Your body is really complex - and some of the functions that happen can do both good and harm. That makes it really hard to know what you should do to promote your own health and contribute to a longer lifespan.
And with this said, our focus in this article turns to mTOR. It’s a type of protein that can be beneficial for your body. But, too much of a good thing can be bad! And that’s exactly the case with mTOR. So, how does mTOR fit in with longevity pathways and what does it do?
Find out more about mTOR and how it works.
What Is mTOR?
Let’s first discuss what mTOR is and talk a bit about what it does. Now, mTOR is an abbreviation that stands for “mechanistic target of rapamycin”. It is actually a type of protein that exists in your cells.
And this protein plays a role in how cells function.
It’s involved in your metabolism, as well as your immunity and even muscle growth. One thing to note here: mTOR, as a protein, really acts on a switch. When certain things come into contact with mTOR, then it activates.
The protein only performs its functions once it’s activated. There are a couple of things that can activate the protein.
Certain nutrients are able to perform this function, but when you exercise, it’s also possible that the physical activities will interact with your cells and activate mTOR.
What you should also understand is that mTOR itself does not actually perform these functions. No, instead, it “phosphorylates” other proteins that are present in your cells - and this process actually changes certain actions of these proteins.
It is through this phosphorylation that certain functions are triggered.
That’s because the proteins that mTOR phosphorylates are the ones involved in functions like removing damaged proteins from a cell, or to control how the cell grows, divides, and differentiates.
Think of mTOR like this. It’s a protein that plays a role in ensuring your body has the ability to grow and to repair itself. It’s something that could play a role in muscle growth, but also holds potential in fat loss. Plus, mTOR can also potentially help your immune system grow stronger.
But, while all of this sounds good, too much mTOR activation can actually be a bad thing. Think about cancer cells for a moment. They are also reliant on mTOR to grow and develop. Thus, in this particular scenario, mTOR is certainly not a good thing.
There are also some concerns about mTOR activity and insulin sensitivity. Plus, mTOR may have a suppressive effect on autophagy - and your body really depends on this process to ensure waste materials in cells can be recycled.
Thus, it’s important to understand both sides of mTOR to really know how you can take advantage of it for certain health benefits, but still ensure it does not harm your health at the same time.
Discovery Of mTOR
The discovery of mTOR actually started in 1975, making it still a relatively new field that scientists still need to explore further. In 1975, the isolation of rapamycin led to a direction which helped researchers discover mTOR [1].
But, it wasn’t until 1993 that cloning TOR genes led to further advancements in this research subject.
Since these discoveries, many new studies have been conducted on mTOR and similar subjects. This has helped researchers and scientists get a more comprehensive overview of mTOR, what it does, how it works, and uncover both the good and bad sides of the protein.
Even though a lot of research has been done on the subject, one thing to keep in mind is that things are still limited. There is still ongoing research looking deeper into mTOR and how it affects health.
For example, a group of scientists created a review paper [2] where they discussed the current knowledge of mTOR. They mention that right now, there is a significant restriction in what is known about mTOR and its effect on age.
But, they do note that discoveries have been made in terms of the role that mTOR plays in things like autophagy, cellular senescence, mitochondrial dysfunction, stem cell function, and proteostasis.
And problems with these processes are often associated with older age. Thus, this leads to a potential connection between these dysfunctions and mTOR’s actions in the body.
Function Of mTOR
There are different functions that mTOR has to provide when it comes to health and well-being. This protein works at a cellular level and the function helps to ensure your cells can thrive.
So, with this in mind, let’s take a closer look at the specific functions of mTOR.
Cellular Growth
Cells need to grow and develop constantly. This is important to ensure the cell can perform its functions properly. mTOR has a role to play in the growth of cells.
One of the main ways in which mTOR helps with cell growth is by inducing protein synthesis. Now, proteins play a really important role in cellular growth. And by stimulating the protein synthesis process, it helps new proteins develop in the cell.
These proteins are really important for ensuring the cell can continue growing. Plus, they also play a role in cellular division.
Metabolism
mTOR also plays a role in your metabolic functions. Remember that your metabolism is important for breaking down food and getting the nutrients out of what you eat.
It’s another area where mTOR’s functions come into play. See, the mTOR protein is involved in breaking down nutrients into forms that your body can actually use. Plus, it also plays a role in energy production - and that helps your cells function properly.
These functions actually play a really important role in ensuring your metabolism works properly.
