Computer science and phd in biology from cambridge university. Doctor robert is founder, chairman and ceo, he is an accomplished surgeon, biomedical scientist and aviator. Doctors is a graduate of Columbia College and Columbia University school of engineering and applied science. He also earned his md and earned his phd degrees from cornell university. Doctor cynthia help pioneer the aging. She spent many years on the you cfs faculty from my molecular biologist and phd from mit of filmmaker and author of immortality inc. Renegade science, and the quest to live forever. Chip was one of the original employees at cnn and served as bureau chief in san francisco. Ladies and gentlemen, please join me in welcoming doctor aubrey, doctor robert, doctor cynthia, and chip walter. The be joining me on stage shortly. [applause] tonight, we have the honor of specialists in the field but we only have about 15 minutes to explore the science and quest for longevity. I would like to keep us on a story line. Chip and i have discussed this previously. We are going to stop by defining your missions, then dig into the signs of aging, and explore the strategies as well as the pros and cons of expanding the life plans and the will take questions from the audience. Lets start with chip, you have written this amazing book, immortality inc. And can you describe your mission with the book . What made you want to write the book and what are you hoping to achieve . I have always have fascinated with the idea of a long life, longevity. Its always been i think all of us are fascinated in the human, the human race has been fascinated from the beginning going back, there spread plenty of myths and arts and philosophy, religion and theres also been plenty of snake oil. So, i think when i was looking at this i began to wonder, is it possible that we are actually at a place in Human History where science, not snake oil, not myths could solve one of the great mysteries that we have all wandered about. Which is, basically solving aging. And i thought, i think this is beginning to happen. I wanted to go out on my wanted to look at that question. I wanted to in a way you might think of it as a science book, but its kind of a history book. No. I tried to find who are the key people, the big thinkers, what kind of money has to be behind it and why do we even want to do this. In the end, i hope that i was able to bring together a story that tells the tale. Fascinating story. It reads like a novel. Cynthia cannon, youre the leading asian research, briefly what is your mission there and what is your definition of success . Well, i was a professor for almost 30 years before i went to calico. While i was there i became interested in aging, partly because at the time most people thought aging was entropy and you just wear out and its more disorder and decline and thats all there is to it but if you look at nature which is he is a different species have variables lifespans. Some live a very short time and others a long time. During evolution things had to change lifespan. Id either have to be genes that somehow determines the rate of aging and it makes us age much more slowly than a dog, for example. We worked on a tiny little roundworm called [inaudible] that lives a few weeks. In my lab we look for gina changes that could extend life. We were lucky to find that mutations in a single gene could double the lifespan of the animal and keep it younger longer than normal. It wasnt long before we were able to make a few changes and give them six times living longer than normal. With these mechanisms trying to understand them it really, interested in, you know, and trying to go beyond my own lab and to help find out whether you could i dont know, first of all trans like this to humans in some way or in other words use the information that we know from studying the basic biology of animals to improve our heal health. I also when i worked at calico its a funny company because they wanted to do half just basic research and the idea just been able to do creativity driven basic research in a really kind of moonshot away, studying animals like naked mole rats which dont seem to age. Most like creatures that seem to live a really long time, for example. And also to be in a position where we could actually try to take to the clinics some of the information weve gleaned from work on animals and make discoveries at calico at the clinic so it was exciting and big an opportunity for me to turn down. Success, to me, is two kinds of success actually. One is to make there have been and i hope we can talk about this but there have been fundamentally fascinating discoveries about aging and how it works and the many different ways you can slow it down. I hope we can find another. Maybe two, three more. I think there are more big discoveries have the need to made and i hope that we really can apply what we know to huma humans. I will stop in a second but for a long time we been trying to cure diseases which is a fantastic and weve done a really, not just perfect but people dont die of infections the way they use two or Heart Disease the way they used to. But people still age at the same rate so you have more people who are older who, in some cases, arent living in healthy conditions. The hope is we can find ways like these little worms that stay healthy for a long time but maintain our health for longer periods. Thats another goal. Its not just my goal but the goal for the whole field. Its a shared goal. You put is your mission at the Research Foundation and what is success for you . Well, first of all, is this working . Is that good . Good. So really its similar to what cynthia just said. I grew up not understanding that the idea of bringing aging under medical control was a controversial concept. No one ever told me that aging was not a medical problem. And so, it was actually 1993, the same year which cynthia published her seminal paper the transform the entire field that i went through a transformation of my own because a couple of years before that i had married a biologist having previously been referred to in a different discipline of Artificial Intelligence and through her i accidentally learned a little biology but gradually i began to realize that she just