It’s time for another Ask Me Anything episode where STEM-Talk cohost Dawn Kernagis asks Ken questions submitted by listeners. In this episode, Ken and Dawn weigh in on: —  Whether AI is becoming sentient. — How women in midlife might protect their bodies from the negative effects of a slowing metabolism. — A Stanford study that compared a low-carbohydrate diet with a Mediterranean diet. — Whether fasting helps optimize cognitive performance. — The future of hypersonic technology. — And a lot more. If you have a question after listening to today’s episode or any episode of STEM-Talk, email your question to STEM-Talk Producer Randy Hammer at rhammer@ihmc.org. Show notes [00:02:45] Dawn begins the AMA with a question for Ken that was inspired by the Mark Mattson interview, episode 133. Mark talked about skipping breakfast and in his recent book,  “The Intermittent Fasting Revolution,” Mark points out that bodybuilders often skip breakfast and do their weight training in a fasted state, which has the effect of optimizing both muscle building and cognitive performance. The listener mentions that they feel more cognitively sharp in a fasted state but as soon as they break their fast, they don’t feel as sharp. The listener asks Ken if this is normal. [00:04:35] A listener asks Ken about a recent news story in which a Russian robot broke a boy’s finger during a chess match. The listener goes on to state that several of their friends have jumped to the conclusion that this is proof robots are becoming sentient beings and asks Ken for his take is on this given Ken’s AI background. [00:06:02] A listener asks another AI question, this one regarding the Washington Post’s reporting on a Google engineer who was fired over claims he made while at the company that an AI chatbot he had been testing had become sentient. The engineer claimed in an interview with The Guardian that the chatbot, LaMDA, was afraid of being turned off, had read “Les Miserables” and that it had emotions. Google maintains that LaMDA is merely responding to prompts designed for it. The listener asks Ken what would be an appropriate test for gauging AI sentience and what other thoughts Ken has about this story. [00:08:32] A listener mentions that they have been following the ketogenic diet for 18 months and have lost 40 pounds. Recently they checked their liver enzymes GGT, AST, TSH and found they were elevated above “normal” and their Alpha fetoprotein marker was measured at 10.3. The listener asks Ken what he has learned about the ketogenic diet’s impact on the liver. [00:09:48] A listener asks about a recent paper regarding a Stanford study that compared low-carbohydrate diets with a Mediterranean diet. The listener mentions that in the Stanford study the diets had three similarities – no non-starchy vegetables, no added sugars and no refined grains. The key difference in the diets was that the low-carb diet avoided legumes, fruits, and whole grains while the Mediterranean diet included them. The study measured glucose control and cardiometabolic risk in people with prediabetes and type 2 diabetes. The study found that comparative outcomes did not support a sufficient benefit to justify people avoiding legumes, whole fruits, and whole grains to achieve the metabolic state of ketosis. The listener asks Ken for his thoughts on the study and in his answer, Ken mentions an interview Dr. Ben Scher did with one of the study’s authors, Dr. Lucia Aronica. [00:14:57] A listener mentions in their question that they found the Mike Griffin and Mark Lewis interviews both fascinating and worrying. The listener’s key concern is that China and Russia are ahead of the U.S. in terms of hypersonic capabilities. The listener goes on to mention that they recently saw “Top Gun Maverick” and asks if it is reasonable that someday we will see jets with human pilots that are capable of flying 10-to-20 times the speed of sound, as depicted in the film; or will these sorts of aircrafts need to be operated by AI or humanoids. [00:18:17] A listener sends a question that reads, “They say that 50 is the new 30, but after listening to STEM-Talk, I now know that I can expect my metabolism to fall off the “50-cliff” once I meet the chronological milestone of turning 50 years old.”  