Discovering and Defining mTOR
While mTOR is a naturally occurring protein present in the body, rapamycin was discovered first. While it is probably best known as the name of the increasingly popular longevity drug, rapamycin is a substance created by a bacteria. In the 1970s, researchers isolated rapamycin from a soil sample collected on Easter Island about a decade earlier during a Canadian expedition. Easter Island’s indigenous name is Rapa Nui, the root of the word rapamycin.
Rapamycin was initially found to have antifungal properties. Eventually, researchers discovered that it also has immunosuppressive and anti-proliferative properties in the cells of mammals. This discovery ultimately led to investigating rapamycin’s potential use in cancer treatment. In 1999, the U.S. Food and Drug Administration approved rapamycin as a prescription immunosuppressant drug.
A Tiny Worker in Our Cells
The mTOR protein helps control how cells grow and thrive based on what they need and what is available. It reads the environment and gives the orders to grow, divide, and use energy effectively. The mTOR pathway, the larger network containing mTOR and other proteins, plays a crucial role in regulating lifespan due to its ability to sense and respond to nutrient levels.Dr. Joseph Purita, who is board-certified in orthopedic surgery, pain management, and stem cell therapy and is a former president of the American Academy and Board of Regenerative Medicine, told The Epoch Times in an email that “mTOR functions as a master controller within our cells, operating much like a central command center that receives and processes signals from inside and outside the cellular environment.”
According to him, mTOR “makes strategic decisions about whether cells should grow and proliferate or conserve resources.”
How mTOR Forms Complexes
The mTOR protein is found in different cells throughout the body, but it does not live on its own. It links up with other proteins and forms two distinct multi-protein groups: The mammalian target of rapamycin complex 1 (mTORC1) and the mammalian target of rapamycin complex 2 (mTORC2). The two complexes contain different proteins, but they all play a role in stabilizing mTOR, helping it bind to target receptors.Michael T. Nelson, researcher, exercise physiologist, and specialist in metabolic flexibility, told The Epoch Times in an email that mTORC1 plays a role in cell growth and proliferation and metabolism regulation. It senses the presence of amino acids, glucose, and growth factors and adjusts cellular metabolism and development accordingly.
A Balancing Act
The mTOR protein plays a nuanced role in the body, and it is not as simple as stating that more or less of its activity is better. Modulating mTOR is about finding balance, not turning it off.“We probably don’t want mTOR running amok all the time, but we don’t really want to shut it down entirely,” Nelson said.
“Modulating mTOR activity is like adjusting the thermostat in your body’s cellular processes,” Purita said.
He said that hyperactive mTOR signaling is strongly associated with various forms of cancer. It is also linked to Parkinson’s and Alzheimer’s disease, as well as disruptions in brain growth and development. Increased mTORC1 activity can also contribute to metabolic dysfunction and heart failure and may accelerate age-related decline and increased inflammation in the body.
Conversely, he noted that insufficient mTOR signaling can lead to a cascade of adverse effects. Cells can experience decreased protein synthesis, disrupted cell cycle progression, and altered metabolic functions.
Factors That Influence mTOR Activity
Several lifestyle factors contribute to fluctuations in mTOR activity:Nutrition
Protein. Amino acids, the building blocks of protein, are known to promote mTORC1 activation. Leucine, a key amino acid found especially in animal proteins, directly activates mTORC1. Consuming protein, notably leucine-rich sources, stimulates mTORC1 activity. Purita said excessive animal protein, including red meat, chicken, tuna, beans, cheese, milk, and eggs, can lead to mTOR overactivation.However, this response to carbohydrates does not seem to have a blanket effect on all.
“The impact of carbohydrates on mTOR depends on an individual’s insulin sensitivity,” Nelson said. “People with obesity, higher body fat, or Type 2 diabetes—who have impaired insulin sensitivity—may experience greater metabolic disruptions.”
Obesity
Nelson said obesity can cause more circulating free fatty acids and that this can possibly stimulate mTORC1 via lipid signaling pathways, although not much is known about this relationship.Exercise
Resistance training, such as weightlifting, strongly activates mTOR in skeletal muscle, leading to muscle growth and strength gains. While endurance exercises can also influence mTOR, their effects are generally less pronounced than those of resistance training.“This doesn’t mean mTOR stays perpetually activated, but it does turn on when needed to support muscle growth and repair,” Nelson said.