Immune System
Your immune system is incredibly important for your overall health. If there are pathogens entering your body, then your immune system reacts - and it sends out white blood cells to fight against those.
mTOR is actually involved in the regulation of the cells your immune system uses as “soldiers”. If it’s unable to regulate these cells, then your immune system may not work as it should.
By regulating these cells, your immune system has the capability of fighting against infections more effectively. The immune system’s cells are also important for cases where you have a wound - and properly regulated immune cells will speed up the wound healing process.
Autophagy
Did you know that your body actually has a type of “cannibalism” process? Now, one thing to notice here is that there are waste materials that build up in your cells. And what happens with these waste materials?
This is where autophagy comes into the picture. Now, autophagy is a way of cells basically “eating” themselves.
It’s an important process that allows these waste materials to be recycled. And when they are recycled, they can become healthy cellular parts once again.
In terms of mTOR, this protein helps to remove damaged proteins from your cells. If there are unnecessary proteins in your cell, then the mTOR functions by removing these as well.
These functions help to ensure your immune system and metabolic processes can work properly. Plus, it also ensures your cells are able to function properly.
Roles Of mTOR In Cellular Growth And Metabolism
As you’ve seen when we discussed the functions of mTOR, the protein actually does play a role in keeping cells healthy and ensuring they are able to grow.
But, how exactly does mTOR help with this? Let’s take a deeper dive into how mTOR affects cellular growth.
Well, first of all, let’s look at how mTOR affects cell survival. When mTOR is active, it can actually activate ATK. Then, ATK can phosphorylate different downstream targets. And many of these downstream targets are actually involved in the survival of the cell.
By activating ATK, the mTOR process can help to ensure cells divide properly. If this happens, it helps to ensure there is an abundance of different cells in your body. It’s also possible for mTOR to help increase the number of cells that are able to survive for longer.
And with these two actions, your body has the right amount of cells that live long enough to perform important functions. It also reduces the need to worry about cellular senescence.
Apart from this, it’s also important to better understand how mTOR affects protein synthesis. There are numerous proteins in your cells.
In fact, mTOR itself is also a protein - but it doesn’t really do things on its own. mTOR, when activated, affects other proteins - and this creates a chain of reactions.
mTOR has the ability to activate S6K1, which is a process that’s critical for inter-cell protein synthesis. Plus, the protein also helps to inhibit 4EBP1.
What this does is it helps to increase how many ribosomes there are. And these ribosomes play a critical role in protein synthesis.
mTOR And Autophagy
There are a lot of things that play crucial parts in cell survival - but many experts will agree that autophagy remains one of the most important processes. It’s basically a way for cells to “eat” themselves.
When autophagy happens, it creates an opportunity for cells to degrade proteins that aren’t needed, organelles, and damaged molecules. During this degradation process, the “waste” that is collected in the cell will be recycled.
And through this recycling process, some of these components can become useful again. But, that’s not the only reason why autophagy is so important. Some of the organelles and damaged particles in your cells can actually be harmful.
If autophagy happens, then it can ensure these particles are removed from the cell or recycled in such a way that they no longer pose a threat.
Now, mTOR can actually have a negative role here. Sometimes, the mTOR protein, when activated, causes problems with autophagosome formation. And this particular molecule plays an essential role in the autophagy process.
This happens when mTor phosphorylates the autophagy-initiating kinase, also known as ULK1.
Now, this ULK1 kinase regulates autophagy, and if it’s not working right, there’s no autophagosome that can engulf the different organelles, proteins, and damaged particles in the cell.
What happens now is these damaged and unneeded particles remain in your cells. And they continue to build up over time. This can cause serious damage to these cells and even contribute to cellular senescence - essentially causing the cell to die prematurely.
One thing to note is that the mTOR activity doesn’t always cause problems with autophagy.
As discussed by three researchers in a review paper [3], TOR actually contributes to autophagy - but sometimes, especially with older age, alterations to TOR are what cause issues.
That’s why a lot of interest is shifting toward the use of mTOR inhibitors to improve autophagy, especially in cases of cancer.
And when it comes to cancer, mTOR activity can actually promote the growth and division of cancerous cells, further creating a need for effective methods that target this protein.
mTOR And Aging
Age is something that we can’t really do anything about, except accept our age and do our best to stay healthy.
But, it’s a very complicated process and by better understanding why we age, we can sometimes do things to slow it down.
Sure, this won’t turn back the clock - but it can at least make you age healthily and live a longer life.
Now, mTOR does play a role in aging, but again - it’s quite complex. Now, changes to mTOR activation and activity over time can happen, and this can then contribute to certain cellular processes that are known to be associated with age.
