The mTOR Pathway, Simplified

 Last week, I spoke to you about deregulated nutrient sensing. We discussed how nutrients are essential for all living organisms and subsequently, their cells. The quantity of nutrients present tells our cells if it’s a good time for them to grow or not. Our cells’ ability to tell this difference is crucial for our wellbeing. But unfortunately, this ability declines with time. This decline is called “deregulated nutrient sensing”, and is one of the nine hallmarks of ageing. Nutrient sensing by our cells happens via four pathways, IGF-1, mTOR, sirtuins and AMPK. In the previous edition we focused on the Insulin-Like Growth Factor (IGF-1), and today, we will deep dive into mTOR.

Mechanistic Target of Rapamycin (mTOR)

Rapamycin is an immunosuppressant and an anti-cancer fighting agent. mTOR is a protein which regulates cell growth, cell division, cell movement, cell survival, autophagy (cleaning out damaged cells, in order to regenerate newer and healthier cells), transcription (when RNA is made from DNA) and protein synthesis. It is the master controller of protein synthesis.

When mTOR is high, it promotes growth in the body and can even stimulate the growth of cancer and tumor cells. When mTOR is low, it works on repair and maintenance for the body. Low mTOR stimulates autophagy (recycling of damaged and old proteins into new amino acids to build new tissues). This slows down the ageing process. 

mTOR regulates anabolic metabolism, which is the process of building new proteins and tissues, similar to how the IIS pathway functions. At any given point, metabolism is either building new tissues (anabolism) or breaking down old ones (catabolism). Both, IIS and mTOR play a role in anabolism. 

While activation of the mTOR pathway is great for growth and energy, it's the opposite for longevity! Tissue growth and extended lifespans are mutually exclusive. This is clearly observable in animals. Animals that grow quickly, like mice, worms and insects, have very short lifespans. And animals that grow slowly, like elephants and whales, have very long lifespans.

Thus, mTOR pathway is a hallmark of ageing and too much activity in this pathway can also contribute to a number of chronic diseases like:

• Cancer
• Obesity
• Type-2 diabetes
• Neurodegeneration 

mTOR has been linked to multiple hallmarks of aging: nutrient sensing, maintenance of proteostasis, autophagy, mitochondrial dysfunction, cellular senescence, and decline in stem cell function.

Inhibiting the mTOR pathway improves insulin sensitivity and promotes autophagy. Inhibiting mTOR in older mice has shown increased longevity.

How are mTOR levels regulated and what can you do?

As adults, our aim is to keep the mTOR level low.

Two things that majorly regulate mTOR are:

1. Glucose
2. Amino Acids

Here's how Ketogenic Diet and Intermittent Fasting can help:

A ketogenic diet helps reduce insulin and bring protein down to a moderate level. Intermittent fasting also lowers protein levels and drives autophagy, thus reducing  mTOR level. 

Start intermittent fasting twice a week, with a fasting window of 14-16 hours. Suppression of mTOR is thought to be one of the major beneficiary effects of dietary restriction, which not only prolongs life span but also delays the onset of age-related pathologies (commonly referred to as health span) in a variety of organisms. 

The food we eat and mTOR:

mTOR pathway can be regulated with certain nutrients. Epigallocatechin Gallate (EGCG), curcumin and resveratrol have been found to be effective for inhibiting the mTOR pathway. These can be found in the following:

i. EGCG

• Green Tea (a major source)

    Found in small amounts in:

• White Tea
• Oolong Tea
• Fruits: cranberries, blackberries, cherries, strawberries, kiwis, pears, peaches, apples & avocados.
• Nuts: pecans, pistachios & hazelnuts

ii. Curcumin

• Turmeric
• Mango Ginger 

iii. Resveratrol

• Peanuts
• Pistachios
• Grapes
• Red Wine
• White Wine
• Blueberries
• Canberra’s
• Cocoa
• Dark Chocolate 

Increasing your consumption of these can also help inhibit the mTOR pathway and boost longevity.

We will talk about the third pathway ‘sirtuins’ in next week’s newsletter. Subscribe and stay tuned! 

This newsletter is a part of our ongoing series The Longevity Hack. Our aim is to help you understand the science, learn to recognise the markers of ageing and to develop biohacks for each of these. Next week, we will look at the next protein group under deregulated nutrient sensing. You can read the previous editions here. 

Curious to know more about longevity, ageing and how you can cultivate a lifestyle which will help you live longer, healthier and happier?  

Feel free to drop me a message for a 1-on-1 conversation.