STEM-Talk

Today’s interview is with Dr. Abraham Morgentaler, an internationally known pioneer in men’s sexuality and the founder of the first comprehensive center in the U.S. specializing in men’s health. Abe’s research has upended longstanding concepts regarding testosterone therapy, prostrate cancer and male sexuality.  He is particularly credited with research that has contradicted the established view that testosterone injections led to elevated risks for prostate cancer. In today’s interview, we talk to Abe about testosterone deficiency and its effects on men’s health and sex drive; the biological functions of testosterone; and Abe’s work treating metastatic prostrate cancer. Abe is the director of Men’s Health Boston and an associate clinical professor of Urology at Harvard Medical School. He is the author of “Why Men Fake It: The Totally Unexpected Truth About Men and Sex,” which was retitled “The Truth About Men and Sex” for the paperback edition. He also is the author of “Testosterone for Life: Recharge Your Vitality, Sex Drive, Muscle Mass and Overall Health.” Show notes [00:02:58] Dawn opens the interview mentioning that Abe grew up in Canada, asking him what his interests were as a kid other than hockey. [00:04:28] Dawn asks what Abe’s gap year between high school and college was like. [00:07:48] Abe explains that when he was born, his mother had some specific wishes for him. He failed at one but came through on the other. [00:08:17] While a sophomore in college trying to find his way, Abe ended up studying sex hormones in lizards. [00:16:32] Dawn explains that for a long time the greatest fear related to the use of testosterone therapy was that it would lead to prostate cancer. This was based on a 1941 paper by Charles Huggins from the University of Chicago, who wrote that his research found cancers were sensitive to hormonal manipulation. Dawn asks Abe to discuss how he started questioning this long-held dogma that high testosterone levels caused prostate cancer. [00:23:29] Dawn mentions that this story is a great example of why it is important in science to question things, particularly the status quo. [00:31:50] Abe talks about his 2006 paper, “Testosterone and Prostate Cancer, a Historical Myth,” which showed that the data contradicted the old belief that more testosterone would lead to more prostate growth. [00:40:10] Ken mentions that Abe followed up his previously mentioned paper with another one titled, “The Saturation Model and the Limits of Androgen-Dependent Growth.” [00:45:19] Abe talks about the exciting work he is doing helping men deal with metastatic prostate cancer. [00:51:32] Dawn explains how Abe uses the term “low T” to describe a condition that is otherwise known as hypogonadism or testosterone deficiency syndrome. Abe describes the many biological functions of testosterone. [00:53:27] Abe responds to the criticism that because testosterone levels decline with age, the process must be natural and, therefore, should not be treated. [00:55:42] Abe discusses a paper that came out in 2013 in the Journal of the American Medical Association that reported increased cardiovascular risk in men given testosterone replacement, and how the study’s statistical analysis was seriously flawed. [01:07:03] Ken mentions that in 2017, a trial by Budoff et al., published in JAMA, suggested that testosterone replacement therapy in men with low T led to more rapid progression of atherosclerotic plaques compared to placebo. [01:13:21] Ken asks why Abe thinks that testosterone replacement therapy can actually be protective in regards to cardiovascular disease. [01:14:19] Ken asks about the seemingly rapid drop in testosterone levels in men in the western world as reported by several papers including the Massachusetts Male Aging Study, as well as a large Finnish Study, and a 2017 meta-analysis. [01:17:37] Dawn mentions that while most people are aware of the term menopause, most are less familiar with the term andropause, coined as the male equivalent. [01:20:41] Abe explains why blood tests for low T can be deceiving, and alternative tests that produce more practical results. [01:25:55] Dawn asks about Men’s Health Boston, which Abe founded in 1999, which was the first comprehensive men’s health center in the United States. [01:29:18] Ken asks about the different modes and types of testosterone administration. [01:33:21] Ken asks about the fears of the aromatization of testosterone to estrogen with replacement therapy. [01:36:14] Ken asks if there are any studies looking into “super physiological” levels of testosterone, such as levels up to 2000. [01:39:22] Ken mentions that in Abe’s book “The Truth About Men and Sex,” Abe explains that his attempt was to pull back the curtain to reveal men as they truly are, the last chapter being titled, “Men Are People, Too.” [01:43:19] Dawn asks Abe what he likes to do in his spare time. [01:45:36] Dawn mentions that Abe was 18 when he entered Harvard as a freshman, and asks him if he had any idea that he would still be at Harvard more than four decades later.

Our guest today is Dr. Adam Konopka, an assistant professor in the Department of Kinesiology and Community Health at the University of Illinois Urbana Champaign, who believes that aging is the greatest risk factor for just about every single chronic disease that exists. Adam’s lab, called the Musculoskeletal Aging and Metabolism Lab, is focused on aging-related research. In addition to doing research that looks at different ways to delay the onset of age-related diseases and functional decline, Adam also has done a lot of research related to the interaction of exercise with metformin. Adam and his colleagues had a paper in Aging Cell that suggested metformin may blunt the health benefits of exercise in healthy older adults, a study that attracted a lot of attention and was highlighted in a story in The New York Times back in June. Show notes: [00:03:59] Dawn opens the interview mentioning that Adam’s lab is at the University of Illinois, and asks if he decided on Illinois because he grew up in a suburb outside of Chicago. [00:04:28] Dawn asks Adam how he ended up getting into competitive swimming. [00:05:13] Adam explains how his involvement in swimming increased his curiosity about physiology and ways to improve performance, a line of thought that contributed to his eventual majoring in exercise science. [00:05:49] Dawn asks Adam why he decided to minor in entrepreneurship. [00:06:18] Dawn asks Adam about the time when a professor doing research in pediatrics gave Adam the opportunity to volunteer for a study. [00:07:01] Ken mentions that while Adam was a student, he had the opportunity to work on a study which looked at an exercise program used by crew members aboard the International Space Station. Adam explains what his role in this study was. [00:08:05] Adam talks about his time spent at the Mayo Clinic as a postdoctoral research fellow, where he focused his time on looking at skeletal muscle mitochondrial function. [00:09:00] Dawn explains Adam’s notion that mitochondria contribute to obesity induced insulin resistance, a highly debated topic. Dawn goes on to mention Adam’s 2015 paper that looked at obese women who had defects in mitochondrial efficiency and hydrogen peroxide emissions. Adam explains how exercise effectively restored the mitochondrial physiology of these women to that of a leaner phenotype. [00:10:36] Adam discusses a metformin study he was a part of while at the Mayo Clinic, where he tested a hypothesis that had been previously shown in cell culture, to learn if those findings were translatable to humans. [00:11:51] Adam talks about the significance of his findings that metformin improved fasting and postprandial glycemia without inhibiting glucagon-stimulated glucose production. [00:12:59] Ken asks about the two and a half years Adam spent at Colorado State and the research that he conducted