The listener says it’s her understanding that hormonal changes related to midlife, especially for women, are key drivers of metabolic changes that lead to everything from brain fog to weight gain. The listener would like to know what she and other women can do to ward off the negative effects of aging and a slowing metabolism. [00:19:53] A listener mentions that in the Satchin Panda interview, Dr. Panda says that black coffee in the morning probably won’t break an overnight fast, but that coffee with cream will. The listener goes on to say that they listened to a Dave Asprey podcast in which he said drinking “Bulletproof Coffee” with two tablespoons of butter and two tablespoons of brain octane fuel was okay in the morning because it will elevate a person’s blood ketones to 0.7 millimoles per liter within 30 minutes. The listener asks Ken for his thoughts on this advice. [00:22:33] Dawn closes the AMA with a listener question asking if Dr. Ford has any particular pet peeves that he is willing to share. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Our guest today is Dr. Jason Fung, a Toronto-based nephrologist, and the best-selling author of “The Obesity Code,” “The Diabetes Code,” and “The Cancer Code.” Jason is best known for his success in combining a low-carb diet with intermittent fasting to help thousands of overweight patients reverse their type 2 diabetes, lose weight, and improve their metabolic health. Jason is the author of the blog “The Fasting Method” and the co-founder of the Intensive Dietary Management program, an initiative that provides low-carb dietary guidance and counseling on various fasting regimes. Jason is also the co-author with Jimmy Moore of “The Complete Guide to Fasting,” which looks at the history and culture of fasting and how it helps people improve their metabolic health. In today’s episode, Ken is joined by Visiting IHMC research scientist Dr. Tommy Wood and together, they and Jason discuss: How in the beginning of his practice, Jason prescribed insulin for type 2 diabetes patients. How a series of landmark studies starting in 2008 changed Jason’s mind about using glucose-lowering medication for type 2 diabetes. Jason’s realization that type 2 diabetes is largely a dietary disease and therefore requires a dietary solution rather than a pharmaceutical one. The origins of Jason’s Dietary Management program, which counsels overweight and obese patients to follow a low-carbohydrate, high-fat diet to reduce insulin. A critique of the “eat less, move more” strategy acclaimed by many obesity experts. Mark Mattson’s research into the powerful impact of intermittent fasting on metabolic health and a recent paper that questioned the effectiveness of time-restricted eating when compared to daily calorie restriction. Recent research and evidence that fasting during chemotherapy may reduce the side effects of the treatment. Show notes: [00:02:25] Tommy opens the interview mentioning that Jason was born and raised in Toronto and asks what drew Jason to science as a kid. [00:03:43] Tommy mentions the irony that Jason has written several best-selling books, yet Jason was not fond of English or writing when he was in school. [00:04:53] Ken mentions that after graduating from high school, Jason stayed close to home and attended the University of Toronto, entering into medical school just after turning 19 to study internal medicine, eventually specializing in nephrology. Ken asks Jason what intrigued him about becoming a kidney specialist. [00:06:36] Tommy asks Jason what led him to go to UCLA after medical school for his specialty training in kidney disease at Cedars-Sinai Medical Center. [00:07:37] Tommy mentions that Jason has been practicing clinical nephrology in Toronto since 2001, and that in those early years of his practice, Jason saw patients with type 2 diabetes and prescribed medications to keep their blood glucose low. When that didn’t work, he would prescribe insulin, which is the standard medical practice. Tommy asks what Jason observed during these early years of his practice. [00:09:28] Ken mentions that in 2008, two landmark studies were published, the ACCORD study and the ADVANCE study (a summary of ADVANCE). These studies were followed by two more studies, the ORIGIN and VADT studies, all four of which demonstrated that using blood glucose-lowering medication for type 2 diabetes didn’t necessarily have the expected benefits. Ken asks Jason to talk about how these studies were eye-opening for him and confirmed his own experience in treating patients. [00:16:27] Tommy explains that in 1972 Robert Atkins published the “Dr. Atkins’ Diet Revolution,” which shared his findings on the effectiveness of low-carb, high-fat dieting. Tommy goes on to mention that in the late 1990s, a string of Atkins-styled diet books surged in popularity, with most physicians being opposed due to the conventional wisdom that these high-fat diets would cause heart disease. As a result, several trials were launched in the early 2000s to prove this point. Tommy asks Jason to talk