mTor is a pathway that as I understand it is a bit like a central controller of cell growth, metabolism, proliferation right down to survival in every thing from yeast to all mammals. As such it plays a key role in development and ageing.
Sabatini discovered that the pathway is activated during certain cellular processes such as cancer causing tumour formation and insulin resistance to name a couple. It is deactivated in full blown diseases such as cancer and T2. Clinically, developing inhibitors of mTor such as rapamycin, has received a lot of attention with an emphasis on helping deal with solid tumours, coronary disease, transplants etc.
It has also been implicated in disorders such as cancer, cardiovascular disease, obesity, and diabetes.
The current challenge from what I've read seems to be to understand the role of mTOR signaling to coordinate and integrate overall body growth in multicellular organisms.
David Sabatini's work started with identifying that mTor was the target of the rapamycin molecule. It is this molecule that has been found effective as an immunosuppressant, anti- cancer, prolonging life in model animals (mice etc). It looks like a strong possibility that in view of the life prolonging research, there maybe an FDA approved molecule including the rapamycin property.
So as Sabatini explains this complicated pathway:
1. Nutrients, oxygen, energy and growth factors interact with mTor which is directly bound by rapamycin
2. The most interesting part for Sabatini, is that the pathway has the capacity to sense EVERYTHING. Any kind of growth factor, nutrient, stress, DNA damage everything. Somehow this system recognises it and that tells us that the cell cares a lot about regulating this system.
3. In addition, mTor is involved in all the processes in the cell that either use or make energy. So in a nutshell, this is the key pathway in regulating cell physiology.
So the driver of this process is typically food (either manipulated by caloric restriction) or obesity or different types of diet to the balance between an anabolism (the work of the liver on life supporting balance from the broken down molecules) v catabolism (process of breaking down molecules and transporting to the liver).
Thinking of our conditions of course, insulin falls within the "growth factor" category.
His more recent work has included the fact that what he calls "Caloric Restriction" prolongs life in all life, from stem cells to humans as part of a lifestyle of caloric reduction.
He and is team found that as one example the stem cells in the lining of the gut respond well to reducing calories. The amount and activity of these cells decreases. His particular interest has been that this type of cell, is usually the origin of cancer causing cells and when mutations occur the cell is transformed and acquires cancer like properties. This is called tumour initiation leading to tumour growth. Thus prolonged calorie restriction reduces the incidence of tumours, prolonging life and the two major pathways play their critical part on every occasion.
Yes there are 2, mTorc1 and mTorc2.
Both pathways are surrounded by a variety of different mutations found commonly in cancer. Insulin operates with mTorc 2.
So, a pathway such as this has to sense two types of classes of molecules to make the decision to grow or Not grow via nutrient intake and hormones such as insulin and make a decision as to whether both are present (nutrient and hormone) and so drive growth. All these factors signal to the cell via a number of steps along the pathway and thus the impact of this pathway, triggered by nutrients and hormones leads to the balance of our bodily systems and ultimately survival.
That's about the most succinct way I as an amateur is able to describe its place and importance.
Certainly the presentations of Dr Sarah Halberg that I mentioned previously focus in more on its impact for us as diabetics.
I hope I've been clear enough....if not my apologies.
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