there. [00:13:32] Adam explains the mission of, and the research being done at, his lab, The Musculoskeletal Aging and Metabolism Lab, at the University of Illinois. [00:16:25] Ken asks Adam if he has looked into rapamycin and muscle, with respect to mTOR inhibition. [00:17:01] Dawn mentions that Adam took these earlier studies, as well as the research he did as a postdoc, and started asking questions related to the interaction of exercise with metformin. [00:17:30] Ken mentions how this research led to Adam’s paper earlier this year, which was highlighted in the New York Times, and which cast doubt on the idea that exercise and metformin, both of which have been looked at in the context of healthspan extension, work well together in conjunction. [00:19:24] Dawn asks if the negative effects of metformin documented in various studies are relatively modest and or negligible. [00:20:30] Ken asks Adam to speculate on some of his findings, particularly why a certain portion of individuals dosed with metformin are likely to be negative-responders, but at the same time others are positive-responders. Adam talks on this wide variability in the response to metformin. [00:23:12] Dawn asks about Adam’s follow-up research into exercise and metformin that he received a grant for. [00:25:20] Ken mentions it has been suggested that people space out the taking of metformin from the time a person exercises, given that the half-life of metformin is six hours. [00:27:03] Dawn asks if the widely reported health benefits of metformin are worth it possibly inhibiting beneficial mitochondrial adaptations to exercise in older adults. [00:28:38] Dawn asks for Adam to speculate on the mechanisms behind how metformin blunts the adaptive response to exercise. [00:30:48] Ken talks in regards to the NIH-funded trial into metformin called, “Targeting Aging with Metformin” or TAME. Ken asks about Adam’s paper in GeroScience titled, “Taming Expectations of Metformin as a Treatment to Extend Healthspan.” [00:32:57] Ken mentions that he would have liked to have seen rapamycin used instead of metformin in the TAME trial. [00:33:42] Dawn asks if Adam believes that a metformin trial in healthy individuals is currently warranted. [00:34:38] Dawn mentions that while metformin undoubtedly helps individuals suffering from metabolic disease, it is unclear if it has any significant positive effects on already healthy individuals. She goes on to mention that this is paradoxical in light of the fact that the majority of popular interest in off-label use of metformin is in healthy individuals or the so called “worried well,” people who already follow habits of good health. [00:36:16] Ken asks Adam how, in a perfect world, he would design a trial for healthspan-extending intervention in regards to what intervention would he pick, and how he would gauge efficacy considering that an intervention in healthy individuals would ideally need to be continued for several decades in order to determine a true effect. Ken goes on to ask what the pros and cons are of proxies for age in such a study including telomere length as well as biological and epigenetic clocks. [00:39:26] Ken asks how Adam would adjust for lifestyle behaviors like dietary manipulation and exercise that activate similar pathways to drugs like metformin and rapamycin in his hypothetical study. [00:40:44] Dawn asks if Adam has much expectation in extending lifespan with pharmacological methods, or if he thinks that merely healthspan will increase while we see a so-called compression of morbidity, and if he thinks that these pharmacological treatments are likely to surpass lifestyle interventions like exercise. [00:42:39] Ken asks if Adam has looked at PPAR-D agonists, which are a class of drugs that provide some of the effects of exercise pharmacologically. [00:43:50] Adam gives his advice to people interested in extending their healthspan. [00:44:57] Dawn asks what Adam’s diet and exercise routine look like. [00:46:11] Dawn mentions that she knows that Adam and his wife have a young child and closes the interview asking Adam what he does for fun in his spare time. Links: Adam Konopka bio Musculoskeletal Aging and Metabolism Lab Facebook page Learn more about IHMC STEM-Talk homepage  Ken Ford bio Dawn Kernagis bio  

Today we talk with Dr. Rachel Yehuda whose pioneering research on cortisol and brain function has revolutionized worldwide our understanding and treatment of post-traumatic stress disorder. Rachel is also well-known for her studies on the intergenerational transmission of trauma and PTSD. This novel research has shown that the children of traumatized parents are at risk of similar problems due to epigenetic changes that are transmitted from the parents to their offspring. She has worked with war veterans, Holocaust survivors and other victims of trauma to detail the biological roots of PTSD. She is a professor of psychiatry and neuroscience and the director of the Traumatic Stress Studies Division at the Mount Sinai School of Medicine in New York City. She also is the director of the Mental Health Patient Care Center at the James J. Peters VA Medical Center. Show notes: [00:02:31] Dawn begins the interview asking Rachel about her time as a child growing up in Cleveland. [00:03:17] After Ken mentions that Rachel’s father was a rabbi, Rachel explains how growing up in an observant Jewish household shaped her. [00:04:46] Rachel talks about a biology teacher who inspired her to go beyond her interests in philosophy and pursue science. [00:05:50] Dawn asks Rachel why it seems that so many scientists start out with an interest in philosophy. [00:07:16] Dawn asks Rachel why she decided to major in psychology at Touro University in New York. [00:08:16] Ken asks Rachel why she decided to attend the University of Massachusetts at Amherst after graduating from Touro University. [00:09:03] Rachel explains how she went into graduate school looking for a way to become both a psychologist and a scientist. [00:10:08] Dawn asks Rachel about something Rachel’s daughter observed about her: “You move to the beat of your own drum. You never do anything other than what the voice in your head tells you to do.” [00:11:12] Ken asks if it is true that Rachel’s first graduate advisor was not optimistic about Rachel making it through grad school. [00:12:33] Rachel tells the story of how she first met Bill Edell and walked up to him and said that she wanted to do clinical research. [00:14:38] Ken asks Rachel why she decided to do research on stress, particularly when stress wasn’t a major focus of research in the 1980s. [00:16:05] Dawn mentions that after graduating from UMass Amherst, Rachel did her postdoctoral work in biological psychiatry at Yale Medical School. Rachel met Dr. Earl Giller there, who became Rachel’s mentor and an early researcher in post-traumatic stress disorder. Rachel talks about how Dr. Giller had just completed a study on Vietnam veterans showing low cortisol levels. [00:18:40] Rachel talks about how for her post-doc at Yale she wanted to look into the biology of personality, but was told that it was a “dumb idea” for post-doc research. [00:22:06] Dawn asks about the paradox uncovered by Dr. Giller’s research into Vietnam veterans showing low cortisol levels when stress is supposed to be associated with elevated cortisol levels. Dawn goes on to ask how this finding led Rachel to interview Holocaust survivors in her hometown of Cleveland. [00:24:43] Rachel tells the story of when she talked to a group of Holocaust survivors, a woman came up to her and said: You know, Dr. Yehuda, we don’t have VA centers like your veterans do. [00:26:20] Ken asks about the program Rachel set up to help Holocaust survivors. [00:27:20] Dawn points out that in 2016 Rachel published the results of a study looking at the genes of 32 Jewish women and men. She and her colleagues at Mount Sinai studied Holocaust survivors