 Welcome back to the third annual Vail Scientific Summit. Recently, I had a chance to chat with Dr. James Kirkland of the Mayo Clinic. He was one of the keynote speakers talking about a very hot topic at the summit, aging. So check it out. So Dr. Kirkland, you were the keynote speaker at the opening night festivities. Can you tell everybody a little bit about what you work on at the Mayo Clinic? Our interest is on drugs that target fundamental aging processes that so far appear to be working that way in mice and other experimental animal models. And what we want to do is translate these drugs into clinical application and take them through clinical trials into people, not to extend lifespan, because that would be a very tall order, but mainly to target age-related chronic diseases and potentially target them as a group. It appears that fundamental aging processes are upstream of these kinds of age-related diseases. Indeed, aging is the biggest risk factor for most of the chronic diseases that account for the bulk of morbidity, mortality, and health costs in the US, as well as what we call the Jayatric syndrome. So that seems like difficulty walking, falling, muscle weakness, mild cognitive impairment, and other conditions, as well as what we call loss of resilience, which tends to occur in older people, such that older people have prolonged recovery if they've had surgery or if they've had pneumonia or a heart attack. Or they may not even be able to do things like running a marathon, as well as when they're younger, because that's an added stress. So that's a failure of resilience. So the particular fundamental aging process that my laboratory and several others at Mayo and of course around the country and around the world is interested in is a process called cellar senescence. We're interested in developing drugs that target these cells and then taking them through to people to see if we can alleviate or prevent or delay age-related disorders as a group instead of picking them off one at a time. Well, senescence has multiple meanings and connotations. It comes from the Latin word, senox for old man. But senescent cells, it's a little bit of a misnomer because you can find what we call senescent cells even in developing human embryos. So these cells can appear at any point during the lifespan in response to damage, stress, or metabolic disturbances. So senescent cells tend to accumulate with increasing age because of repeated divisions of cells and also because of accumulation of damage that occurs over the years. But they also are evident at the sites of causation that the starting sites of age-related chronic diseases. For example, you find these cells around lesions in the arteries that result in heart attacks or strokes. You find these cells in the eye in age-related blindness. You find them in the brain in certain regions in Alzheimer's disease or in Parkinson's or other neurodegenerative disorders. You find them in the joints in osteoarthritis. You find them in bone in osteoporosis. You find them in fat tissue and diabetes and the list goes on and on and on. We know that these cells produce things or at least some senescent cells produce things that damage cells around them and also at a distance. So our view has been potentially removing these cells might alleviate not only things that occur as animals or people grow older but also age-related diseases. And that appears to be the case. So how do you go about removing them? We use a number of approaches to try to test this hypothesis. We don't want to interfere with the generation of senescent cells because senescent cells act as a way of preventing a cancer from developing. Cancer cells can become senescent and part of cellular senescence involves what we call replicative arrests. These cells lose the ability to divide. They also kill the cells around them. So if you've got a developing cancer, these cells can help to kill the cancer. They are resistant to killing themselves because they have what we call pro-survival pathways that defend themselves against the noxious things that they produce. But if they start to accumulate in sufficient numbers, they begin to cause problems throughout the body. So what you don't want to do is interfere with the capacity of the body to make senescent cells. What you want to do is get rid of them once they're there because if you get rid of them, not only are you getting rid of the cells that cause dysfunction and making people feel sick and all the rest of it, you're also getting rid of pre-cancerous cells. Wow. So are there things that people can do to help themselves age well? That's a difficult question to answer. There's emerging research about a number of things that we know, common sensings, of course, like having a balanced diet and not overeating and all of these sort of things are clear. Exercise is pretty clear, at least in experimental animals that it works. The problem with lifestyle modifications or interventions is that they're hard to get people to follow. We know that if you eat a bit less, you're likely to live a bit longer and actually you're gonna have less senescent cells and less evidence of other fundamental changes that occur related to the biology of aging than people who don't exercise or who eat more. But it's very hard to convince people of these things and to get these things adopted as public health policies. For example, it took us over 40 years to convince people not to smoke. Our view is that if there are interventions that can be developed that would supplement these lifestyle sort of things which people should be doing, that might be a way of engaging a larger segment of the population and having the opportunity for people to have an increase in their health span ultimately, that is the period during life when people are feeling independent, free of pain and free of disability. Because we can do that now in mice. The question is, can we get that to people? Wow, so being a part of this whole symposium, what is something that you're going to take back with you to your work at the Mayo Clinic? Well, there are a lot of perspectives here. There are a lot of interesting areas that I know nothing about that I need to learn about. And so I've heard of those things. There are friends here that I work with and it's nice to be updated on what their work is like and to see them and meet with them. And these kinds of meetings are always an opportunity to develop collaborations. So you can imagine that the basic biology of aging affects everything. So it's good to find people who are working in specific areas that might be impacted by the biology of aging that we can work with where they've got expertise in that particular condition. We've got arguably some degree of expertise in understanding what aging is and how to target it. And so working together with groups like that will help to hopefully speed progress in this field so that we can try to reduce the burden of disability in the population.