Peter Attia· MD
there's tremendous feedbacks Matt right that fight all of that right the system always is trying to get to homeostasis and so so David talk a little bit about um discoveries that were made in your lab about what the amino acids were doing to mtor because those actually are things that were learned much later than the initial discoveries you made around the interaction between rapid and mtor so so what do we know in particular about Branch chain amino acids uh or Lucine in particular sure so so this also has a little bit interesting backstory so when I first identified mtor in salul Snider's lab I talked to my dad who is a cell biologist and uh and he said David you have to localize mtor within the cell and I kind of to be honest with you I kind of dismissed that in maybe a little bit an arrogant way because I was like look I'm a mole biologist biochemist cell biology is kind of an old thing but we did actually make an antibody to mtor you know at the time we used to make them ourselves and rabbits we had some we purified and I added it to cells and it gave this very interesting punctate pattern inside the cell and I remember walking around the cell biology department at John's Hopkins Medical School asking people what is this right and I didn't get any definitive answer then the rabbit died the antibody was lost and literally for about that would have been in 93 or something literally until probably 10 15 years later we did not revisit this question and it was Tim Peterson in my lab who did and when he did do this and he did it in a definitive way the answer was lomes as I as I mentioned sorry just to make sure just to make sure we understand David you're saying when you did the original experiments with the antibodies and they lit up and you're walking around showing them to people saying what would light up in this pattern it wasn't clear what the answer was in other words it wasn't clear where mtor was yeah I think you know people didn't they saw dots inside the cell now it was clear that there was the little vesicles and I and I think I probably you know if I had sat down this was like literally walking around the hallway right so maybe if I had sat down with more experts and and and really showed them more experiments that we we would have gotten a more definitive answer but that didn't work and then you know you go on and again literally the rabbit died the antibody disappeared and and there was I would say no good antibody to do this experiment for the next 15 years and this guy Tim got one and he showed that again we saw the same punct tape pattern that I had seen as a student you know 15 years earlier um but he then went on to figure out what it was and they were these things called lomes again these sort of recycling centers they're they're these are compartments in the cell that have a membrane things get in them and there's about 60 enzymes in that compartment that can basically annihilate anything break it down into single components like for for example proteins amino acids come out Polymers of sugars individual sugars come out and and that was fine but the critical experiment and the one that really changed everything for us is then Tim did a simple experiment he said well let me remove amino acids and look where mtor is and it turned out it wasn't on lomes anymore it went off the lome then he added amino acids and he had even little movies within minutes it went back to the lomes and so what that told us is that nutrients communicated to mtor and one of the things they did was move mtor to the surface of the lome and then we went on and we found the docking station so it turns out you can think of mtor as like this big ship and there's sort of this docking like a pier and when it gets there it sits on top of these proteins that hold it there and it turns out that those proteins are the ones that nutrients talk to and there's an entire set of proteins about I think I count to there's about 20 proteins involved in making that communication to drive mtor to the surface of the lome and and we could go into the details of this but it's it's probably a little bit uh too much but there's multiple large protein complexes that do that communication and and what I think that indicates and I've said this in talks you know it could have been simple right there could have been one protein binds an amino acid talks to EMP but it's not there's a lot of sort of protein real estate used to do this which tells you the cell cares about this so the question becomes which amino acids and and I have to say that that really that that was broken open not by us but by Joe avick he had a paper in JB JBC where he looked at amino acid regulation of mtor this was this is before the lomes he was looking at the activity of using S6 kyes and he basically found a couple amino acids that mattered he found Lucine you know a very common essential Branch chain amino acid an important component of of whey protein for example that people take Arginine a very basic amino acid technically not essential