then at one point, she stopped menstruating, at the age of 33.

    She had a mentor of sorts who ran a “vegan support group”, and told her about the problem. Her mentor, who was a true believer (and batshit crazy) told her that she should be celebrating because she had “detoxed away her periods!” And should try “living like the banana girl!”

    What was actually happening, of course, was that her core health was failing because the nutrients in her diet were so low. She wasn’t menstruating because she was starving herself of the nutrients needed for to maintain a reproductive system. Oh, and her mentor said losing her teeth “was a form of detox” too.

    Not to say that everyone following a vegan diet goes sterile, or loses their teeth and hair, but that it did happen to her, and has happened to several people I knew in that community, regardless of how hard they try to “fix” their diets while staying vegan.

    She of course could have gone on for another few years as a vegan trying to fix it (and no doubt died young… it was where she was headed.) But she chose to say “screw it”, dropped out of the support group, and went back to eating meat. Within six weeks she was menstruating again. Two years later she was able to have a baby.

    In my own case, I spent three years trying to tweak my vegan diet to make it work. I finally realized, after seeing what had happened to her and some other friends, that the problem was veganism.

    If someone is on a vegan diet and are in good health (like you feel that you are), that’s great, I wish them well. But I personally would not go vegan again if someone offered me a million dollars to do so. It’s one of several dietary approaches I’ve tried and would never go back to.

    If a diet doesn’t work, there is no reason for anyone, ever, to stay on it. If a diet is making you sick – stop following that diet. Try another one. We don’t owe it to any diet to try to “make it work”, or to try endless variations on it because it seems to be working for other people. Whether it’s due to genetics or other reasons, some diets just do not work for some people.

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