about how these trials revealed that the real story is more nuanced than people might think. [00:20:42] Ken mentions that even though Jason and countless other doctors were appalled at the notion that high-fat diets were being promoted as safe and effective, Jason and other physicians had virtually no nutritional training during their years in medical school. Ken asks if, in hindsight, Jason believes this is something that needs to change. [00:24:49] Tommy explains that Jason’s realization that type 2 diabetes was largely a dietary disease and therefore required a dietary solution rather than a pharmaceutical one led him, along with Megan Ramos, a medical researcher, to establish the intensive Dietary Management program in Scarborough, Ontario, in 2011. The object of this program is to counsel overweight and obese patients to follow a low-carbohydrate, high-fat diet to reduce insulin. Tommy asks about the results of this initiative. [00:28:56] Tommy points out that when when Jason started seeing positive results with his patients losing weight and getting off their medications with a high fat diet, Jason started giving lectures around Toronto. He  eventually posted a six-part lecture on the etiology of obesity on YouTube and starting a blog, “Intensive Dietary Management,” which evolved into “The Fasting Method.” This all received good feedback and opened the door for Jason to write a book, “The Obesity Code.” [00:30:43] Ken explains that Jason’s book begins with a critique of the “eat less, move more” strategy acclaimed by many obesity experts.  Jason points out in the book that while this sounds like a reasonable approach to weight loss, the approach has generally been ineffecitve. Ken asks Jason to elaborate on this. [00:37:08] Tommy explains that there is substantial experimental evidence that the “eat less, move more” approach is not particularly effective advice for individuals in an environment that promotes being sedentary while surrounded by hyperpalatable, calorie-dense, low-protein food. Tommy goes on to say that this does not imply that an integrated calorie balance model is incorrect, only ineffective. Tommy asks Jason for his thoughts. [00:46:58] Ken mentions that in Mark Mattson’s appearance on STEM-Talk, he talked about his recently published book, “The Intermittent Fasting Revolution: The Science of Optimizing Health and Enhancing Performance.” Ken goes on to say that in this interview Mark talked about a paper he had in the New England Journal of Medicine that highlighted how studies in animals and humans have shown that eating in a six-hour window and fasting for 18 hours has been shown to have positive effects on lifespan and a wide range of chronic disorders including obesity, diabetes, cardiovascular disease, cancers, and neurodegenerative brain diseases. However, a recent paper that appeared in the same journal reported that a year-long study among patients with obesity found that a regimen of time-restricted eating was not anymore beneficial – with regard to reduction in body weight, body fat, or metabolic risk factors – than daily calorie restriction. Ken asks Jason for his opinion on this recent study. [00:55:54] Ken mentions that Jason’s answer has circled back to efficaciousness versus effectiveness, and asks if Jason would agree that fasting is a more effective method than calorie restriction to lose weight because it is easier to follow. [00:57:52] Tommy asks if Jason agrees that calorie restriction is efficacious but not effective because it is hard for people to follow. [00:58:45] Tommy asks Jason about his third book in what has been referred to as the wellness series, “The Cancer Code.” [01:02:35] Ken explains that there is obviously a genetic aspect to cancer, but our environment also plays a huge role in the development of cancer. Jason points out in his book that a Japanese woman who moves from Japan to San Francisco often doubles and or triples her risk of cancer. Ken asks what makes the environment of the U.S. such a risk factor, and what makes the environment in Japan protective. [01:05:47] Ken mentions that there is also evidence that fasting during chemotherapy may reduce the side effects of the treatment. Ken asks Jason to talk about this and how fasting might also increase the efficacy of chemotherapy. [01:07:50] Tommy mentions that he understands that Jason weighs the same as he did in high school, and asks what his diet and fasting protocol look like. [01:11:15] To wrap up the interview, Ken  asks Jason for his take on rapamycin and concerns about the risk-reward ratio of using rapamycin as a prescription medication. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Tommy Wood IHMC bio Tommy Wood University of Washington bio Jason Fung  bio  