Okay, so a normal level of activity from mTOR proteins isn’t usually a bad thing. But, as you get older, the way that mTOR works can sometimes alter - and this is how mTOR can then start to contribute to aging.
For example, it’s a process that can affect your cellular senescence. That’s a term that describes the point where a cell comes to the end of its life. It can no longer divide and will end up dying in the process.
If mTOR activates certain pathways, it can contribute to cell death. Plus, there are also some cases where mTOR activity can delay or reduce autophagy in your cells. When this happens, more organelles and other waste or harmful materials accumulate in the cell.
This does not only impact the functioning of the cell, but can also raise the risk of problems like neurodegenerative diseases and, of course, cancer!
Problems in mTOR’s ability to regulate and control things like protein synthesis, as well as the breakdown of lipids and carbohydrates, can affect metabolism.
And this contributes to more weight gain as you get older. Plus, it raises the risk for insulin resistance.
In some cases, mTOR may also reduce the production of anti-inflammatory cytokines. At the same time, there’s an increase in proinflammatory cytokines. This results in low-grade inflammation that creates a risk for rheumatoid arthritis, atherosclerosis, and several other diseases.
mTOR Inhibition
So, there seems to be a link between mTOR and aging. And while there are a couple of important roles that the protein plays, it’s important to note that it’s not all good. See, sometimes, mTOR can work against you - such in the case of cancer.
Now, remember how we talked about the fact that mTOR is involved in cellular growth and division? Well, it plays the same role in cancer cells. Thus, if there are cancer cells, then mTOR can actually make the cancer worse!
And that’s where mTOR inhibition comes into play. Now, you don’t want to stop the process completely. It still has important functions to offer your body. But, sometimes, it’s a good idea to at least limit mTOR.
There are certain ways in which you can inhibit the functions of mTOR. This is an emerging research field, especially when it comes to the treatment of cancers.
Now, a popular pharmaceutical option that is being studied is called mTOR inhibitors.
Among these drugs, the most common ones are rapalogs. These drugs essentially focus on stopping the mTOR process from working correctly. And this can be useful when it comes to treating a disease like cancer.
When these drugs are able to suppress mTOR activation, it helps to reduce the rate at which cancer cells are able to grow and divide.
This action won’t actually kill the cancer, but it may give the patient a better chance of survival when additional treatments are used to kill these cells.
It’s important to note that this particular action is not just helpful in cancer. Researchers are also investigating other areas and diseases where the use of mTOR inhibitors could be useful as a therapeutic option.
For example, hyperactivity of mTOR can sometimes cause problems. This is seen in patients with Parkinson’s disease, for example. And when mTOR activity is inhibited or at least reduced, it may yield certain benefits for the patient.
Should You Attempt To Inhibit mTOR Yourself?
We’ve taken a look at both the good and the bad sides of mTOR. And now, you might be wondering whether it could be a good idea to inhibit mTOR yourself. But, the truth is, it’s generally not a good idea.
What you need to understand is the fact that mTOR does play an important role in your cellular survival, differentiation, and even division. The process is essential for cells to grow.
There are some cases where mTOR inhibition can be useful - but these are generally medical cases where it is required to stop cancer growth or to assist with problems like neurodegenerative diseases.
If you decide to implement strategies that are going to inhibit mTOR without a need for it, then you may start to experience various complications and side-effects.
Since mTOR is critical for ensuring your metabolism is regulated properly, one of the first things that may happen is weight gain. And with this weight gain comes overweight and obesity - at the point of obesity, your risk of diseases like type 2 diabetes and heart problems increases.
The role of mTOR in muscle growth should be mentioned here too. If you’re going to deliberately inhibit mTOR, then it can result in muscle wastage. You may start to feel that your muscles are getting weaker. It’s also difficult to retain muscle mass in this situation.
Another important reason why you should not try to inhibit mTOR is due to the increased risk of insulin resistance you would then face.
Remember we discussed the fact that mTOR plays a role in regulating metabolism - and this includes the process of breaking down carbs and glucose.
When you inhibit mTOR, regulation of the breakdown of carbs, proteins, and other compounds into usable forms of energy will be adversely affected. And what happens here is that too much glucose may end up circulating through your bloodstream.
This results in high blood glucose levels and can contribute to insulin resistance. When you are insulin resistant, it sets you up for type 2 diabetes.
We also need to focus on cancer here too. Okay, so in cancer, mTOR can actually be bad - it can help those cancer cells grow. But, if you inhibit mTOR, its functionality in regulating the growth of cells becomes less efficient.
