The discussions around mTOR have been on the rise lately. I believe this is due to the numerous documentaries on streaming services like “Game Changers” and “For the Health of It”. It has suffered some bad press, so I thought I should do a post on it. First, some historical background. mTOR is the Mammalian Target of Rapamycin in longhand. Since most life forms have it, the name has been corrected to Mechanistic Target of Rapamycin to reflect this new information more accurately. Rapamycin is an antifungal and immunosuppressant named after Easter Island, where it was first discovered. The original name of Easter Island was Rapa Nui; hence the RAPA-mycin name. in 1994 Schreiber, Sabatini, and others determined that the “target” of rapamycin is a complex they called FRAP and RAFT1, but the names never took, and we are stuck with mTOR. (1,2)

I have to give most of the credit to David Sabatini for the information contained in this post. He is the go-to person on all things mTOR related. If you want a deep dive into the subject, I recommend his series of talks found on YouTube. In a nutshell, mTOR is a structure that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress. (3) mTOR is crucial for protein synthesis and growth, both of which are needed for life, which is a good thing. With the downregulation of mTOR, we get a lowering of metabolism, and specifically, more autophagy and apoptosis. (4) Autophagy is the cell’s housekeeping mechanism, which is a good thing. It repairs damaged proteins, clears damaged organelles, such as mitochondria, endoplasmic reticulum, and peroxisomes, as well as eliminates intracellular pathogens. It is increased in times of starvation and fasting. (5) Apoptosis is programmed cell death. Most cells can only divide so many times before they become dysfunctional; this is also a good thing when balanced with new cellular division. (6)

Most people are not very interested in complex subjects like mTOR, autophagy, and apoptosis, so why the recent interest? Part of the reason is that it has become a talking point for some individuals and groups as a means of persuasion. Since the general public knows little to nothing about mTOR, the science sounds impressive to the average person. I can tell you that reading scientific papers is very tedious. If you are curious to see just how difficult it can be, try to read and comprehend the last paper I cite in this post. Click on footnote 17 for access. Three groups that like to misrepresent mTOR are the health and longevity community, those interested in curing and treating cancer, and vegans. I will discuss each group separately.

Longevity proponents believe that by regulating and controlling the expression of specific metabolic pathways and genes, you can get drastic results in your body composition as well as expected lifespan. They believe that too much growth speeds up our biological clocks, so we should have more autophagy and less growth. Their rationale is that the more housekeeping cells practice, the healthier they will be, and the longer we will live. In summation, growth equals shortening our lifespans, and autophagy lengthens our lives.

The Anti-cancer groups correctly understand the role of mTOR in cell growth and metabolism. It is, therefore, understandable that there is an intimate association between mTOR activity and cancer. (7) Hanahan and Weinberg have demonstrated that activation of the mTOR signaling is involved in some of the significant mechanisms observed with cancerous growth. (8) In the case of cancers, overgrowth and proliferation of cells is an awful situation that must involve toning down the mTOR pathway to improve outcomes.

Vegans are correctly aware that protein and amino acids (among other nutrients) increase mTOR activity. Specifically, the amino acid leucine directly stimulates mTOR as well as indirectly stimulating mTOR through its promotion of insulin release. (9) Many vegans support the erroneous view that meat causes cancer; therefore, citing the increased mTOR activity associated with protein as the cause sounds logical.

Are these claims valid? Let’s take a closer look. I stated previously that longevity proponents favor autophagy above growth. They neglect the fact that you need the trio of mTOR-dependant protein synthesis, autophagy, and apoptosis functioning in harmony to be healthy. We can’t thrive with mTOR inhibited for very long. The body can’t rely on cellular repair and ridding of cells through apoptosis indefinitely. Continuous autophagy and apoptosis without cell growth and replacement will result in wasting. In the extreme, lab animals in numerous mTOR gene deletion studies all develop severe health problems and even death during fetal development. (10,11,12,13)  

As far as cancer is concerned, blaming mTOR for the unregulated proliferation of cells is akin to blaming the engine of a car for an automobile accident. The engine propels the vehicle, and the driver regulates the speed and direction through the components of the drivetrain. Similarly, mTOR is the engine of metabolism and growth, and our lifestyles drive its behavior through nutritional and hormonal status. The claim that runaway mTOR activity is responsible for cancer is an oversimplification. mTOR is just one component of a complex disease, and we need it to survive.  

The vegan argument has no legitimate science behind it. The EPIC-Oxford study, the Cancer and Nutrition study, and the European Prospective Investigation into Cancer and Nutrition study ( all through Oxford) totaling over 110,000 participants are just three studies out of many that support my claim. They found no difference in cancer or any other health issues in health-conscious eaters, no matter their preference to include meat, the best natural source of protein, or not in their diets. (14,15,16)

The one study that plant-based diet supporters love to cite is the paper entitled “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” by Levine, Longo et al. Let me tell you why this study is misleading. The title leads us to believe that it is better to eat a low protein diet up until age 65 and gloss over the fact that, in the end, it will shorten lives!

The researchers used only a portion of the famous NHANES study and gave no reasons for their omissions. The participants filled out food frequency questionnaires that are known to be extremely inaccurate. The summary states, “[Mice demonstrate] the detrimental effects of a low protein diet in the very old… These results suggest that low protein intake during middle age, followed by moderate protein consumption in old subjects, may optimize healthspan and longevity.” The results of their study state, “low protein appears to have a protective effect against all-cause and cancer mortality prior to age 66, at which point it becomes detrimental.” (17)

The truth is that balancing mTOR, autophagy, and apoptosis does not require vast amounts of knowledge. When we tease apart disease into parts, we lose the bigger picture. Health is the harmonious interaction of the parts. Here are a few suggestions for balancing mTOR and autophagy:

• eat a lower carb/higher fat nutrient-dense diet devoid of processed carbohydrates

• don’t eat excessive calories

•  sleep well

• exercise adequately

The most essential components listed here today are adequate sleep and nutrition. If you want to, fasting for 12-16 hours each day (intermittent fasting) or a full day once in a while does wonders to slow mTOR and stimulate autophagy. An adequate diet will maximize your raw building blocks to optimize both autophagy and growth. Regulating calories will help keep mTOR in check. Higher fat paleo-type diets spontaneously result in less calorie consumption while minimizing oxidative stress. Sleep is when our body is repairing; hence it maximizes autophagy and growth as needed. Exercise will promote growth and repair through the mTOR pathway.

Inadequate muscle mass, otherwise known as sarcopenia, is a risk factor that increases with age. Resistance training maintains or increases muscle mass through mTOR stimulation, which can result in better survival as we age. We digest and assimilate protein less adequately as we age. It is wise to increase your protein intake the older you get, as the results of the study I  just went into detail about corroborates. I think we all agree that of two elderly individuals that face a grave illness, the more frail individual is at higher risk of death.