Today’s episode features the author of “Why We Get Sick,” Dr. Ben Bikman, a biomedical scientist at Brigham Young University. Ben is known for his research into the contrasting roles of insulin and ketones as key drivers of metabolic function. In “Why We Get Sick,” Ben takes a deep dive into insulin resistance and metabolic health. The book particularly focuses on the role that insulin resistance plays in many of today’s most common diseases: heart disease, diabetes, cancer, and Alzheimer’s. Ben and his colleagues at the Bikman Lab investigate the molecular mechanisms behind the increased risks of disease that accompany obesity and excess visceral fat. Much of the research at the Bikman Lab particularly focuses on the etiology of insulin resistance and how it disrupts mitochondrial function. In today’s interview, STEM-Talk cohosts Drs. Ken Ford and Dawn Kernagis talk to Ben about: How insulin resistance is tied to multiple chronic diseases. The relevance of ketones in mitochondrial function. How so many of our modern chronic diseases are self-inflicted and driven by insulin resistance. How many of the hallmarks of aging are a consequence of insulin resistance. The theory that the longest-lived people are likely the most insulin sensitive. The benefits that occur with carbohydrate reduction as a result of increasing insulin sensitivity. Ben’s thoughts about the degree of intermittent fasting needed to induce autophagy in humans. Show notes: [00:02:32] Dawn begins the interview asking Ben about his early life growing up in a small farm town in southern Alberta, Canada, as one of 13 children. [00:02:48] Dawn asks Ben what he was like as a kid and what made him stand out from his 12 brothers and sisters. [00:06:01] Dawn asks about Ben’s mother’s influence and how she wanted her sons to be Renaissance men. [00:08:29] Ken asks about Ben’s experience as a Church of Jesus Christ of Latter-Day Saints Missionary in Samara, Russia. [00:15:18] Dawn mentions that while Ben went into his undergrad majoring in exercise science, he wasn’t that interested in science at the time. It wasn’t until he began working on his master’s degree at BYU with Dr. Will Winder that he developed a true interest in science. [00:19:49] Dawn asks Ben how he ended up at East Carolina University for his Ph.D. in bioenergetics. [00:21:42] Ken mentions that Ben, after completing his Ph.D. moved to Singapore for his postdoc work at the Duke National University of Singapore. Ken asks how that came about. [00:25:49] Dawn mentions that Ben is well-known for his work on insulin resistance, stemming from his time at East Carolina when he realized that insulin resistance is tied to many different chronic diseases. Dawn asks what was Ben’s ah-ha moment that led him to focus his research on insulin resistance. [00:27:49] Dawn mentions that much of Ben’s work is focused on the role of elevated insulin in regulating obesity and diabetes, as well as the relevance of ketones in mitochondrial function. Dawn asks if it is correct that Ben has been on a sort of mission as a professor to teach a new generation of doctors and nurses how insulin resistance works, and why it is so relevant in terms of chronic disease. [00:29:56] Ken mentions that Ben began to take his message about insulin resistance beyond the classroom, appearing on podcasts and making YouTube videos, and also giving a speech to the student body at BYU, titled “The Plagues of Prosperity” making the case that the human race is currently eating itself into metabolic disarray. [00:32:31] Ben’s book “Why We Get Sick” points out that historicall, people got sic because of infectious diseases. In modern times, due to sanitation, vaccines, and antivirals, that is less of an issue. Today more people are afflicted by chronic illnesses, many of which are related to metabolism. Dawn explains that the overarching message of the book is that these diseases are, in part, self-inflicted, and partially driven by insulin resistance and hyperinsulinemia. Dawn goes on to say that while it is fairly well-known that insulin resistance plays a role in cancer, heart disease, and diabetes, many people may not know that it also contributes to neurological disorders, reproductive health, kidney disease, gastrointestinal disorders, and even reduced muscle mass, bone loss, and even hearing loss. [00:34:42] Ken explains that Ben has often pointed out that many of the hallmarks of aging are partially a consequence of insulin resistance. Ben has also pointed out in his book the theory that the longest-lived people are likely