To lose weight, get the benefits of intermittent fasting & more, you want the right balance of an protein called mTOR.
Like most things in life, your body thrives in a state of balance, called homeostasis. To maintain this homeostasis or balance, you have numerous internal systems of checks and balances to keep everything in line.
“It’s about achieving the Goldilocks zone — not too much, not too little, but just right,” says Jade Teta, ND, about the body’s regulating abilities in Next-Level Metabolism.
This is where an enzyme with the name mammalian (or mechanistic) target of rapamycin — mercifully abbreviated as mTOR — comes in. Rapamycin is a natural anti-fungal antibiotic produced by soil bacteria first discovered on Chile’s Easter Island.¹
National Geographic called rapamycin “the Easter Island drug that extends lifespan of old mice.”² In 1994, researchers found a protein that directly interacts with rapamycin, which became known as mTOR.
“In simple terms, mTOR exists in almost every cell, where it controls a host of metabolic functions,” says writer David Whiteside on ThePaleoDiet.com. “It monitors numerous environmental cues, including carbohydrate and amino-acid concentrations and several growth-factor hormones. It constantly balances all these against current needs, surpluses, and deficits.”³
Finding the Goldilocks Zone With mTOR
To understand mTOR, you need to know how its opposite — called autophagy — works. mTOR is anabolic; it builds things up, like cell growth and proliferation.⁴
Autophagy, on the other hand, is a cellular spring cleaning that’s catabolic; it breaks things down (the word literally means “self-eating”). These processes are what I mean when I reference your body’s systems of natural checks and balances.
Learn more about autophagy in this episode of Ask the Health Expert.
Once, we believed that mTOR inhibited the first step of autophagy. However, recent studies show that mTOR is involved far beyond this initial step.⁵
mTOR exists as two multi-protein complexes called mTORC1 and mTORC2. mTORC1 is the most widely studied of the two complexes and responds to anabolic (building) stimuli like insulin and amino acids.⁶ Confused? It’s okay, there’s no quiz. Essentially, this just means that any time you eat, you activate mTOR.
“When we eat carbohydrates or protein, insulin is secreted, and the increased insulin levels, or even just the amino acids from the breakdown of ingested protein, activate the mTOR pathway,” says Jason Fung, MD, in The Complete Guide to Fasting.
Activating mTOR suppresses autophagy. In other words, when mTOR is turned on, autophagy is turned off, and vice versa. Checks and balances.
“Whenever we have lots of nutrition (mainly protein) and calories, we essentially tell the body that plentiful times are here,” says Puya Yazdi, MD. “mTOR is the protein that ‘senses’ this, and signals our cells to increase their working capacity and ATP (energy) production.”⁷
On the other hand, when you restrict protein and calories, such as during intermittent fasting, the opposite happens — you shut down mTOR and activate autophagy. Other mTOR inhibitors include nutrients like curcumin and EGCG in green tea.⁸
Scientists are still learning how mTOR is connected to longevity and aging.⁹ Most research about mTOR and aging so far has been done in the context of cancer. We’re still studying how mTOR impacts healthy aging cells.
What we do know is that mTOR inhibition extends lifespan.¹⁰ Researchers have linked many diseases, including obesity and cancer, with mTOR overactivation. Likewise, mTOR overactivation may increase intestinal inflammation.¹¹
Creating the right balance of mTOR and autophagy is critical for overall health. Researchers see massive potential that this balance may help with a variety of diseases, including neurodegenerative diseases, diabetes, and cancer.¹²
That brings us back to the Goldilocks zone of neither too much nor too little.
“mTOR is one of those things that’s good to have cycled,” says Yazdi. “Sometimes we want to increase it to grow muscle and improve certain aspects of cognition, while the rest of the time we want to have low levels to increase longevity, decrease cancer risk, and reduce inflammation. You see, mTOR increases energy production, but also creates more junk products.”¹³
To age powerfully, keep disease at bay, and function at our best, we want to balance mTOR and autophagy to get the benefits of both. These four strategies can help.
Strategy #1: Stop Snacking
According to Fung in The Complete Guide to Fasting, “the constant intake of food, such as snacking throughout the day, suppresses autophagy.”
That’s because every time you eat, you trigger insulin. This hormone activates mTOR and shuts down fat burning. In other words, when you’re grazing all day, you’ll rarely or never get the benefits of autophagy.
Breaking the snacking habit can be challenging, but when you eat by the plate every four to six hours, you steady blood-sugar levels so you’re less likely to struggle with those brownies your coworker brought into the office.
Learn more about eating by the plate here.
Strategy #2: Do an Overnight Fast
A simple way to balance mTOR and autophagy so you get the benefits of both is a simple overnight fast.
“Fasting 12 to 20 hours daily ramps up autophagy,” says Teta in Next-Level Metabolism, on this “natural self-healing, recycling, and regenerating procedure.”
To create that fasting window, you’ll have a healthy, balanced dinner and close the kitchen three to four hours before bed. Break your fast the following morning with a loaded smoothie by 9 or 10 a.m. Bam, you’ve created a nice 12- to 14-hour overnight fast.
To increase its benefits, you might occasionally stretch your overnight fast to 16 or even 18 hours, thereby optimizing autophagy and providing your cells with their beneficial spring cleaning.
Learn more about how to do intermittent fasting in this blog.
