Introduction

If you've ever stumbled across the term mTOR and found yourself puzzled, you're not alone. mTOR, or the mechanistic target of rapamycin, is a complex and intriguing biological system that plays a crucial role in our health. In this blog article, we'll break down what mTOR is, how it works, and why it's so important for our bodies.

What is mTOR?

mTOR is a protein kinase, which means it's an enzyme that adds phosphate groups to other proteins, thereby regulating their activity. It's a central component of a larger signalling network known as the mTOR pathway, which is responsible for controlling several essential cellular processes. This pathway is present in all eukaryotic organisms, including humans, animals, and even some fungi.

The Role of mTOR in the Body

The mTOR pathway acts as a cellular communication system, responding to various signals such as nutrient availability, energy levels, and stress. It plays a critical role in managing the balance between cellular growth and breakdown, and helps regulate essential processes like:

• Protein synthesis: mTOR promotes the formation of new proteins, which are vital for cell growth and repair.
• Autophagy: This is the process by which cells recycle their damaged or unnecessary components. mTOR can suppress autophagy when nutrients are plentiful to prioritise growth, and activate it during times of stress or scarcity.
• Cell growth and division: mTOR helps control the size and number of cells by regulating the cell cycle.
• Metabolism: mTOR influences how cells use and store energy, helping to maintain metabolic balance.
• Aging: Research suggests that mTOR may play a role in the aging process, with its inhibition leading to increased lifespan in certain organisms.

mTOR and Health

Given its wide-ranging functions, it's no surprise that mTOR has been implicated in various health conditions. Dysregulation of the mTOR pathway has been linked to diseases such as cancer, obesity, type 2 diabetes, and neurodegenerative disorders like Alzheimer's and Parkinson's.

Furthermore, mTOR has become a target for therapeutic interventions. For example, rapamycin, a compound that inhibits mTOR, is currently used as an immunosuppressant for organ transplant patients and is being explored for its potential anti-aging and anti-cancer properties.

Improving mTOR functions:

Improving mTOR function involves maintaining a healthy balance in its activity, as both over-activation and under-activation can have negative consequences. Here are some strategies to optimise mTOR function and promote overall health:

• Exercise: Physical activity, especially resistance training, can stimulate mTOR activity and promote muscle growth, repair, and overall health. Exercise also has numerous other health benefits, making it an essential part of a balanced lifestyle.
• Balanced diet: Consuming a diet rich in nutrients, particularly amino acids like leucine (found in foods like meat, fish, dairy, and legumes), can help activate mTOR and support protein synthesis. At the same time, avoid excessive calorie intake and choose nutrient-dense foods to prevent over-activation of mTOR, which may contribute to metabolic disorders.
• Intermittent fasting: Periods of fasting can help regulate mTOR activity by promoting autophagy during the fasting phase and supporting cellular growth during the feeding phase. This approach may also help improve insulin sensitivity and overall metabolic health.
• Manage stress: Chronic stress can have detrimental effects on mTOR function and overall health. Develop healthy stress management strategies such as mindfulness, meditation, and engaging in hobbies that bring relaxation and joy.
• Sleep: Prioritise getting enough quality sleep, as it can influence mTOR activity and is vital for overall health and well-being. Aim for 7-9 hours of sleep per night and establish a regular sleep schedule.
• Avoid smoking and excessive alcohol consumption: Both smoking and excessive alcohol intake can negatively impact mTOR function and overall health. Reducing or eliminating these habits can help maintain a healthy mTOR balance.
• Nutritional supplements: Some supplements, such as omega-3 fatty acids, curcumin, and resveratrol, have been suggested to modulate mTOR activity, though more research is needed to determine their efficacy. Always consult with a healthcare professional before starting any supplement regimen.