wasnt interested in aging. Then the biologist i would meet and i thought what is going on. [laughter] after a year or term oh i decided i had to switch fields and work on this because the other biologists were not doing it. I do not know cynthia at that time. Time went on and obviously i made a few contributions and i do want to mention another contribution that cynthia made which is extraordinarily important but often overlooked these days when the medical applicability of this field is more established. Back in the 90s this was heretical in the extreme. The idea of saying we ought to do something about aging you would be dead if he asked for grant allocation. Cynthia was one of the first people that went out and said this. So i often said standing on her shoulders and doing what i do but for me success is all about saving lives. When i say saving lives in talking about quality not quantity. I also have to remind people that longevity is just a side effect of health. Were just doing medical research [inaudible] we are all about keeping people healthy and we think that we have a fighting chance doing so well that the magnitude of that side effect of long jevity will be rather long. Could you quantify large . We cannot quantify large. I always like to point that the human body is a machine. Its a really, gated machine but it is still a machine. As such we need to look at what happens. We know that car, for example, can be maintained in as functional a state as it had the day it was built for as long as we like. There are cars that are 100 years old today there were not designed to last more than ten, 12 years. We already know how to do really, he has a preventative maintenance on them. So the goal of our work is [inaudible] to develop medicines that do exactly the same thing but to sufficiently comprehensive preventative maintenance to eliminate the damage that the body does to itself throughout our lives in normal operation. Thereby to completely transcend lets call it the warranty. That solution is built into our bodies. Okay. Robert, you said that you believe aging is a stem cell problem and you called the genomic base Health IntelligenceCompany Human longevity inc. I know its [inaudible] when will you have arrived . Well, similarity was born out of a company that was seeking to turn living cells into medicine and we use the platform that took advantage of the unique biology and the placenta, the organ that we all know is sort of a life support system for the developing fetus. Turns out that at a time when im a neurosurgeon by trade [inaudible] i was mostly interested in finding a way to prove the outcome of those patients when stem cells first hit the airwaves. I said this might be a tool for me to improve the neurological outcome but that is what got me into the field and we made advances turning those cells into tools to control inflammation, stem cells are good at doing and stimulating regeneration. The concept of Regenerative Medicine as a means to provide or improve health is not new, not novel and its been around a long time but it was during that time when our Company Became part of a growing enterprise, a cancer focused company that i first saw david that impressed me. The data basically showed that in patients, as they age, there was a very, abrupt decline in the number of stem cells in one organ system that we were looking at, bone marrow. Turns out that if you look at the bone marrow of the baby one in about 20, 30000 cells are a stem sub in the bone marrow of an 80 yearold its one in 30 million. So, what is that tell a surgeon who is not as smart as the rest of the folks on this panel . Can we add to some cells and change things . What we did was we ran a simple experiment. We collected the placental stem cells from Newborn Research animals and gave them back to the stem cells after a section on maturity on regular basis. This skunk we studied turned out to that those animals live 30, 40 years longer so that was enough to launch a big Research Program but it intrigued us enough to say that stem cells may in fact, play a role in doing two things. Preserving performance, in other words, maintaining the structure and function of our bodies as we age and allowing the immune system to perform at optimum levels throughout our life span. That is what got us there. Our success for us is showing that these products are meaningful in the treatment of agerelated diseases, immunities and cancer that i think the future will be very bright and we are in applying them to Human Performance with the preservation of Human Performance to me is a nicer way of saying longevity. Great. I like that framing. Lets dig more into the science of aging. I think cynthia you are probably the best to explain in basic terms what is why do we age what is happening to our bodies . Well, the tissues ability to withstand stress and to function in the proper way just declines. Cells lose the tissue integrity to some extent, the cells within the tissues lose their ability to carry out their functions in the normal way and they dont coordinate their behaviors with one another as well as they use to. It is interesting, if you look at the mortality rate of a species like humans. As you know, the chance that you will wake up one morning and died that day goes up with the older you are. It goes up in a very regular way. If you plot it exponentially is a Straight Line with starting at age 30 the chance of death you know it doubles every eight and half years. Exactly. Thats the human rate and it starts when you are young. A dog it doubles much more quickly, obviously. Dogs have a shorter life span that we have but it starts when they are puppies. Its interesting because it says that there is something inside a young person and we dont know where it is in the person but its whether its in all the cells were just one place that it has program that person to aid at a certain rate. And its already there when they are young, same with dogs. That is what i think is the most interesting thing is to find out whats the programming and what is it that it creates this resilience. Its different in different species. You found the simple genetic mutation that can double or make six times the length lifespan for a roundworm so can you explain