by Nils Osmar. Dec. 21, 2022. 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.
Turning on AMPK
Anything that suppresses mTOR tends to switch on AMPK. The drug rapaymycin is an example. (The word “mTOR” stands for “mammalian target of rapamycin”). (Rapamycin has been shown to have dramatic life extending effects in many lab animals. The mechanism is believed bo be the fact that it’s turning off mTOR while switching on AMPK.)
We don’t need drugs, though, to turn off mTOR and turns 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.
Both protein and carbohydrates can switch on mTOR and switch off AMPK. (Anything which triggers the release of insulin will also turn on mTOR.) Animal-based meals that are rich in the amino acid leucine are potent mTOR activators. So are plant-based meals that are rich in high-glycemic carbs.
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 to 5 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.
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 “on” for at least 126 hours. This still gives me lots of opportunities to activate mTOR.
What I’m doing
I’m currently working out with weights three days a week, and doing cardio, aerobics, Zone 2 or HIIT on three other days.
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, and hour or two after working out.
Re: my schedule, it varies. I’ve tried different approaches in the past. Sometimes I just eat within a four hour eating window, regardless of the day of the week, keeping most meals animal-based. But sometimes, if I really want to focus in on AMPK and mTOR activation, I’ll follow the regimen below.
- MONDAYS – WORKOUT DAY 1. I work out fasted, then eat a high protein animal-based breakfast. For example, I might eat several eat eggs scrambled in with sardines and oysters for breakfast, along with broccoli and tomatoes. My later meals on these three days are high in protein and animal-based too.
- TUESDAYS – FASTING DAY 1. I do a 38 hour fast (from Monday night through Wednesday morning) (Or if I get hungry or feel like I need more nutrients, I may eat a meal on Saturday afternoon.)
- WEDNESDAYS – WORKOUT DAY 2. Another high protein animal based day. See Monday.
- THURSDAYS – FASTING TILL 1 P.M. I usually get up around 7, fast till noon, then have an 8 hour eating window.
- FRIDAYS – WORKOUT DAY 3. Another high protein animal based day. See Monday.
- SATURDAYS – FASTING DAY 2. I do a 38 hour fast (from Friday night through Sunday morning. (Or if I get hungry or feel like I need more nutrients, I may eat a meal on Saturday afternoon.)
- SUNDAYS – No fasting or working out. “My day off.”
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.
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.
- In a nutshell, I’m trying to strongly activate mTOR and IGF-1 three days a week.
- On those three days, I work out fasted in the morning, then eat a high protein, animal-based breakfast, lunch and dinner.
- To make sure I’m not getting too much mTOR activation, I do two 36 hour fasts every week; do some time restricted eating on feasting days; and have some days in which I eat plant-based, lower protein meals.
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.
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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