the most insulin sensitive. Ken asks Ben to elaborate on this. [00:41:36] Ken mentions that in Ben’s book, he explains that there are three primary causes of insulin resistance, the most obvious one being chronically elevated insulin levels. In addition to this, however, the second category is stress hormones including cortisol and epinephrine. The third cause is inflammation. Ken asks Ben to elaborate on these three causes. [00:45:15] Dawn asks Ben to talk about why our healthcare system has a glucose-centric view of metabolic health. [00:50:26] Ken points out that there’s a lack of consensus on what optimal levels of insulin should be. He also points out that most Americans do not have optimal levels of insulin since most are metabolically unhealthy. Ken asks Ben for his thoughts on what a person’s optimal level of insulin should be. [00:53:34] Ken brings up the problem with the reliance on “normal” readings since unhealthy people skew the average and therefore what is considered normal. Ken asks Ben to talk about how this leads to people who are ketogenic being flagged by their physicians because their insulin levels are low according to their charts. [00:59:25] Dawn asks Ben why he believes building and using muscle is a key component in the fight against insulin resistance. [01:01:03] Dawn mentions that Ben advises people to control carbohydrates, prioritize protein, and “fill with fat.” Dawn asks about the numerous benefits seen with carbohydrate reduction via increasing insulin sensitivity and lowering hyperinsulinemia. [01:03:55] Ken asks Ben to give a quick primer on the process of autophagy, with respect to intermittent fasting. [01:07:54] Ken mentions that a lot of the research about autophagy and fasting uses rodent models.  Autophagy is activated much more quickly and to a much greater extent in rodents than in humans. In light of that, Ken asks Ben if we know to what degree intermittent fasting induces autophagy in humans and how long a fast would have to be to incur that effect. [01:11:01] Ken asks Ben to explain how the standard American diet drives fat storage in the body and slows a person’s metabolic rate. [01:16:53] Dawn brings up that recent studies have shown that ketones are not only viable fuel sources for all cells with mitochondria but are also legitimate signaling molecules that elicit advantageous changes in inflammation, cognition, oxidative stress, and more. Additionally, ketones may be relevant metabolic fuel in the context of physical activity and athletic performance. Dawn mentions that further exploration of this can be found in episode 94 of STEM-Talk with John Newman on the topic of beta-hydroxybutyrate, or BHB, and episode 54 with Briana Stubbs on the topic of ketones and athletic performance. Dawn goes on to mention that in a paper published by Ben in 2018, in a special issue of the International Journal of Molecular Science, Ben wrote about the effects of ketones on metabolic function. He reported on the results of a study that sought to shed light on the specific effects of the ketone body BHB on muscle cell mitochondrial physiology. Dawn asks Ben to walk listeners through the results of this study and its implications. [01:20:54] Ken mentions that looking at the role of ketones on the maintenance of muscle, it appears that ketones have less of an anabolic role and more of an anti-catabolic role, which produces a strong protective effect against sarcopenia. Ben talks about this. [01:23:02] Ken mentions that we could make a serious dent in our obesity and type-2 diabetes epidemics if people would think more seriously about insulin and if more physicians tested for it. Ken asks Ben what research, in this regard, are he and his colleagues excited for on the near-term horizon. [01:27:03] Dawn shifts topics to ask Ben what his exercise routine looks like. [01:30:29] Dawn closes the interview by asking Ben if he still plays any instruments. Links: Ben Bikman bio Ben Bikman Lab Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio  