Strategy #3: Resistance Training
Exercise has an interesting impact on mTOR. Research shows that mTORC1 is activated in skeletal muscle and the brain. However, exercise inhibits mTOR in other organs such as your liver. The type of exercise also affects mTOR signaling to varying degrees.¹⁴
When it comes to smartly activating mTOR, resistance exercise is top-notch. According to Alan Aragon in Flexible Dieting, “mTOR is a key signaling molecule that regulates muscle growth.”
Research shows that resistance training increases muscle size and strength by activating mTOR.¹⁵ Exercising fasted can give you the best of both worlds with mTOR and autophagy.
I talk about three reasons to exercise fasted in this blog.
Strategy #4: Eat Protein (Especially Around Your Workout)
Along with weight training, research shows that moderate to high protein intake is a great way to intelligently activate mTOR.¹⁶ As I explain in this blog, most of us don’t get enough protein, and the consequences are disastrous.
Prioritizing protein in your meals and maintaining an overnight fast is the perfect way to balance autophagy and mTOR.
My favorite way to start the day is with a cup of black coffee and some resistance training. Then, I break my overnight fast with a protein-packed loaded smoothie.
Get over 60 delicious protein-packed recipes in my Loaded Smoothie Cookbook. Claim yours for FREE here.
Final Thoughts
We’re still learning about mTOR and autophagy along with how both processes, when imbalanced, contribute to health and disease.
But you don’t need to wait for science to implement these four proven strategies and get the benefits of intermittent fasting, optimal protein intake, and resistance training. They hold the key to maintaining a healthy weight, reducing your risk of disease, and aging powerfully.
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The views in this blog by JJ Virgin should never be used as a substitute for professional medical advice. Please work with a healthcare practitioner concerning any medical problem or concern. The information here is not intended to diagnose, treat, or prevent any disease or condition. Statements contained here have not been evaluated by the Food and Drug Administration.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
References:
- Li J, Kim SG, Blenis J. Rapamycin: one drug, many effects. Cell Metab. 2014 Mar 4;19(3):373–9. doi: 10.1016/j.cmet.2014.01.001. Epub 2014 Feb 6. PMID: 24508508; PMCID: PMC3972801.
- https://www.nationalgeographic.com/science/article/rapamycin-the-easter-island-drug-that-extends-lifespan-of-old-mice
- https://thepaleodiet.com/protein-fasting-and-the-mtor-pathway
- Weichhart T. mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review. Gerontology. 2018;64(2):127–134. doi: 10.1159/000484629. Epub 2017 Dec 1. PMID: 29190625; PMCID: PMC6089343.
- Dossou AS, Basu A. The Emerging Roles of mTORC1 in Macromanaging Autophagy. Cancers (Basel). 2019 Sep 24;11(10):1422. doi: 10.3390/cancers11101422. PMID: 31554253; PMCID: PMC6826502.
- Song Z, Moore DR, Hodson N, Ward C, Dent JR, O’Leary MF, Shaw AM, Hamilton DL, Sarkar S, Gangloff YG, Hornberger TA, Spriet LL, Heigenhauser GJ, Philp A. Resistance exercise initiates mechanistic target of rapamycin (mTOR) translocation and protein complex co-localisation in human skeletal muscle. Sci Rep. 2017 Jul 10;7(1):5028. doi: 10.1038/s41598–017–05483-x. PMID: 28694500; PMCID: PMC5504043.
- https://selfhacked.com/blog/mtor-natural-mtor-inhibitors/
- https://selfhacked.com/blog/mtor-natural-mtor-inhibitors/
- Weichhart T. mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review. Gerontology. 2018;64(2):127–134. doi: 10.1159/000484629. Epub 2017 Dec 1. PMID: 29190625; PMCID: PMC6089343.
- Papadopoli D, Boulay K, Kazak L, Pollak M, Mallette F, Topisirovic I, Hulea L. mTOR as a central regulator of lifespan and aging. F1000Res. 2019 Jul 2;8:F1000 Faculty Rev-998. doi: 10.12688/f1000research.17196.1. PMID: 31316753; PMCID: PMC6611156.
- Yang K, Chi H. Tuning mTOR activity for immune balance. J Clin Invest. 2013 Dec;123(12):5001–4. doi: 10.1172/JCI73202. Epub 2013 Nov 25. PMID: 24270416; PMCID: PMC3859402.
- Kim YC, Guan KL. mTOR: a pharmacologic target for autophagy regulation. J Clin Invest. 2015 Jan;125(1):25–32. doi: 10.1172/JCI73939. Epub 2015 Jan 2. PMID: 25654547; PMCID: PMC4382265.
- https://selfhacked.com/blog/mtor-natural-mtor-inhibitors/
- Watson K, Baar K. mTOR and the health benefits of exercise. Semin Cell Dev Biol. 2014 Dec;36:130–9. doi: 10.1016/j.semcdb.2014.08.013. Epub 2014 Sep 16. PMID: 25218794.
- Agostini D, Natalucci V, Baldelli G, De Santi M, Donati Zeppa S, Vallorani L, Annibalini G, Lucertini F, Federici A, Izzo R, Stocchi V, Barbieri E. New Insights into the Role of Exercise in Inhibiting mTOR Signaling in Triple-Negative Breast Cancer. Oxid Med Cell Longev. 2018 Sep 30;2018:5896786. doi: 10.1155/2018/5896786. PMID: 30363988; PMCID: PMC6186337.
- Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J, Passarino G, Kennedy BK, Wei M, Cohen P, Crimmins EM, Longo VD. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014 Mar 4;19(3):407–17. doi: 10.1016/j.cmet.2014.02.006. PMID: 24606898; PMCID: PMC3988204.