who either had been interned in Nazi concentration camps during World War II or had witnessed or experienced torture. Rachel also looked at the genes of 22 children who were born to the Holocaust survivors after the war. Rachel discusses how the changes in the DNA of Holocaust survivors were in a way passed down to their offspring. [00:29:13] Rachel discusses the necessary caution we should take regarding our understanding of mechanisms and how effects get from one place to another, or from the experience of one generation into the biology of the next, because we simply don’t have sufficient human studies that can truly pinpoint what truly causes the effects we see. [00:32:06] Ken asks about Rachel’s realization that past effects could transform not only the narrative of a person’s life but also their physiology. [00:33:59] Dawn describes Rachel’s 2005 study with woman who were pregnant in the World Trade Center during 9/11, which showed, along with other studies, that children of traumatized parents are at risk of having similar problems as their parents due to changes occurring in the biology of the parents as a result of trauma exposure. Dawns asks about the process of epigenetic changes being transmitted to offspring, which has become known as “intergenerational transmission.” [00:36:27] Ken asks if cortisol is uniformly low, or if there is substantial variation from person to person, since one often hears of elevated cortisol levels in first responders and military populations. [00:38:43] Ken asks Rachel how she ended up at Icahn School of Medicine at Mount Sinai. [00:39:40] Ken asks about Rachel’s role as the founder and director of the Division of Traumatic Stress Studies at Mount Sinai. [00:41:20] Dawn asks Rachel to describe what happens inside a person’s body when they find themselves in a stressful situation. [00:42:47] Dawn mentions that in psychiatry and mental health, symptoms of trauma are treated as psychological, but that Rachel is finding that these problems of trauma also correlate to people having physical problems. [00:44:02] Rachel talks about her role as the Director of the Mental Health Patient Care Center at James J. Peters Veterans Affairs Medical Center in the Bronx, which she has inhabited since 2009. [00:44:58] Rachel is asked to talk about how there are only a few approved pharmacological treatments for PTSD, and no approved medications to enhance resilience. [00:46:38] Ken asks about a study Rachel published in 2013 which indicated that effective psychotherapy can be thought of as a form of “environmental regulation” which is able alter a person’s epigenetic state. [00:49:36] Ken asks how Rachel thinks the discovery of the epigenetic inheritance of trauma could change the way we approach and treat chronic health conditions, and if it is possible that much of what we are experiencing in terms of physical and mental illness as a society at large could be manifestations of trauma that has been caused by changes to epigenetic memory. [00:51:09] Rachel describes her excitement about MDMA-assisted psychotherapy for PTSD, an interest she is collaborating on with Dr. Dave Rabin, who was interviewed on STEM-Talk episode 99. [00:52:14] Dawn refers the MDMA study that Rachel and others are collaborating on with Dave, and how this study has started its phase III trial with the FDA. Rachel gives an overview of what is going on with this study and how MDMA could be licensed and become a medicine. [00:56:09] Ken asks Rachel about her quote where she said in an interview, “My career has been enhanced by the fact that early on nobody believed in PTSD. Well, now, I almost think we’ve been a victim of our own success in many ways because I think we’ve ended up really pathologizing it to a large extent.” [00:58:37] Ken comments on how he relates to Rachel, in that his early career saw him also studying something believed to be impossible, AI, and that things have now been reversed and the power of AI is often overestimated. [00:59:45] Rachel explains that she is thankful to have become a scientist, even though she enjoyed philosophy in her youth, but that if she could no longer be a scientist for some reason, she would want to become a musician. [01:00:15] “Dawn mentions that Rachel has some experience appearing on stage as a singer, such as when she performed at the Meeting of the International Society of Psychoneuroendocrinology with colleagues Thomas Neylan  and David Spiegel (interviewed on STEM-Talk episode 45).  The song Rachel sang was titled “The Grant Song,”  Dawn closes the interview asking Rachel if she wrote the humorous lyrics. Rachel Yehuda bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Dawn Kernagis bio      

Today’s episode marks the 100th episode of STEM-Talk and the return of guest Peter Attia, who Ken and Dawn interviewed for episode one of STEM-Talk back in 2016. Peter is the founder of Attia Medical, a medical practice with offices in San Diego and New York City that focuses on the applied science of longevity. Peter emphasizes nutritional biochemistry, exercise physiology, sleep physiology, lipidology, pharmacology and four-system endocrinology to help people increase their lifespan and health span. Peter is the host of the podcast The Drive. He earned his M.D. from Stanford University and holds a B.S. in mechanical engineering and applied mathematics. Show notes: [00:04:44] Dawn opens the interview welcoming Peter back to the show. Dawn mentions that a lot has happened since she and Ken last interviewed Peter and points out that Peter is in the process of writing a book. [00:05:51] Ken asks Peter if it’s true that he does his best writing on long flights. [00:06:21] Dawn mentions that in 2014 Peter created Attia Medical, which is a practice with offices in San Diego and New York City, where he focuses on the applied science of longevity and optimal performance. Peter gives an overview of his practice and how he works to improve people’s healthspan and lifespan. [00:07:29] Ken asks Peter to explain the difference between a strategy and a tactic in the domain of optimization of performance and healthspan. [00:10:35] Dawn mentions that back on episode one of STEM-Talk that Peter talked about his eight drivers of longevity. Dawn asks Peter if his thinking over the past three years has changed in terms of the eight drivers. [00:12:30] Dawn asks what are some of the best lab tests in terms of longevity that people should request from their primary care physician. [00:14:25] Ken asks how Peter goes about determining optimal reference ranges to target in his patients, noting that the guidelines constituting normal are based on a sick overall population. [00:17:26] Dawn talks about how every year a new secret to longevity comes out with the force of hype behind it, but that rarely does the new so-called secret deliver. In contrast, she mentions how Peter encourages people to keep things simple and focus on nutrition, exercise and sleep. Peter explains how these three things can have the biggest impact on a person’s physical health. [00:19:35] Dawn explains that optimizing health span can be expensive, often costing upwards of $100,000 a year in tests and devices and off-label medications. She asks if Peter has any thoughts on if there is becoming a class divide in the world of healthspan and lifespan. [00:21:10] Ken explains that a primary inhibitor of BDNF is HDAC, and BHB is a powerful inhibitor of HDAC, which leads one to think that one of the mechanisms of exercise to increase BDNF is the elevation of BHB. [00:22:21] Ken mentions that the area under the curve for insulin is one of Peter’s favorite longevity markers, and asks him to talk about the concept of insulin area under the curve.  