This can increase your risk of cancer, so be sure to keep this in mind too.
Instead of considering whether you should inhibit mTOR yourself, rather focus on how things like a healthy diet, an exercise plan, enough sleep, and stress management strategies could help to keep mTOR activation under control.
This can help to ensure the protein functions properly without negative alterations.
Emerging Research And Discoveries
Researchers are constantly working on new ways to treat diseases - even those diseases that are often thought of as incurable. mTOR and its different pathways have been a focal point of many studies in recent years, and in the future, it will continue to be an important focus.
This is due to the many discoveries that have already been made in terms of mTOR. It’s something that has positive effects, but sometimes it can also cause problems.
In recent news, ASX firm has announced their current investigations into the use of mTOR inhibitors in order to assist with cancer treatment [4]. The drug that they are developing is called Monepantel, or just MPL for short.
Now, this particular drug is being developed for use in two specific scenarios.
First, it is suggested to be a useful drug in the treatment of cancer growth. Additionally, the drug is also proposed to be used in the treatment of certain neurodegenerative disorders.
ASX did mention motor neurone disease, also known as MND, as one of the potential diseases that could be treated with their lead drug.
Something to note is that ASX has advised that there could be more widespread effects that come to realization when this drug is used. For example, the effects of the mTOR inhibitor could potentially even have anti-aging effects in the user.
Another important advance that was made in recent years is the development of a new mTOR inhibitor drug generation. Both first and second-generation mTOR inhibitors have existed for some time.
But, in one scientific paper [5], researchers explain how both first and second-generation mTOR inhibitors were combined in order to form the newer third-generation drug.
Researchers explain that there are challenges faced by the current generation of mTOR inhibitors. In particular, resistance to the molecules used in these drugs remains an important obstacle that limits the ability to effectively target cancer cells in the human body.
The major problem here is mutations that have been found in the mTOR proteins that are active in cancer cells.
When the proteins mutate in response to the mTOR inhibitors, it makes it harder to target these pathways in the treatment of cancer.
By researching new ways to overcome this resistance, it’s possible to deliver more efficient cancer treatments.
mTOR In Neurobiology
In Neurobiology, there are a couple of things that can activate mTOR (turn the switch on).
Similar to mTOR in other parts of your body, certain nutrients and growth factors can turn it on. But, when it comes to the nervous system, stress signals are also able to have this reaction.
Now, once it’s activated, it will phosphorylate different downstream targets. To put it simply, mTOR makes changes to downstream proteins - and it is these proteins that then need to perform certain functions.
And when this happens, mTOR essentially affects gene expression, autophagy, and protein synthesis in the cells of your nervous system. But, we should take a closer look at the specific functions that mTOR performs in your brain and nervous system too.
Neurogenesis: Neurons are really important for your brain to function properly. And mTOR is actually a critical protein for the production of new neurons.
Neurons actually generate electrical signals. And these signals are known as “action potentials”. What they do is transmit information - often over long distances.
In one review paper, researchers explain that a deficiency of mTOR or abnormalities in its functionality is linked to various problems with the nervous system. For example, certain abnormalities have been associated with seizures and autism [6].
The paper also explains that mTOR is known to contribute to cellular growth, proliferation, and differentiation within the brain and the rest of the nervous system. This further explains the important role that mTOR does seem to play in neurogenesis.
Neuroprotection: There are many things in the modern day that can cause damage to neurons and even the cells that are part of your nervous system. Consistent stress, poor dietary choices, oxidative damage - these are only a few examples.
This is another area where mTOR comes into play. Now, the specific functions that mTOR performs helps to provide protection for your neurons against these damages and injuries.
Plus, it also seems like mTOR plays an important part in ensuring your neurons can be protected against damage resulting from disease or an injury. Thus, mTOR has a neuroprotective role to play in your nervous system.
Autophagy: Once again, we need to talk about autophagy. As you should be able to recall, autophagy is the process where cells essentially “recycle” waste and unnecessary proteins. It’s a way for cells to continue thriving.
And mTOR helps to regulate the process of autophagy in the nervous system and brain cells too. When mTOR does not function properly, then a large amount of damaged and unnecessary molecules can collect inside these cells.
This can affect how well these cells are able to function - and poor functionality of brain cells can cause problems. For example, it may increase the likelihood of developing neurodegenerative diseases (like Parkinson’s and Alzheimer’s disease).