Sleep Deprivation
A lack of sleep is known to decrease glucose tolerance and insulin sensitivity. Consequently, an insufficient night’s sleep might indirectly affect mTOR signaling by hindering insulin’s ability to activate the pathway.Chronic Stress
Though more research is needed, there is a link between stress and mTOR. Prolonged stress can lead to elevated cortisol levels, affecting mTOR activity by causing the protein levels to either rise or fall.Alcohol Consumption
Further research is needed to fully understand the diverse effects of alcohol on mTOR, but a study published in Biomolecules in 2022 found that acute and chronic alcohol use can alter mTORC1 signaling.Drinking alcohol might lessen the positive effect of exercise on the mTORC1 pathway.
When it comes to these factors affecting mTOR activity, particularly diet and exercise, once again, it comes down to finding balance.
Nelson shared his take on the bottom line with balancing mTOR: “Higher protein intakes, regular exercise, and balanced nutrition promote better health, longevity, and physical performance. While theoretical concerns about mTOR exist, the benefits of maintaining muscle mass and metabolic health far outweigh the risks.”
What About Taking Rapamycin?
The association of excessive mTOR activity with cancer and other diseases has fueled a boom in the mTOR inhibitors market, which is projected to reach several billion dollars within the next few years. Rapamycin seems to be leading the charge as the key player in suppressing mTOR activity and boosting longevity.Purita said that low-dose rapamycin is undergoing research for its potential anti-aging effects.
“Rapamycin’s effects appear robust across different mouse strains and dosing regimens, with consequential benefits observed in female mice,” he said. “However, translating these findings to humans requires careful consideration.”
Taking the drug can come with serious side effects, including an increased risk of infections, metabolic disturbances, and potential diabetes-like symptoms, Purita said. He added that long-term effects and optimal dosing strategies remain unclear.
“Long-term use of mTOR inhibitors may lead to unwanted effects on muscle growth, wound healing, and immune function,” he said. “It’s crucial to note that mTOR signaling plays complex roles in the body, and both excessive activation and inhibition can have negative consequences.”
Considering an Evolutionary Mismatch
Given what we know about mTOR activity and the importance of balance, we should consider how our present-day lifestyle has thrown its delicate harmony askew. It is easy to point fingers at protein, carbohydrates, stress, exercise, and other factors that may lend a hand in increasing mTOR activity.However, J Gulinello, a clinical nutritionist, told The Epoch Times via email that we should not overlook how much our food environment has changed from an evolutionary perspective.
Gulinello said that since amino acids are known to activate mTOR activity, the rationale for eating a low-protein diet for longevity may seem solid.
“If a disease like cancer is out-of-control cell proliferation, let’s suppress the permission slip for cancer to proliferate,” he said.
But he also said that a point seldom articulated is that insulin also stimulates mTOR, and for a longer period of time.
“When you combine that with today’s food environment where carbohydrates, specifically the refined versions, make up the base of the government food pyramid, you have consistently and chronically stimulated mTOR, which is likely not a good thing,” he said. “All the protein restriction in the world won’t solve this problem.”
Alas, it is an evolutionary mismatch.
In previous eras, periods of feasting were offset by periods of famine. This cycle was the norm, and mTOR activity is designed to function in such a cycle. A feast would flip the on-switch for the mTOR pathway, but the subsequent period of famine prevented a chronically activated switch.
The current Standard American Diet, however, consists of a surplus of nutrients with little downtime between feasts. Gulinello said this is a recipe for disaster that could lead to accelerated aging and out-of-control cell proliferation.
“We need mTOR for survival,” he told The Epoch Times. “What we don’t need or want is mTOR locked in the ‘on’ position.”
Instead of blaming a necessary internal mechanism and healthy habits such as exercise and diet, it is likely more accurate to blame our modern lifestyle and food choices, Gulinello said.
“That’s like blaming firefighters for the fires they continually respond to,” he said.
He said mTOR is not something to be feared but is something to be concerned with in the pro-inflammatory food environment we find ourselves in today.
Copy