In addition to blood tests and glucose monitoring, Ken asks Peter what would be the next item of greatest interest in terms of longevity markers. [00:24:28] Dawn mentions that Peter wears an Oura Ring to monitor his sleep, and a glucose monitor to measure his blood sugar in real time. Dawn asks Peter to talk about the benefits of continuous monitoring versus short-term use for the purpose of building future behavior. [00:25:54] Dawn asks if Peter uses any other wearables besides the ones she just mentioned. [00:27:45] Dawn points out that Peter traveled to Easter Island with some friends, including David Sabatini, a guest on episode 70 of STEM-Talk. Dawn asks Peter to talk about the trip which was set up to explore first-hand the place where a group of Canadian researchers first discovered rapamycin. [00:29:13] Ken mentions that Peter is on record saying, “For me personally nothing is more interesting than rapamycin.” Peter explains what he has been learning about rapamycin and why it is so fascinating. [00:31:49] Ken says that in one of Peter’s podcasts, Peter mentioned he had been taking 5 mg of rapamycin. Ken asks what it was that informed that choice. Ken also asks Peter how he has been tracking rapamycin’s effects, and if he has any thoughts for listeners considering rapamycin. [00:33:38] Dawn asks if we are any closer to being able to accurately measure biological signals, such as mTOR activity and autophagy, than we were three years ago. [00:36:28] Peter explains his thoughts on muscle loss and fasting, and the amino acids that are important in muscles affected during a fast. [00:38:44] Ken mentions that there are a lot of misconceptions about protein consumption, particularly in the context of ketogenic diets. He mentions Valter Longo’s opinion that a diet high in protein is as bad as smoking. Peter explains his thoughts on the role of protein in health and performance. [00:41:05] Ken makes the point that the strongest viewpoints in science that have the most passion and anger behind them are often the ones with the largest error bars. [00:41:35] Dawn mentions the importance of IGF-1 and its related molecules on metabolism. She asks about the paradox when it comes to IGF-1 in terms of performance and longevity. [00:43:39] Ken mentions that the Annals of Internal Medicine published a study that made the point that eating red meat poses minimal health risks. Peter gives his thoughts on this. [00:48:39] Ken states that in addition to rapamycin and fasting, he and Peter share an interest in sauna, a practice with growing evidence for its benefits. Ken asks Peter’s opinion on the difference between infrared and traditional sauna. [00:50:03] Dawn mentions that in 2016 the Dong et al paper in Nature suggested that the limit of human longevity has been reached, and that Barbi et all published a paper in Science in 2018 that said that the mortality curve for humans flattens out once the age of 105 is reached. Peter shares his thoughts on just how long humans can live. [00:53:29] Ken mentions that a recent study from the Miller Lab suggested that metformin might inhibit mitochondrial adaptation in older adults, and that an even more recent paper out of the University of Kentucky and the University of Alabama reported that metformin significantly blunts muscle hypertrophy in response to resistance training. Peter gives his thoughts on this and why he stopped taking metformin. [00:55:36] Peter shares his concerns about generic metformin, as well as his recent interview with Katherine Eban about the fraud in the generic drug industry. [00:57:15] Ken mentions that Peter is a proponent of fasting, and is involved with the Zero app. Ken asks if the benefits of fasting can be thought of in relationship to ApoB levels. [00:59:18] Ken asks Peter to describe what he sees as the most interesting question he doesn’t yet have an answer to, but believes is eventually possible to know. [01:00:28] Dawn ends the interview by asking Peter if there is one thing that he did not believe three years ago that he now thinks is likely to be true. Links: Peter Attia bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Dawn Kernagis bio  

Dr. David Rabin is the chief innovation officer and co-founder of Apollo Neuroscience. He also is the co-inventor of Apollo, a wearable device designed to improve focus, sleep and access to meditative states by gently delivering layered vibrations to the skin. Dave is a board-certified psychiatrist and translational neuroscientist who for the past decade has been studying resilience and the impact of chronic stress on humans. He received his MD in medicine and Ph.D. in neuroscience from Albany Medical College in Albany, New York. He trained in psychiatry at Western Psychiatric Institute and Clinic at the University of Pittsburgh Medical Center. Dave also has organized the world’s largest controlled study of psychedelic medicines and is well-known for his research into MDMA and its potential to treat post-traumatic stress disorder along with other disorders. Show notes [00:03:06] Dawn opens the interview mentioning that David grew up in California and asking him about an insatiable need he had as a child to understand why people were the way that they were. [00:04:18] David talks about how the vivid and frequent dreams he had as a child played a role in his decision to study consciousness and neuroscience. [00:07:33] Dawn mentions that in high school Dave told his father that he wanted to study consciousness; however, Dave’s father suggested that he study something more tangible and quantifiable instead. Dave explains how this led him to spend the summer between his junior and senior year of high school at Rockefeller University. [00:12:08] Ken asks why Dave decided to move across the country to Albany Medical College, where he received his MD in medicine and Ph.D. in Neuroscience. [00:14:01] Dave gives an overview of the research he did, while working on his Ph.D., in emotional salience and how people interpret different stimuli as either threatening or safe. An area of research informed by his reading of evolutionary psychology, and the study of touch as an evolutionarily conserved stimulator of the safety pathway. [00:17:58] Ken asks about how Dave decided to go into psychiatry at Western Psychiatric Institute and Clinic at the University of Pittsburg Medical Center, where he focused on treatment-resistant mental illnesses. [00:20:47] Dawn mentions Dave’s work with Greg Siegel. Dawn asks about this work and how it led Dave to become serious about studying consciousness, altered states of consciousness, and the potential use of these altered states to facilitate healing. [00:24:26] Ken talks about MDMA, or 3,4-Methyl​enedioxy​methamphetamine, a psychoactive drug commonly known as ecstasy or molly.  He explains that MDMA has been shown to facilitate the release of oxytocin, which increases levels of empathy and closeness while dampening fear-related amygdala activity. This results in an overall decrease in stress response and social anxiety. Ken asks Dave to talk about MDMA’s potential to treat PTSD (posttraumatic stress disorder) along with other disorders. [00:27:37] Ken asks if Dave has seen any improvements in heart rate variability (HRV) post MDMA treatments. [00:28:37] Dawn mentions that Dave is part of the world’s largest controlled study of psychedelic medicines. She goes on to explain that these medicines, like LSD and MDMA and even psilocybin, which comes from mushrooms, were used to treat mental and emotional trauma from the 1950s to the ‘70s.  