Synaptic Plasticity: Synaptic plasticity refers to how well your synapses can adapt and change over time. It’s a critical element for both memory and learning. Things like learning, stress, and experience are all factors that can affect your synaptic plasticity.
Now, when it comes to talking about synaptic plasticity, there are two types that we should mention. These include short-term plasticity and long-term plasticity.
In short-term plasticity, we talk about changes to synaptic strength that lasts for a maximum of a few hours. Long-term plasticity, on the other hand, rather refers to these changes that last for a much longer period of time.
And yes, it’s another area where mTOR comes into the picture. Synaptic plasticity also involves the ability of neurons to change their connections. And when your mTOR proteins are malfunctioning or deficient, it can cause problems.
Thus, mTOR contributes to proper synaptic plasticity. And in turn, this helps to ensure you are able to learn new things and recall memories with greater ease.
Okay, we can see that there are benefits that mTOR offers in terms of neurobiology. But, another thing that we should consider is that excessive activation of mTOR in the brain and nervous systems can actually result in problems.
That brings us to another research area - researchers are also looking into methods where mTOR inhibitors could potentially offer therapeutic benefits in certain neurological and neurodegenerative diseases.
For example, when mTOR inhibitors are used in patients who experience epilepsy, the frequency of those episodes may start to decline.
This may be a breakthrough in terms of helping these individuals get through their daily lives without worrying about epilepsy.
One study [7] conducted an experiment on laboratory rats. The study subjects (rats) had Parkinson’s disease. The researchers explain that one of the major challenges in managing the motor symptoms of Parkinson’s disease is to target L-DOPA.
The researchers note that there is a hyperactivity of mTOR activity in Parkinson’s disease. This hyperactivity is caused by the hypersensitivity of D1 receptors. The researchers used Temsirolimus, an mTOR inhibitor that has received FDA approval.
The severity of Parkinson’s motor symptoms was reduced when mTOR activity was inhibited with this medication.
Frequently Asked Questions
Is mTOR good or bad?
It’s neither good nor bad. mTOR is a really complex signaling pathway and it plays vital roles in different cellular processes.
It’s important for autophagy, but als for metabolism with the cell. mTOR also plays a role in the growth of cells. Too much, however, can be harmful.
What is the role of mTOR?
mTOR is activated by certain nutrients and growth factors. And once activated, it helps with things like protein synthesis, and it controls certain elements that are involved in cellular growth and metabolism.
It’s also involved in the regulation of cell survival and proliferation.
What does mTOR do for muscle growth?
mTOR does play a role in muscle growth. The signaling pathways that mTOR targets will essentially help with the synthesis of important proteins, as well as cellular growth in muscle cells.
It’s also important for cell differentiation and the survival of your muscle cells.
What is mTOR for dummies?
Think of mTOR as a switch. When you eat, take certain supplements, and while you exercise, it switches to “on”.
And once switched on, mTOR helps your body grow, as well as play a role in ensuring your body can repair itself.
Does mTOR speed aging?
Yes and no - the fact is, right now, there’s not enough evidence to really provide a concise answer.
Sometimes, inhibitors of mTOR may help to extend the lifespan, but current studies that show this evidence are based on laboratory rats and not human subjects.
Does fasting inhibit mTOR?
Yes, if you follow a fasting lifestyle, then it does seem to inhibit mTOR. This is mostly because fasting reduces how many nutrients are available in your body - and nutrients are one of the things that activate mTOR.
Conclusion
mTOR is one of those more complex processes that happen in your body. It’s something that can be both good and bad. So, you need to thoroughly understand what the protein does and when it can be harmful.
Follow the guidance that we shared in this post to help you know how you can inhibit mTOR in such a way that it still provides beneficial effects, without experiencing side-effects linked to this protein.
References
Experimental Approaches in Delineating mTOR Signaling. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397015/
mTOR as a central regulator of lifespan and aging. Retrieved from https://pubmed.ncbi.nlm.nih.gov/31316753/
mTOR pathways in Cancer and Autophagy. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789368/
PharmAust looks to patent anti-cancer drug. Retrieved from https://www.businessnews.com.au/article/PharmAust-looks-to-patent-anti-cancer-drug
Overcoming mTOR Resistance Mutations with a New Generation mTOR Inhibitor. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902179/
Role of mTOR Complexes in Neurogenesis. Retrieved from https://pubmed.ncbi.nlm.nih.gov/29789464/
mTOR inhibition alleviates L-DOPA-induced dyskinesia in parkinsonian rats. Retrieved from https://pubmed.ncbi.nlm.nih.gov/23938307/
