The Master Regulator of Anabolic Activities - mTOR

From muscle growth to epilepsy, mTOR plays a role in myriad cellular processes. Learn how its levels can go from being great for athletes to dangerous for your health.

Structure and downstream:
mTOR is actually the catalytic subunit of two different complexes, mTORC1 and mTORC2. Because these two complexes have different proteins associated with them, they are localized to different areas in the body. Rapamycin acts as an inhibitor of mTORC1 but only causes inconsistent inhibition of mTORC2 in certain circumstances. From a scientific standpoint, we know a lot more about mTORC1 than mTORC2 because of the lethality in knockout mice studies. However, we do know that disrupted mTORC2 function is correlated with deregulation of insulin function. Some of the major complexes in the mTOR pathway include: PI3K/Akt, AMPK, MAPK, p53, IRS-1, PTEN, GSK-3, IGF-1, S6K, and 4E-BPs.

Fitness Benefits:

mTOR is important for cell growth regulation. In the fed state it is active and allows us to put on muscle. In the fasted state, it becomes inhibited, thus conserving energy. This was evolutionarily advantageous. For protein synthesis and muscle growth, mTOR interacts with many other proteins and complexes resulting in muscular hypertrophy. Research has shown that while mTOR acts differently across tissues, it has shown promising ability to increase and maintain skeletal muscle. Additionally, exercise increases mTORC1 activity in the brain which has been shown to increase neural plasticity which is key to improved memory and learning. It is important to note that the relationship between mTOR and skeletal muscle is understood in more depth than the effects mTOR has in tissues like the brain, liver, and fat. 

Supplementation/Modulation:

While there are no actual mTOR supplements, there are many products on the market that can alter mTOR function. Some immunosuppressants used during organ transplants are targeted toward mTOR to reduce the chances of rejection of the new organ. This is because mTOR restricts catabolic activities, thus decreasing circulating glucose (from glycogen breakdown or gluconeogenesis). With lower glucose levels, the body’s T-cells have fewer sources of energy and therefore will reduce the activity of the immune system. 

On the other hand, there are ways to increase mTOR activity for muscle growth. The most obvious way is to eat. Proteins high in leucine as well as carbs and high calorie foods can initiate mTOR’s anabolic effects. Other derivatives of leucine, like hydroxymethylbutyrate (HMB), can also increase mTOR activity.

Other implications: 
As expected, cellular growth and proliferation is not something that is always in the best interest. Overactive mTOR and its effects play a role in two major medical diagnoses, cancer and diabetes. In cancer, excessive and uncontrolled cell growth as well as cell proliferation is exactly what you do not want. There are a few anti-cancer drugs that inhibit mTOR activity.