Due to the abuses that occurred during this time, the use as well as research on psychedelic medicines in U.S. were shut down. With a shift towards a renewed interest in these medicines, Dawn asks about this study and if Dave could give a background on psychedelic medicine. [00:32:34] Dave talks about the epigenetic trial, being conducted in phase three of the MDMA study, where DNA samples are collected before and after use, to determine the epigenetic regulation of stress-response genes. [00:41:30] Ken asks about psilocybin, which is a naturally occurring psychedelic produced by more than 200 species of mushrooms. Ken asks Dave to explain how psilocybin is different from MDMA, both chemically and experientially. [00:45:45] Dave discusses the use of ecstasy and the debate around the safety of MDMA, and how compared to stimulants such as cocaine, amphetamine and methamphetamine, addiction to MDMA is very rare. [00:48:47] Dawn explains that psychedelics are, to this day, illegal in the U.S., and further states that STEM-Talk is not advocating the use of these or any illegal substances, before asking Dave about the changing legal status of psychedelics. [00:49:51] Dawn asks about the use of cannabidiol (CBD) for management of symptoms for illnesses such as PTSD and pain-management. [00:54:17] Ken mentions that Dave has spent the last several years developing a technology called Apollo, which is intended to help people make changes more effectively. Given the research and study Dave has done into stress, meditation and athletic performance, and why some people are more resilient than others, Ken asks Dave what he has learned from all this and how it led to the Apollo technology. [00:57:31] Ken asks if the hypervigilance people have to text alerts and emails and phone vibrations and news alerts and the constant bombardment of noise and stimuli is conditioning our bodies to be in a hyper-stressed state all the time. [00:59:26] Ken asks how to retrain the nervous system to become more balanced between our sympathetic and parasympathetic symptoms without the use of psychedelics. [01:02:37] Dawn asks about cognitive patterns and the way people think about their lives, such as the tendency to take challenges personally and think “why me?” while others tend to see challenges as an opportunity for growth. [01:05:35] Dave talks about heart-rate variability (HRV) and why he considers it one of the more important findings about resilience that has been made in the past 15 years. [01:09:19] Dawn asks what a good range for HRV is, or if there is a significant degree of variation across healthy people. [01:10:31] Dave explains the Apollo wearable device in depth, and how and why it works. [01:11:57] Ken asks if there have been pilot studies with children for the Apollo device. [01:14:14] Dawn mentions that Dave’s wife Kathryn was the one who came up with the idea to create the company Apollo Neuroscience. Dave tells the story behind that. [01:15:37] Ken mentions that David and Kathryn are in in the process of launching Apollo, and that the devices will start shipping in January. [01:15:50] Dawn asks, given Dave’s study of stress and the pervasiveness of technology in our modern world and its role in our levels of stress, how he deals with stress on a day-to-day basis. [01:18:12] Dawn mentions that Dave went to work for his wife this last year and asks, aside from their working relationship, what the two of them do for fun. Links: Dave Rabin bio Learn more about IHMC STEM-Talk homepage  Ken Ford bio Dawn Kernagis bio  

Our guest today is Dr. Steven Austad who studies virtually every aspect of aging. He is a distinguished professor and chair of the Department of Biology at the University of Alabama, Birmingham. In addition to being recognized for his aging and longevity research, Steve is also well-known for his background as a New York City cab driver, newspaper reporter and a lion trainer who then decided to become a biologist. His research today involves developing lifestyle and pharmacological approaches to improving and preserving human health. He is particularly focused on figuring out why different species age at different rates. Steve is the author of more than 190 scientific articles. His book, “Why We Age: What Science Is Discovering about the Body’s Journey Through Life,” has been translated into nine languages. He also writes newspaper columns and has written for publications like Natural History magazine, Scientific American and International Wildlife. Show notes: [00:02:53] Dawn opens the interview mentioning that Steve was born in Southern California, but that his family moved around so much, that he ended up attending around 20 grade schools. Steve explains that his father bought a travel trailer and moved the family around the country. [00:03:57] Steve talks about how even though he was shy and introverted as a kid, he found a way to fit in with his classmates. [00:04:40] Ken mentions how Steve’s career went through several reinventions before settling into a career in science. Among the various occupations Steve had were: a newspaper reporter, training lions and tigers for television and movies, and taxi driving. Ken asks Steve how he became a taxi driver. [00:06:01] Steve talks about his time on the West Coast in Portland working as a newspaper reporter for the Oregonian. [00:07:48] Dawn asks how it was that Tippi Hedren and Melanie Griffith had something to do with Steve becoming a lion trainer. [00:14:39] Ken asks Steve about the suicidal duck whose reckless abandonment nearly resulted in Steve’s death at the hands of one of the lions he was training. [00:19:21] Steve discusses why his fascination with animal behavior lead him to California State University to major in biology. [00:23:24] Dawn asks what took Steve to the University of New Mexico for his postdoc. [00:28:16] Ken asks how Steve landed his job as assistant professor in the Department of Organismic and Evolutionary Biology at Harvard University in 1986. [00:29:59] Dawn mentions that Steve discovered that opossums of the predator-free barrier island of Sapelo Island lived 25 percent longer than their cousins on the mainland of Georgia. Steve discusses this and explains how this discovery played a role in his future research. [00:34:13] Dawn points out that Steve left Harvard for the University of Idaho where he became a full professor and then next went the University of Texas. Dawn asks Steve about accepting  a position in 2014 at the University of Alabama, Birmingham. [00:41:32] Steve discusses his research into lifespan and healthspan and longevity and why some species age at different rates, with a particular interest in long-lived organisms like quahogs clams and hydra. He goes on to explain how this research led to what he refers to as the “Longevity Quotient.” [00:48:42] Ken mentions that as a former Rhode Islander, he spent some time digging Quahogs and eating them. [00:53:14] Steve gives an overview of how dietary restriction studies are performed on mice. [00:59:39] Ken mentions that from Steve’s description it seems that modern humans are becoming more and more like laboratory mice. [01:02:53] Ken mentions STEM-Talk episode 79 where Satchin Panda talks about time-restricted eating, and episode 7 where Mark Matson talks about intermittent fasting. Ken goes on to say that Mark made the point that the benefits of time-restricted eating or intermittent fasting is that it puts the organism, particularly the human, in a state of ketosis. [01:04:09] Steve talks about the differences in the maximum lifespans of males and females in both humans and other animals. [01:08:42] Ken recommends STEM-Talk episode 67 with Doug Wallace for listeners interested in hearing more about mitochondria. [01:09:44] Dawn asks about metformin, which is a drug that many people believe has the potential to increase our healthspan and lifespan. She asks why it is that we’re not all taking metformin and if it really has such potential. She further asks about the status of the Targeting Aging With Metformin (TAME) trial. [01:13:39] Ken mentions a recent study coming from the Miller lab, that suggested metformin might inhibit mitochondrial adaptations to exercise in older adults. He goes on to mention an even more recent paper out of the University of Kentucky and the University of Alabama, Birmingham has reported that metformin blunts muscle hypertrophy in response to resistance exercise training in older adults. Ken also mentions