Our interview today is with Dr. Vyvyane Loh, a board-certified physician in obesity and internal medicine. She is the founder and leader of Transform Alliance for Health, a Boston preventive-care practice that  specializes in weight management and the treatment of chronic metabolic diseases such as diabetes, hypertension and dyslipidemia. She and her staff are known for helping people lose 50 pounds or more and getting their type-2 diabetic patients off their many medications. Vyvyane has spent her medical career developing expertise in immunology, metabolic syndrome, fat metabolism, clinical nutrition, and preventive medicine. In today’s interview, we discuss how abdominal, or visceral, fat is linked to a wide range of metabolic disorders. Vyvyane goes on to explain how there’s a clearcut association between obesity and decreased brain volume that rarely gets discussed. When her overweight patients complain about their behavior around food and how they consistently give in to snacks that patients know are bad for them, Vyvyane explains how the challenges they are facing is often a result of the brain struggling with decreased blood flow and the shrinkage of neurons. Vyvyane also shares how a patient asked Vyvyane if she knew anything about the Atkins diet, and although she didn’t, Vyvyane ended up doing the diet along with her patient. This led Vyvyane to start seriously researching whether a ketogenic diet could help people not only lose weight, but also reverse chronic disease. Toward the end of today’s interview, we explore Vyvyane’s interest in macrophages, which are specialized cells involved in the detection and destruction of bacteria and other harmful organisms. We also have a nice discussion about how Vyvyane took some time off from practicing medicine to enroll in the writing program at Warren Wilson College in North Carolina in 1999. She spent the next two years writing a novel, “Breaking the Tongue.”  Set in Singapore during World War II, her book was nominated for the prestigious International IMPAC Award in fiction and was selected by the New York Public Library as one of its top 25 books of 2004. If you are interested in finding out more about Vyvyane, check out her website, vyvyanelohmd.com. Also, Vyvyane launched a podcast this week, which you also can find on her website. Episode one looks at “Metabolism: What It Is, And How It Affects Your Health.” If you enjoy today’s interview with Vyvyane and the many other interviews we’ve had on STEM-Talk discussing the treatment and prevention of chronic metabolic diseases, you may want to check out the upcoming virtual conference on Targeting Metabesity. Our cohost Dr. Ken Ford will be one of nearly 70 speakers, including many former guests on STEM-Talk, talking about the growing evidence that the major chronic diseases of the day share common metabolic roots and as a result may also share common solutions. To find out more about the conference, follow this link to the Targeting Metabestiy home page where you find a program guide and list of speakers. If you would like a free ticket to the conference, click on this link where you will find instructions on how to receive a code for complimentary admission that is being offered to STEM-Talk listeners. Ken will be moderating a session on emerging research related to endogenous and exogenous ketosis in health and disease as well as the role of ketones in mild traumatic brain injury and the prevention and treatment of cancer. If you have enjoyed the interviews we’ve had on STEM-Talk with Drs Steven Austad, Colin Champ, James Kirkland, John Newman, Brianna Stubbs, Jeff Volek and Morley Stone, who are all speaking at the conference as well, you should find the talks by the over 70 speakers quite interesting and beneficial. So, click here to request a free registration and we will make sure to send a you a code for a complimentary ticket. Show notes [00:04:45] Dawn mentions that, based on the interviews she’s listened to with Vyvyane, that writing and dance have been passions of hers since she was a child. Dawn then asks Vyvyane at what point did she become interested in science. [00:05:25] Dawn asks Vyvyane how she ended up in the states attending Boston University. [00:06:25] Ken asks why Vyvyane decided to double major in biology and classics. [00:08:14] Ken mentions that Vyvyane’s classics advisor has a connection to the town of Seaside, near where IHMC is located. [00:09:01] Dawn shifts topics to talk about Vyvyane’s research, and asks about TOFI, which stands for “Thin Outside, Fat Inside.” It refers to people who outwardly appear thin, but have a disproportionate amount of adipose tissue in their abdomen, as well as “normal weight obesity.” [00:10:58] Ken mentions that the TOFI phenomenon helps to highlight the relative lack of utility of BMI, which is just a function of the relationship between a person’s height and weight, meaning that people with TOFI will look fine in terms of BMI, and someone who is lean and muscular may be categorized as obese by BMI, particularly if they are not very tall. Ken asks Vyvyane to elaborate on this. [00:12:26] Dawn explains that abdominal, or visceral, fat is of particular concern because it’s a key player in a variety of health problems, more so than subcutaneous fat. She goes on to