in civil terms how that happens . Whats going on . Yes, i can. It turns out that in evolution it looks as though simple organisms developed the capacity to withstand stressful conditions like the removal of food or presence of a lot of radiation or hot temperature, all different stresses. What they seem to do is the first approximation of any stretches they have a system that can make them resist all these stresses all at once. It turns out the mutation have changed in a gene and its a gene change and if we change is one of gene called [inaudible], one in the whole dna, thats all, the animals, everything changed in the animals age more slowly. How did we do that with one based change . It turns out we changed a regulatory gene like a computer programming. If you have a hierarchy of control systems and we had intervened at the high level without knowing we did at the time but now we know. We came in at a high level and we essentially because the animal dash i will say think rightdoublequote that it was under stress. What happened is this animal had reprogrammed itself and all is also now is much more resistant to any damage and the way they did that is they made proteins that take care of other proteins and repair the dna in all things they do at different levels. But they were all coordinate leaf switched so it was very interesting and those animals lived twice as long. It suggests that we dont really know exactly but some of the same properties that are systems that protect animals from stress can also protect them, if you will, from the stress of aging. Its a high level, not very expiration but whats cool about this is that if you change the same genes in fruit flies or mice they all lived longer. Mice are mammals like we are so its a universal kind of programming mechanism and they are hints that its present in humans as well. We all live a pretty long time so one of my theories is that perhaps this system is already a little turned on and off by evolution or allowing us to be naturally more resistant to the stresses of wear and tear and time. Aubrey, youve identified seven aspects of aging damage or as you call it, accumulated side effects from metabolism that eventually kills us. Could you briefly describe a couple of key side effects . How do i answer this quickly . I think the best way for me to do is jump off from what cynthia said because, as you say, we focus or i have focused on not slowing aging down but actually reversing its. Repairing the damage that the body does to itself through our lives. To truly rejuvenate people. Of course, in principle this would be far more valuable than just slowing aging down. But also, the really good thing that the concept i introduced maybe 20 years ago now that is now being taken more seriously is the idea that this might be easier to do medically then flowing aging down. One thing that cynthia touched on is that in humans we may already be somewhat adapted to doing the kinds of things that mutations in other organisms can confer. In fact, it does seem that way paid for example, if you put [inaudible] if you put them under the stress of famine then they tend to live longer but the proportion by which they live longer is much smaller than what you get in [inaudible] so the whole combination tear that we certainly dont understand. To me the goal is to figure out how much we need to understand. I look at this more as a basic scientist and i dont find things out for the sake of finding them out but i find them out in order to figure out what to do and to manipulate the data in a manner that is desirable. The kind of damage we look at with things like waste product which happens to all organisms but in different ways in different cell types and in different organisms for example, the lost of cells. We need stem cells to restore the number of cells and in order him that is perpetually losing them as a driver of the aspect of parkinsons disease. There are many examples. It means that the approach we are taking this rejuvenation approach is much a divide and conquer approach where we have to repair a bunch of different times of damage simultaneously and this is complementary to the more years to re approach that dominated the field ever since cynthia made this blew this whole thing opened with the discovery of [inaudible]. Robert, you are a pioneer in the Stem Cell Research and the use of the placenta, as you said, to treat lifethreatening diseases. You called the placenta natures stem cell factory. You said youre striving to turn themselves into medicines. Can you explain, in simple terms, how Stem Cell Therapy works and what you anticipate in the next five, ten years . Well, to try to simplify the way we believe stem cells exert their therapeutic effects i think of it in terms of that are consistent with what cynthia and aubrey are talking about which is that underlining health and adaptability and the ability to deal with disease or injury you have to have a good programming system that is intact and uncorrupted. Stem cells can be thought of as a way of preserving the fold turns probable, uncorrupted genome in a form that can be used to sort of reprogrammed the body over time. With stem cells what they do and all of us is allows for continued process of renovation and renewal. All of us most of the cells in your body are less then three years old. They have been derived from a stem cell reservoir that had been called upon to renovate your organs and tissues over time. Now, aubrey you said something which i love because of the pilot i see the same thing you talk about with automobiles. You can keep an airplane in remarkably Good Condition if you always have perfect uncorrupted replacement parts. If you replace them on a regular schedule you replace them before they fail. Failure of the system and an airplane is like a disease. You can replace that beforehand and we do that with a cell and replace a bad cell for it goes bad you might never ever develop any of these diseases or symptoms. In our world what we are trying to do is provide reliable, highquality, scalable and economical replacement parts. The beauty of the placenta is these cells are onesizefitsall. You can take a placental style and put it into an unrelated recipient and not have to match that.