Steve’s continued interest in rapamycin and its effect on the health span of animals. Ken asks what Steve has learned and if rapamycin would still be his first choice for testing for a drug to target aging. [01:20:08] Ken asks about the optimal and most efficacious dose of rapamycin for humans. [01:21:10] Dawn mentions a paper Steve co-authored with Tuck Finch, discussing the role of the different APOE isoforms. Dawn asks about the ancestral isoform and why we see different isoform distributions today compared to hundreds of thousands of years ago. [01:24:59] Dawna asks why we see different isoform distributions between different populations around the globe. [01:26:29] Dawn asks how much of a role lifestyle versus genetics plays in healthspan and lifespan. [01:28:58] Steve talks about of Fauja Singh, who is 108 and didn’t start distance running until he was in his 80s, and who ran a marathon when he was 101. [01:32:17] Ken asks if Steve is still as confident as he was in 2016 when he made a bet with Olshansky over whether there will be one or more 150-year-old human by the year 2150. [01:34:15] Ken asks why we haven’t seen someone exceed Jeanne Calment’s record age of 122 years that she reached in 1997. [01:36:04] Dawn mentions that Steve continues to write articles and columns for newspapers as well as other news outlets. In addition to this Steve also has a website called, “Let’s Talk Science?” where an assortment of his newspaper columns and other writings can be found. [01:37:47] Dawn closes the interview suggesting that Steve might want to explore writing a novel about a young newspaper reporter who ends up driving a Mercedes across California with a lion in the backseat, who then finds himself in a Hollywood mansion living with Tippi Hedrin and Melanie Griffin and watching over the lions and cheetahs that run through the house. Dawn suggests that has the makings of a good book. Links: Austad’s University of Alabama, Birmingham bio Let’s Talk Science Learn more about IHMC STEM-Talk homepage Ken Ford bio Dawn Kernagis bio

Our guest today is Francesca Rossi,  who for the past three years has been an AI Ethics Global Leader at IBM Research as well as an IBM Distinguished Research Staff Member. Prior to her time at IBM, she was a professor of computer science at the University of Padova, Italy. Francesca’s AI research interests include constraint reasoning, preferences, multi-agent systems, computational social choice, and collective decision making. Much of her research today is focused on the future of artificial intelligence and the ethical issues surrounding the development and behavior of AI systems. She is a fellow of both the worldwide association of AI (AAAI) and of the European Association of AI. She also has been president of the International Joint Conference on AI and the editor in chief of the Journal of AI Research. Sitting in for Dawn during today’s interview is IHMC colleague Brent Venable, who recently was named the inaugural director of a new Ph.D. program in Intelligent Systems and Robotics that is a partnership between IHMC and the University of West Florida. Brent is a graduate of the University of Padova and had Francesca as her academic advisor. Show notes: [00:03:25] Brent opens the interview asking Francesca where she grew up in Italy. [00:03:51] Brent mentions that Francesca was a curious child, who was fascinated with the moon landing. Brent asks what else Francesca was interested in as a child. [00:05:01] Francesca explains that if she were to stumble across a time machine she would be interested in going forward in time rather than backwards. [00:05:41] Ken asks why Francesca decided to study computer science in 1981when the field was relatively new. [00:07:22] Francesca discusses the one class in her academic career that stumped her, despite her good grades in every other subject. [00:08:36] Ken mentions that Francesca ended up in Austin, Texas after obtaining her degree in computer science, and asks what it was that lead her to the University of Texas and what research she did there. [00:11:40] Brent asks why Francesca decided to go back to Pisa after Texas to work on her Ph.D. [00:13:23] Brent mentions that after Francesca’s Ph.D., she moved to the University of Padova, where she worked for the next 20 years. Brent asks about the work that Francesca did in this period, particularly her seminal work on preferences for intelligent systems. [00:15:17] Ken discusses how Francesca became Brent’s academic advisor at Padova. Ken mentions that he has heard that the two of them had so much fun working together, that they did as much laughing as research during their time at Padova. He asks the two of them if that could possibly be true. [00:17:41] Francesca talks about the sabbatical she took to the Radcliff Institute. [00:22:00] Brent asks about an article in the Wall Street Journal that featured Francesca as well as a senior manager at IBM and one of the founders of Skype and how the article played a role in Francesca’s decision to move to the United States. [00:23:41] Francesca’s title at IBM is “Global Ethics Leader.” Brent asks Francesca to describe what the job entails. [00:30:00] Ken asks what Francesca envisions as the likely future of AI, and what she hopes for the future of AI. [00:31:54] Francesca discusses how we sometimes craft our visions for the future around our current technology, and that she believes that the proper approach should be to build our technologies around our visions for the future. [00:34:37] Brent asks Francesca for her thoughts on whether or not the fear of robots and AI going rogue and hurting people is a legitimate one, and what she thinks about the government adopting AI legislation. [00:38:23] Francesca gives her thoughts on the fears that AI will one day replace human workers. [00:41:43] Brent mentions that Matt Johnson, interviewed on episode 86 of STEM-Talk, had an article in AI magazine where he discussed human machine teaming, and said that humans and AI should work together the way two musicians do when playing a duet. [00:44:11] Ken asks about the current predominance of machine learning as opposed to traditional AI, otherwise known as symbolic AI, and if the area of preferences that Francesca has pioneered could be a potential candidate for bringing these two areas of AI together. [00:47:55] Brent asks if we ever decided to one day replace a judge with a deep learning algorithm, would AI be prone to discrimination based on the dataset that the deep-learning algorithm has been given to learn from. [00:52:35] Ken asks if there are ways to hold the people and the companies that design intelligent systems accountable for the decisions that they make? [00:55:29] Ken mentions that tech companies often shift blame to algorithms for mistakes that were a fault of humans whether intentional or unintentional. He asks about the growing concern of biases both consciously and unconsciously being imbedded into algorithms by the humans who make them. [01:00:34] In ascribing values to intelligent machines to abide by, Ken asks whose values should be used, as different cultures have different values as well as different ethical codes of conduct. [01:04:42] Brent asks about Francesca’s involvement with The Future of Life Institute, which leads Francesca to discuss Max Tegmark’s book “Life 3.0.” [01:08:11] Brent asks about another initiative Francesca is involved in called Partnership for AI. [01:10:52] Ken mentions that Francesca is the conference chair  for the 34th Annual AAAI Conference on Artificial Intelligence, which will take place in New York City in February. Ken asks what the submissions currently look like and also to talk about the health of the field. [01:13:49] Brent asks what Francesca does with her spare time. [01:15:11] Ken asks Francesca why he was told to reassure her that the STEM-Talk staff would use a photograph of her and not a photograph of “The Terminator” on the STEM-Talk home page next to her episode. Links: Francesca Rossi IBM bio Learn more about IHMC STEM-Talk homepage  Ken Ford bio Dawn Kernagis bio      