Things to avoid:

There are several common habits and lifestyle factors that may negatively impact mTOR function, leading to imbalances in cellular growth, repair, and metabolism. Here are some behaviours to be mindful of:

• Overeating and excessive calorie intake: Consuming excessive calories, particularly from nutrient-poor foods, can lead to over-activation of mTOR, which may contribute to obesity, insulin resistance, and metabolic disorders.
• Sedentary lifestyle: A lack of physical activity can negatively affect mTOR function and overall health. Regular exercise, especially resistance training, is essential for promoting muscle growth, repair, and maintaining a healthy mTOR balance.
• Inadequate protein intake: Not consuming enough protein or essential amino acids, particularly leucine, can hinder mTOR activation and impair muscle growth, repair, and overall health.
• Chronic stress: Persistent stress can negatively impact mTOR function, weaken the immune system, and lead to inflammation. Developing healthy stress management techniques is crucial for maintaining a healthy mTOR balance and overall well-being.
• Poor sleep habits: Insufficient or poor-quality sleep can disrupt mTOR activity and negatively affect overall health. Prioritise getting enough restorative sleep and establish a consistent sleep schedule.
• Smoking and excessive alcohol consumption: Both smoking and excessive alcohol intake can impair mTOR function and contribute to health problems. Reducing or eliminating these habits can help maintain a healthy mTOR balance.
• Overuse of certain medications: Some medications, such as corticosteroids, can suppress mTOR activity and have adverse effects on muscle growth and repair when used in the long term. Always consult with a healthcare professional about the potential risks and benefits of any medication.

Why are Dave Aspery and Mark Hyman obsessed with mTOR? 

Dave Asprey and Dr. Mark Hyman, both well-known figures in the health and wellness industry, are particularly interested in mTOR due to its crucial role in various aspects of human health. Their interest in mTOR is primarily focused on how to optimise its function through lifestyle and dietary interventions to promote health, longevity, and overall well-being.

Some reasons for their fascination with mTOR include:

• Cellular growth and repair: mTOR is a central regulator of cellular growth, repair, and protein synthesis. By understanding how to optimise mTOR function, it may be possible to enhance muscle growth, improve recovery from injuries, and support overall health.
• Ageing and longevity: Research has suggested that mTOR may play a role in the ageing process, with its inhibition leading to increased lifespan in certain organisms. Asprey and Hyman are interested in exploring the potential of mTOR modulation as a strategy for promoting healthy ageing and longevity.
• Metabolic health: mTOR is involved in the regulation of metabolism, including energy production and nutrient sensing. Maintaining a healthy balance of mTOR activity may help prevent metabolic disorders such as obesity, type 2 diabetes, and insulin resistance.
• Disease prevention: Dysregulation of the mTOR pathway has been linked to various health conditions, including cancer, neurodegenerative diseases, and autoimmune disorders. Understanding the role of mTOR in these diseases may lead to new therapeutic interventions and prevention strategies.
• Dietary and lifestyle interventions: Asprey and Hyman are proponents of using diet and lifestyle changes to optimise health and well-being. They believe that by focusing on mTOR, individuals can make informed choices about their diet, exercise, and other habits to support optimal mTOR function and overall health.

Their obsession with mTOR is driven by the desire to help people achieve better health and longevity through evidence-based dietary and lifestyle practices. By understanding the intricacies of mTOR and its impact on human health, they aim to empower individuals to take control of their well-being and make informed choices about their habits and routines.

What about female hormones and mTOR?

Some female hormones, particularly oestrogen, can interact with the mTOR pathway and influence its activity. However, it's important to note that these interactions are complex and not necessarily negative. The impact of female hormones on mTOR depends on various factors, including hormone levels, individual physiology, and the overall health context.

Oestrogen, the primary female sex hormone, can modulate mTOR signalling in specific cell types and under certain conditions. Oestrogen has been shown to activate the mTOR pathway in some tissues, such as breast and endometrial tissue. This activation has been associated with an increased risk of certain hormone-sensitive cancers, like breast and endometrial cancer. In this context, oestrogen's effect on mTOR could be considered negative.

However, oestrogen has also been shown to have protective effects in other tissues, such as the brain and the cardiovascular system. In these cases, oestrogen's influence on mTOR might be considered beneficial, as it may help protect against neurodegenerative diseases and cardiovascular disorders.

Additionally, the hormone progesterone, which is involved in the menstrual cycle and pregnancy, can also interact with the mTOR pathway. Progesterone has been shown to inhibit mTOR signalling in certain tissues, such as endometrial tissue, which may counterbalance oestrogen's effects.

