Inhibit the mTOR pathway to improve longevity
When we hear the word TOR, it’s easy for our mind to take us back to the epic story of the Norse God of Thunder. And, nothing to do with it! In today’s post we are going to explore a different concept that, although it does not have the same glamour, is just as fascinating: What is the mTOR? And what relationship does it have with longevity?
A bit of history
Biologist David Sabatini, when he first landed on remote Easter Island, also known as Rapa Nui, found it “a magical place” and was captivated. There, in the bacteria of the soil on which the famous moai stand, a scientific expedition identified in 1975 a molecule unknown until then, a surprising molecule: rapamycin, which was named in honor of the island. In this discovery, it has been revealed that this molecule has a crucial role in inhibiting the growth of certain tumors.
What is mTOR?
mTOR comes from the name or “mammalian Target of Rapamycin”. It is a protein that regulates various cellular functions, including growth, division (or proliferation), metabolism, autophagy, in addition to cell survival. Activating this signaling pathway is essential to ensure the survival of the species, as it is involved in the regulation of basic processes such as cell growth.
There are two main complexes in the mTOR pathway: mTORC1 and mTORC2. While mTORC1 is best known for its role in regulating cell growth and protein synthesis, mTORC2 is involved in controlling metabolism and cell survival. Dysregulation of this pathway has been associated with various diseases, including obesity, type 2 diabetes, and cancer, as well as the aging process.
In simpler terms, every time we consume a very copious meal and, above all, rich in proteins and calories, we are sending a message to our body that times of abundance are coming. mTOR is the protein that “senses” it and mobilizes our cells to increase their work and energy production (ATP). In this way, cells divide and multiply rapidly, and thanks to this, prepares the body for greater growth and repair.
However, mTOR is not something that we should always have active. At certain times it is better to have it activated and at others inhibited. For example, at some times in our lives, activating it can be beneficial to increase muscle mass or even to improve cognitive functions. But at other stages, especially in maturity, it is advisable to keep their levels low to promote longevity, reduce the risk of cancer and reduce inflammation.
Relationship between mTOR and Aging
The mTOR pathway is a complex network of signals. This pathway acts as a sensor for nutrients, especially amino acids, and responds to energy availability, allowing cells to adjust their behavior based on environmental conditions.
One of the most promising strategies in longevity science is the inhibition of mTOR in older ages. This approach seeks to prevent the advancement of aging by reducing overgrowth and cellular senescence.
While inhibiting mTOR has potential benefits for longevity, it is crucial to maintain a balance, as mTOR also plays an important role in immune response and cellular maintenance. This includes that reducing muscle mass is also not good with aging because it increases frailty.
Diseases and mTOR
mTOR dysregulation is linked to a variety of diseases, including cancer, obesity, type 2 diabetes, and neurodegenerative disorders. Recent research suggests that inhibiting this pathway can positively influence life expectancy.
The active substances or medicines that act against mTOR are known as rapalogos. These active ingredients have very wide potential applications, especially in autoimmune diseases, neurodegenerative diseases and disorders related to abnormal cell growth.
Drugs that inhibit the mTOR pathway are mainly used as immunosuppressants to prevent transplant rejection and in cancer therapies. The main ones include: Tacrolimus (Prograf, Advagraf), Sirolimus (Rapamune), Temsirolimus (Torisel), Everolimus (Afinitor, Zortress). But these drugs are not recommended to be taken except and their use should always be indicated by a health professional.
In addition to medications, some natural compounds can also inhibit mTOR at specific concentrations. Early research suggests that practices such as protein restriction, calorie restriction, exercise, and certain supplements such as resveratrol, omega-3s , and green tea may influence mTOR activity. Other substances such as curcumin, caffeine and various flavonoids have also shown potential in this area.
Mechanisms of Action of mTOR Inhibition
- Autophagy: Autophagy is an essential process for cleaning damaged cellular components and regenerating healthy cells. Inhibition of mTOR promotes autophagy by turning off protein synthesis and allowing cells to focus on recycling their components. Not only does this help maintain cellular health, but it can also prevent age-related diseases such as Alzheimer’s and Parkinson’s.
- Reduced Oxidative Stress: mTOR activation has been associated with an increase in the production of reactive oxygen species (ROS), which can cause cell damage and contribute to aging. By inhibiting the mTOR pathway, ROS production can be reduced, thereby improving cellular health and extending shelf life.
- Improved Insulin Sensitivity: Insulin resistance is a key risk factor for the development of metabolic and cardiovascular diseases. Inhibition of mTOR improves insulin sensitivity, which can prevent type 2 diabetes and other conditions associated with age.
- Metabolism Regulation: The mTOR pathway is closely related to energy metabolism. Its inhibition can help improve metabolic function, reduce fat accumulation, and promote a healthier lipid profile, which in turn can have a positive impact on longevity.
Calorie restriction refers to reducing caloric intake without causing malnutrition. This approach has been shown to extend shelf life by reducing oxidative stress, improving insulin sensitivity, and promoting autophagy, a cellular cleansing process that removes damaged proteins and organelles. The mTOR pathway plays a key role in these processes, and its inhibition appears to trigger responses similar to those seen in calorie restriction.
Conclusion
The future of research on the mTOR pathway and its relationship to longevity is promising. As we advance our understanding of the mechanisms underlying aging, new strategies and therapies are likely to emerge that can help improve quality of life in the later stages.
The mTOR protein is a fascinating regulator of our cellular functions, a true gatekeeper that, depending on how we activate or inhibit it, can influence our health and longevity. As science advances, a world of possibilities opens up to use this knowledge for the benefit of our well-being. So, the next time you think of TOR, remember that there’s a lot more behind this term than just mythology.
Science also has its own epic story!
Bibliography
Huang S. Inhibition of PI3K/Akt/mTOR signaling by natural products.
Wu Q, Lv Q, Liu X, Ye X, Cao L, Wang M, Li J, Yang Y, Li L, Wang S. Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review. An 20:14:1083875.