Today we have part two of our interview with Dr. Dickson Despommier, a microbiologist and ecologist who is the emeritus professor of public and environmental health at Columbia University. Today’s episode focuses on vertical farming, a concept that Dick and his students came up with in 1999. When Dick’s book “Vertical Farms: Feeding the World in the 21st Century” came out in 2010, there were no vertical farms in the world. Today, there are vertical farms throughout the U.S. and around the globe. Part one of our interview, episode 95, covered Dick’s nearly 30 years of research into intracellular parasitism and his focus on Trichinella spiralis, one of the world’s largest intracellular parasites. Dick is the author of five books, including “People, Parasites and Plowshares.” His most recent book, “Waist Deep in Water,” is a memoir of his life-long love of fly fishing, a topic we had so much fun discussing with Dick that we touch on it in today’s episode as well as in part one of our interview with Dick. Show notes: [00:02:08] Ken opens part two of our interview with Dick by pointing out that there were no vertical farms in the world when Dick’s book “The Vertical Farm: Feeding the World in the 21stCentury”came out in 2010. Ken asks Dick to give an overview of the idea behind vertical farms and also discuss how the idea gained momentum. [00:06:33} Dick explains how the students’ original concept of rooftop gardens evolved into the idea of growing plants inside buildings. [00:08:14] Dick talks about the growth of vertical farming since 2011 and how Japan is the country that has the highest number of vertical farms. [00:09:26] Ken describes a vertical farm located in the heart of Jackson Hole, Wyo., called Vertical Harvest. It’s a 13,500 square-foot green house that can grow produce that is equivalent to 10 acers of traditional farming. This vertical farm sells produce year-round, mostly to local restaurants and grocery stores, but also to individuals who want to go onsite to buy their produce directly. Ken asks if this is a good example of what Dick was hoping for when he conceived of the idea of a vertical farm. [00:13:16] Ken asks Dick to address the criticisms of vertical farming and how the cost of building these structures outweighs the advantages. [00:17:14] Dawn points out that Dick was named teacher of the year eight times during his time at Columbia and asks him for his thoughts about what it takes to become a good science teacher. [00:19:49] Dawn asks about Dickson’s recently published memoir about his love affair with fly fishing, titled “Waist Deep in Water.” [00:20:39] Dick talks about the literature professor that “Waist Deep” is dedicated to and how the professor inspired Dick to start writing. [00:22:07] Dickson tells the story of how he caught his first trout. [00:29:04] Ken ends the interview by asking about Dick’s favorite Shakespeare quote that Dick says gets to the heart of what really matters in life. Links: Dickson Despommier bio “The Vertical Farm: Feeding the World in the 21stCentury” https://www.verticalharvestjackson.com/our-mission “People, Parasites and Plowshares: Learning From Our Body’s Most Terrifying Invaders” The Living River website “Waist Deep in Water” Learn more about IHMC STEM-Talk homepage  Ken Ford bio Dawn Kernagis bio

Our guest today is Dr. Dickson Despommier, a microbiologist and ecologist who is the emeritus professor of Public and Environmental Heath at Columbia University.  Our conversation with Dick covered a variety of topics and ran so long that we divided his interview into two parts. Part one covers the nearly 30 years Dick spent conducting research on intracellular parasitism, especially Trichinella spiralis, one of the world’s largest intracellular parasites. Part two of our interview with Dick focuses on vertical farming. In 1999, Dick and his students came up with the idea of raising crops in tall buildings. When his book, “The Vertical Farm: Feeding the World in the 21stCentury,” came out in 2010, there were no vertical farms in the world. Today, there are commercial vertical farms not only throughout the United States, but also in Korea, Japan, China, England, Scotland, The Netherlands, France, Russia, Dubai, Canada and a host of other countries. Dick is the author of five books, including “People, Parasites and Plowshares.” His most recent book, “Waist Deep in Water,” is a memoir of his life-long love of fly fishing, a topic we had so much fun discussing that we touch on it in part one and part two of our interview with Dick. Show notes:  [00:03:40] Ken begins the interview by mentioning that he and Dawn are great fans of two podcasts that Dick helps co-host, “This Week in Parasitism”and “This Week in Virology.”  Ken points out that “This Week in Virology” launched in 2008, making Dick an early adapter of science-based podcasting. Ken asks Dick how he got involved in podcasting. [00:06:24] Dawn mentions that Dick was born in New Orleans, and that his parents moved across the country to San Francisco when he was only a year old. Dawn goes on to mention that as a kid Dick liked to play outdoors and collect pollywogs and dragonflies. Dick talks about how his mother encouraged him to bring home spiders and frogs and other specimens he collected on his outdoor adventures. [00:07:14] Ken mentions that when Dick was 11 his family moved again to New Jersey, asking how that came about. [00:09:06] Dawn asks about the beginning of Dick’s lifelong love of fishing that started when he was a child. [00:11:54] After Dick talks about recently spending 20 days in Wyoming, Ken and Dick begin a conversation about their favorite rivers in the state to go fishing. [00:13:57] Ken and Dick talk about their fishing bait of choice when they were kids: Wonder Bread. Ken goes on to ask Dick how his love of fishing also evolved into an interest and fascination with wading into creeks, streams and river beds. [00:14:56] Dick talks about his website “The Living River.” [00:16:39] Dawn asks about Dick’s experience with his high school biology teacher who recognized his curiosity and who played a pivotal role in shaping Dick’s scientific career. [00:20:26] Dawn mentions that Dick almost didn’t go to college, but that he eventually jumped in academics bigtime and earned a bachelor’s degree at Fairleigh, a master’s at Columbia, and his doctorate at Notre Dame. [00:22:29] Dawn asks about Dick’s experience during his postdoc at Rockefeller University where there were 12 Nobel prize winners who would sit down with him and ask questions about his research. [00:23:54] Ken asks Dick about his decision to return to  Columbia after his postdoc. [00:27:00] Ken mentions that Dick’s experience at Rockefeller cemented his approach to teaching. Ken asks Dick to talk about how when he returned to Columbia that he became as equally engaged in teaching as he was in research. [00:30:18] Dawn asks Dick about his extensive research into the parasite Trichinella spiralis, something Dick has described as “the worm that would be a virus.” [00:38:09] Dawn asks about Dick’s 1998 article for Parasitology Todayabout the Nurse Cell-Parasite complex of Trichinella spiralis, and how it is unlike anything else in nature. [00:47:19] Ken mentions that Emma Wilson, a researcher who has spent more than 15 years studying Toxoplasma gondii, was the guest on episode 93 of STEM-Talk. Ken asks Dick to discuss what is special about T. gondii. [00:51:28] Ken mentions that just recently researchers at the University of Wisconsin Madison have discovered why cats are the definitive host for Toxoplasma gondii. [00:55:33] Dawn asks about Dickson’s interest and research into ecotones, or the transition area between two biomes, a zone of high disease transmission that leads to the spread of schistosomiasis malaria and a variety of parasitic worms. [01:00:03] Ken asks about the prevalence of hookworm in the South following the Civil War and how eradicating it helped revive the Southern economy. [01:06:47] Ken points out that John D. Rockefeller and others thought they had noticed a certain malaise among many in the American South in the years after the war.  Rockefeller put together a commission that was comprised of luminaries across many disciplines who examined possible causes ranging from spiritual to social to psychological to medical. Ken asks Dick to elaborate on this interesting episode and explain how it was connected to Italian tunnel workers? [01:13:56] Ken ends part one of the interview with a humorous story about  how he dug through solid rock to build his family’s outhouse in Maine. Links: Dickson Despommier bio “The Vertical Farm: Feeding the World in the 21stCentury” “People, Parasites and Plowshares: Learning From Our Body’s Most Terrifying Invaders” “Waist Deep in Water” Learn more about IHMC STEM-Talk homepage  Ken Ford bio Dawn Kernagis bio    