In conclusion, the impact of female hormones on mTOR is complex and depends on various factors. It's essential to maintain a healthy balance of hormones and mTOR activity to support overall health and well-being. If you have concerns about your hormone levels and how they may affect mTOR or your health, it's crucial to consult with a healthcare professional for personalised advice.

mTor and Cancer:

The link between the mTOR pathway and cancer stems from the role mTOR plays in regulating cell growth, division, and survival. When functioning properly, mTOR helps maintain a balance between cellular growth and breakdown, promoting overall cellular health. However, when the mTOR pathway becomes dysregulated, it can contribute to the development and progression of cancer.

Here are some ways in which the mTOR pathway is connected to cancer:

• Uncontrolled cell growth: Over activation of the mTOR pathway can lead to excessive cellular growth and proliferation, which can contribute to tumor development. Mutations in genes that regulate mTOR signalling or other components of the pathway can result in uncontrolled cell growth and cancer formation.
• Angiogenesis: The mTOR pathway plays a role in angiogenesis, the process of new blood vessel formation. Tumors require an adequate blood supply to grow and spread, and mTOR's role in promoting angiogenesis can contribute to tumor growth and metastasis.
• Resistance to cell death: Dysregulated mTOR signalling can make cancer cells more resistant to programmed cell death (apoptosis), allowing them to survive and continue to grow despite unfavourable conditions or damage.
• Metabolic changes: Altered mTOR signalling can lead to metabolic changes in cancer cells, enabling them to thrive in low-oxygen and nutrient-poor environments. These changes can promote tumor growth and survival.
• Interaction with oncogenes and tumor suppressors: The mTOR pathway can interact with various oncogenes (genes that can promote cancer development when mutated) and tumor suppressor genes (genes that protect against cancer). Dysregulation of the mTOR pathway can impact the function of these genes, contributing to cancer development and progression.

Given the links between the mTOR pathway and cancer, researchers are actively investigating mTOR inhibitors as potential cancer treatments. Some mTOR inhibitors, like rapamycin and its analogs (also known as rapalogs), have been approved for specific cancer types or are being tested in clinical trials. However, not all cancers respond to these inhibitors, and research is ongoing to develop more effective strategies for targeting mTOR in cancer treatment.

What stimulates mTOR?

Several factors can stimulate the mTOR pathway to become overactive, potentially leading to imbalances in cellular processes and increasing the risk of health problems like cancer, metabolic disorders, and accelerated ageing. Some factors that can contribute to mTOR over activation include:

• Excessive calorie intake: Consuming excessive calories, particularly from nutrient-poor foods, can lead to over activation of mTOR. This can contribute to obesity, insulin resistance, and other metabolic disorders.
• High levels of insulin and growth factors: High circulating levels of insulin, insulin-like growth factors (IGF-1), and other growth factors can stimulate mTOR activity. These factors can be elevated due to a diet high in refined carbohydrates, sugars, and unhealthy fats, as well as in obesity and type 2 diabetes.
• High protein and amino acid intake: Consuming excessive amounts of protein and specific amino acids, such as leucine, can activate the mTOR pathway. While some activation is necessary for muscle growth and repair, overstimulation can contribute to imbalances in cellular processes.
• Genetic mutations: Certain genetic mutations can lead to over activation of the mTOR pathway or dysregulation of the pathway's components, potentially increasing the risk of health problems like cancer.
• Inflammation: Chronic inflammation can lead to mTOR over activation and contribute to the development of various health conditions, including metabolic disorders and cancer.
• Oxidative stress: Increased levels of reactive oxygen species (ROS) can stimulate mTOR activity, leading to imbalances in cellular processes and an increased risk of health problems.
• Hormonal imbalances: Some hormones, such as oestrogen, can modulate mTOR signalling in specific cell types and under certain conditions, potentially leading to over activation of the pathway.

To maintain a healthy balance of mTOR activity and support overall health, it's important to adopt a well-rounded, healthy lifestyle that includes regular exercise, a balanced diet, stress management, and adequate sleep. If you have concerns about mTOR over activation and its potential impact on your health, consult with a healthcare professional for personalised advice.

mTOR and time-restricted feeding:

Time-restricted feeding (TRF) is a type of intermittent fasting that involves limiting the daily eating window to a specific number of hours, typically ranging from 8 to 12 hours. The link between mTOR and time-restricted feeding lies in the way TRF can modulate mTOR activity and influence various cellular processes, such as autophagy, protein synthesis, and metabolism.

