 Hello and welcome to NewsClick. Today we have with us Dr. Satyajit Rat from National Institute of Immunology to discuss a set of issues which have sort of come out in public eye recently. Satyajit, first question. There is this recent paper in Nature which seemed to have shaken up a lot in the gerontological discourse that finally we have something which is very important. This is really regarding the aging in mice, some experiments which have been done in Mayo Clinic. Can you tell us what this is all about? It is a little inappropriate perhaps to discuss the problems of aging in a young country like India although on this forum it is probably more appropriate. But that said from the Mayo Clinic the researchers who have published this week's paper in Nature that has attracted so much attention have done something interesting. They have taken a protein which for many years people have known is expressed at relatively high levels in cells, cells mind you not animals that are elderly, senescent elderly. Now what exactly it means for cells to be elderly is a whole different can of worms altogether that we can talk about. But the fact remains that this protein therefore marks cells that are elderly by being very highly found in them, found at very high levels in them. So the researchers reasoned that if that is the case then in a mouse that is aging there will be elderly cells and there will be non-elderly cells because all cells are not exactly the same age. More correctly, there will be cells that have undergone a transition to being functionally elderly that is they are not functioning nearly as well. It is supposed to be that each cell has a replication limit so some cells have reached closer to the replication limit others have not. Is that a part of this issue? Well yes and no actually more honestly no. The difficulty is that this replication limit that has been much discussed as the Haiflich limit and so on and so forth is a phenomenon in tissue culture. You have to take cells outside the body you have to grow them and that is where this limit is relevant. It is entirely unclear whether it has anything to do with what happens in the body and all sudden done where we are interested in aging if at all is in the body. So this is therefore completely empirical here is an association of a protein that is expressed at high levels in functionally elderly cells. So they did a what is a really very clever experiment certainly at least in hindsight it is a very clever experiment. They said if that is the case then this protein marks elderly cells. So supposing in the mouse we kill off all functionally elderly cells. Is it that functionally elderly cells create the problems that we associate with aging? Inability to think clearly bent back, doddering gait, cataract of the eye, cataract, falling hair, gray hair, all sorts of things. So see I told you it was very appropriate for us. So and to do this they used a remarkably interesting technology that they have been involved in developing that is they took the same genetic element that controls the expression of this protein but they used that genetic element to control the expression not of this protein but of another protein. So now when they created a mouse that carries this gene a transgenic mouse that carries this gene in all elderly cells along with this original mark marker protein it's called p15 ink 4a but it really doesn't matter. All the cells that show high expression of the elderly protein will also show high expression of the introduced protein. So you have now added a second marker for elderly cells but the second marker has an interesting property. When the second marker protein is expressed on the cell surface so it's a you can see it sticking out of the cell. When you put in a drug and their paper identifies the drug as AP it's got a number it's not really a drug drug in the sense of being a market drug but a chemical compound. This chemical compound when it binds to this marker protein kills the cell. Now what that means is that when they treat with the drug they can kill specifically the elderly cells the functionally elderly cells. So they did a whole set of experiments with aging mice. Now they were in a hurry because they have to publish in nature and so on and so forth but apart from that they used a genetically mutated model. Genetically mutated is something of a repetition but anyway a mutant mouse model that's known to go into premature elderlyness and has all the diseases of premature elderlyness. It's called the progeroid mouse the gene that's mutated is called bub or some R1 or whatever it is. It doesn't matter really. All that we need to know is that in all physiological systems this progeroid mouse shows accelerated elderly functional defects. Now in this mouse either from day one or from the time that symptoms of elderlyness in a variety of organs the eye the kidney the heart the muscles the skin symptoms of elderlyness begin to be visible they began treating with the drug killing of cells and these findings are simple and straightforward that if you start from day one the mice remain healthy they do not develop the symptoms of elderlyness the functional defects of elderlyness anywhere near mice not treated with the drug even if you start the drug after symptoms of elderlyness and functional defects have begun you stop them in some instances you in fact even reverse them. So does it look like that this could be in that sense of major breakthrough in aging medicine of aging and so on or do you think that well you know it's interesting but we really have to see. So I'm going to say this because in the popular press there has been talk about a drug to combat aging and remember this drug only combats aging in this particular transgenic mouse it doesn't do so in the normal mouse because of the marker second marker introduced because the transgenically introduced marker protein is what the drug uses to kill functionally elderly cells. So the drug doesn't do anything to normal mice so it's clearly not a drug but you can certainly imagine that once you say that killing of functionally elderly cells allows you to reverse the symptoms of aging then the field and I'm sure this is already happening the field is going to start looking at functionally elderly cells for some specific markers that all functionally elderly cells express through which one can specifically try to get rid of them. This is sort of going to be one of the major grails as it were of gerontological research I'm quite sure will it succeed will it work I don't know my guess is that the differences between elderly and non-elderly cells are quantitative are sort of analog if you will rather than binary it's not as if non-elderly cells will have no expression of a given protein and elderly cells will have will have very high expression it's going to be a much more graded issue and therefore we're always going to have to worry about how many cells are we killing as elderly that are not really elderly and how much damage is that doing and so on and so forth. So treatment I doubt is going to be easy or soon but it is an interesting phenomenon for people to think about in an effort to live healthy lives not long lives these mice don't necessarily live longer but they live healthier lives and also in done healthy aging would be socially much more responsible perhaps than simply longevity. So it does appear that it is it is something which is interesting as possibilities but will you really have to watch before you can sort of bring it to the table. Absolutely as a matter of fact the most interesting thing about the paper is that we really don't understand why killing of elderly cells brings about such a profound change it's a little nasty to your discipline but we don't understand how or most of where this is in any case. Oh absolutely here's here's here's one more that we thought we understood and now it turns out we don't.