Our guest today is Dr. John Newman, a geriatrician and researcher who is well-known for a 2017 study that found a ketogenic diet reduced the mid-life mortality of aging mice while also improving their memory and healthspan. John is an assistant professor at the Buck Institute for Research on Aging and a geriatrician in the Division of Geriatrics at the University of California, San Francisco. He also is a physician who works with older adults in the San Francisco VA Medical Center. At Buck, John studies the molecular details of how diet and fasting regulate the genes and pathways that control aging. He particularly focuses on the ketone body beta-hydroxybutyrate and how its molecular signaling activities involving epigenetics and inflammation regulate aging and memory in mice. Show notes: [00:02:51] Dawn opens the interview asking John what it was like growing up in Long Island. [00:04:20] Dawn mentions that John was described as a pretty geeky kid growing up, and asks him about his childhood. [00:05:40] Ken asks John if being the type of kid who would do all the homework in his textbooks in the first couple of months annoyed his classmates. [00:07:34] Dawn asks why John decided to go to Yale University. [00:08:45] Mentioning that Yale doesn’t have a pre-med program, Dawn asks what John decided to major in. [00:10:15] John explains how he met his wife at Yale. [00:11:28] Dawn asks John why he traveled across the country to the University of Washington after graduating from Yale. [00:12:26] Dawn asks why John decided to focus his graduate work on the progeroid Cockayne syndrome. [00:14:15] John discusses his decision to go to the University of California, San Francisco for his residency. [00:16:05] Dawn asks if John immediately joined the faculty at San Francisco after his residency. [00:17:03] Ken asks John about his work to improve the care of older adults and help them maintain their independence as they age. Ken asks for an overview of the work John and his colleagues do in this area at the Buck Institute [00:18:39] Ken mentions that a lot of John’s work focuses on the molecular details of how diet and fasting regulate the genes and pathways that control aging. Ken asks John to elaborate on this work. [00:20:04] Dawn asks what specifically attracted John to the idea of studying the ketogenic diet as an intervention in mid to later life as opposed to a diet consumed habitually throughout life. [00:23:12] Dawn mentions that John and Eric Verdin, who recruited John to the Buck institute, share an interest in looking at ketone bodies as signaling metabolites, a topic they have written about. [00:26:21] Ken talks about a conference he and Dawn attended on CBD and seizures, where Ken made the point that ketones are a metabolite of THC. [00:27:52] Ken asks John to go into more detail about how ketone bodies may link environmental cues such as diet to the regulation of aging. [00:29:08] Ken talks about how it seems clear that ketone bodies are emerging as crucial regulators of metabolic health and longevity via their ability to regulate HDAC (histone deacetylases) activity and thereby epigenetic gene regulation. He asks John to discuss how beta hydroxybutyrate may be an increasingly useful and important signaling molecule as we age. [00:34:24] Dawn mentions that John and his colleagues published paper in 2017 in Cell Metabolism titled “Ketogenic Diet Reduces Midlife Mortality and Improves Aging in Mice.” Dawn asks why John chose a cyclical rather than continuous ketogenic diet for this study. [00:37:56] Dawn asks why John decided to conduct the test of physiological function while the ketogenic diet group was off the diet, and on a standard high-carbohydrate diet. [00:40:02] Dawn mentions that Megan Roberts and her colleagues at theUniversity of California Davis were also conducting studies on the effects of a ketogenic diet on mice around the same time as John’s study, and that both were published in the same issue of Cell Metabolism. Dawn goes on to mention that Megan was recently interviewed on episode 92 of STEM-Talk where she discussed her paper,  “A Ketogenic Diet Extends the Longevity and Healthspan in Adult Mice.” Dawn adds that both Megan’s and John’s studies had similar findings but that Megan’s had the added caveat that the ketogenic diet may also improve strength and coordination. Dawn asks what John’s takeaways were from Megan’s paper and how do the two papers differ? [00:44:50] Ken mentions that he is personally looking at the effect of the ketogenic diet as a way to avoid sarcopenia and other aspects of aging. [00:46:42] John discusses possible reasons why the ketogenic diet has such pleiotropic effects on people suffering from diseases such as type 2 diabetes, epilepsy, inflammation etc. [00:50:17] Dawn mentions that one of the most frequent criticisms of the diet comes from nutritionists who say “show me the five-year data,” she asks how John would respond to that. [00:54:25] Ken asks about the “arctic variant” mutation, and how this mutant might affect ketosis. He asks John to describe the mutation and how he thinks it might be affecting ketone metabolism in the Inuit population, and how the scientific community might go about investigating this further. [01:00:06] Dawn asks if John has used exogenous ketones in his studies. [01:02:21] Dawn asks what the right overlap between the ketogenic diet and exogenous ketones is, and if exogenous ketones might be synergistic with the ketogenic diet. [01:04:17] Ken asks if there is a threshold or target blood level of ketones for people on the ketogenic diet and using exogenous ketones. [01:07:27] Ken mentions that another metabolite that has been shown to affect life span is alpha-ketoglutaric. Ken asks John to speculate as to if the mechanism of life span extension seen here is similar to BHB and if the two might be synergistic. [01:09:30] Dawn mentions that in addition to his work as a researcher at the Buck institute, John is also a geriatrician who cares for older adults who have been hospitalized at the San Francisco VA Medical Center. Dawn asks what sort of work John does with older individuals. [01:11:25] John discusses his perspective on the education and training of future geroscientists. [01:15:01] Dawn asks what the most promising interventions being investigated in geroscience are right now. [01:23:05] Dawn comments that John has been in the Bay area for more than 10 years, going on to ask if it is true that his main interests outside of work are volleyball baseball and food. [01:24:46] Ken ends the interview mentioning that a little birdie told him that John is a connoisseur of the San Francisco pastry-shop scene. Links: John Newman UCSF bio Newman Lab website John Newman ResearchGate profile Learn more about IHMC STEM-Talk homepage Ken Ford bio Dawn Kernagis bio