During the fasting phase of TRF, mTOR activity is generally suppressed due to the reduced availability of nutrients, particularly amino acids like leucine. This suppression of mTOR activity leads to several beneficial effects:

• Autophagy: With mTOR activity suppressed, autophagy—a process in which cells recycle damaged or unnecessary components—is promoted. Autophagy helps maintain cellular health and prevent the accumulation of damaged cellular components, which can contribute to aging and various diseases.
• Insulin sensitivity: TRF can improve insulin sensitivity, reducing the risk of insulin resistance and type 2 diabetes. Lower insulin levels during fasting can also contribute to decreased mTOR activation, promoting autophagy and other beneficial cellular processes.
• Metabolic adaptations: TRF can lead to metabolic adaptations that promote fat utilisation for energy during the fasting phase, potentially supporting weight management and overall metabolic health.

• Protein synthesis: mTOR activation during the feeding phase promotes protein synthesis, which is crucial for muscle growth, repair, and overall cellular health.
• Cell growth and division: mTOR helps regulate the size and number of cells by controlling the cell cycle during the feeding phase.

By modulating mTOR activity through time-restricted feeding, it's possible to strike a balance between promoting cellular repair and growth, which can contribute to overall health and longevity. However, individual responses to TRF may vary, and it's essential to consult with a healthcare professional before making significant changes to your eating patterns.

Should we be stimulating or inhibiting mTOR?

The goal for optimal health is to maintain a balance in mTOR pathway activity, rather than strictly stimulating or suppressing it. Both over activation and under activation of the mTOR pathway can have negative consequences. Striking the right balance allows for the promotion of cellular growth, repair, and protein synthesis while simultaneously supporting autophagy, metabolic health, and overall cellular maintenance.

To maintain a balanced mTOR function and support overall health, consider incorporating the following lifestyle strategies:

• Exercise: Engage in regular physical activity, especially resistance training, which stimulates mTOR activity and supports muscle growth and repair.
• Balanced diet: Consume a diet rich in nutrients, with an appropriate intake of protein and essential amino acids to activate mTOR for cellular growth and repair. Avoid excessive calorie intake and focus on nutrient-dense foods.
• Intermittent fasting or time-restricted feeding: Implementing periods of fasting can help regulate mTOR activity, promoting autophagy during fasting and cellular growth during feeding.
• Manage stress: Develop healthy stress management techniques, as chronic stress can negatively impact mTOR function and overall health.
• Prioritise sleep: Get enough quality sleep, as it can influence mTOR activity and is vital for overall health and well-being.
• Avoid smoking and excessive alcohol consumption: Both smoking and excessive alcohol intake can negatively impact mTOR function and overall health.

By adopting these practices, you can help maintain a balanced mTOR function that supports overall health and well-being.

Conclusion:

In conclusion, understanding the mTOR pathway and its role in regulating cell growth, metabolism, and ageing is crucial for optimising health. Striking a balance between mTOR activation and suppression can be achieved through a combination of regular exercise, a nutrient-dense diet, time-restricted feeding, and stress management, while also prioritising sleep. Hormones, particularly in women, can interact with mTOR, underscoring the importance of maintaining hormonal balance. The link between mTOR and cancer highlights the need to regulate this pathway, and some supplements may help support healthy mTOR function. By adopting a well-rounded, healthy lifestyle and consulting with a healthcare professional, individuals can work towards maintaining balanced mTOR activity, promoting overall health and well-being.

References:

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Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013). mTOR is a key modulator of ageing and age-related disease. Nature, 493(7432), 338-345. https://doi.org/10.1038/nature11861

Egan, B., & Zierath, J. R. (2013). Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell metabolism, 17(2), 162-184. https://doi.org/10.1016/j.cmet.2012.12.012

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Saxton, R. A., & Sabatini, D. M. (2017). mTOR signaling in growth, metabolism, and disease. Cell, 169(2), 361-371. https://doi.org/10.1016/j.cell.2017.03.035