explain that visceral fat is found deep within the abdominal cavity, where it pads the spaces between our organs. Dawn asks Vyvyane to talk about how visceral fat is linked to a wide range of metabolic disorders. [00:14:37] Ken explains that obesity often causes endothelial dysfunction, which results in the vasculature being inflamed and damaged, resulting often in decreased blood flow to the brain. Ken asks Vyvyane to talk about her frustration with the fact that this clearcut association between obesity and decreased brain volume rarely gets discussed. [00:17:22] Dawn mentions that it is estimated that just 12 percent of Americans are categorized as metabolically healthy. She goes on to mention that researchers at the University of North Carolina published a study that found that just one in eight American adults have optimal metabolic health. [00:18:22] Ken asks Vyvyane what she has learned about metabolic disease in her practice that she didn’t learn in medical school or her residency. [00:19:10] Dawn asks about the prevalence of using food to relieve stress in the wake of the COVID-19 pandemic, and what effects of this trend Vyvyane has seen in her practice. [00:20:13] Ken asks about Vyvyane’s practice, which she started in 2015 because she had been working in the medical system and came to the realization that she couldn’t develop a new way of providing preventive care from within the system. [00:21:53] Dawn mentions that Vyvyane’s practice is called the Transform Alliance for Health, and the website is quoted as saying: “Chronic stress and emotional issues commonly lead to using food to self-medicate or self-soothe. The visible result, the patient’s weight, becomes the focal issue for their healthcare providers. For us, however, it is merely the physical manifestation of the patient’s internal struggle with his/her real problem. From this starting point, we work with our patients to uncover their deeper and often more complex reasons for overeating and to take charge of their lives.” Vyvyane elaborates on this approach to her practice. [00:23:29] Dawn mentions that she listened to an interview with Vyvyane where she talked about how a ketogenic diet can often reduce inflammation and reverse metabolic disease, but that it can be hard to get people to stick to a ketogenic diet. Dawn asks if this is why Vyvyane emphasizes going on a low carb diet for her patients rather than a strict ketogenic diet. [00:25:07] Ken asks about the struggles of having to convince patients to give up carbs. [00:27:17] Dawn explains that non-alcoholic fatty liver disease is today one of the most common maladies in the United States, with a remarkable 30 to 40 percent of adults in this country having it. Dawn asks Vyvyane to discuss NAFLD and what she sees as its causes and the most efficacious treatments. [00:29:07] Dawn asks about the markers Vyvyane uses in evaluating a patient’s metabolic health, including insulin resistance scores and advanced lipid panels. [00:31:45] Ken asks about the curriculums Vyvyane offers for her patients, which explain to them the importance of sleep and mobility and strength training as a way of pressing the body’s “the reset button.” [00:34:00] Dawn mentions that we recently had Greg Potter and Jeff Iliff on the podcast to talk about the importance of sleep and particularly how a lack of sleep can lead to many negative health outcomes. Dawn goes on to mention that something Vyvyane has emphasized in the past is the role of nocturnal blood pressure dipping during sleep. Dawn asks Vyvyane to explain what she means by that, and how a lack of it increases a person’s risk for silent strokes and kidney dysfunction. [00:35:45] Ken asks Vyvyane to talk about her recommendations for protein intake as it relates to body composition and sarcopenia. [00:39:18] Ken asks Vyvyane to talk about some of the immune cells that are involved in regulating metabolic health. [00:41:34] Dawn mentions Vyvyane’s recent lecture at IHMC, titled “On the Magical Mystery Macrophage Tour, where she refers to macrophages as mysterious, specialized cells of innate immunity that play significant roles in some of our most common medical conditions ranging from cardiovascular disease to gastrointestinal disorders to obesity to osteoarthritis. Vyvyane elaborates on what these cells are and their various functions. [00:43:02] Ken asks how and when Vyvyane first became interested in macrophages. [00:43:41] Ken mentions that macrophages also stand out because they possess the unique ability to become polarized in response to different environmental stimuli and asks Vyvyane to explain how this works. [00:46:22] Dawn explains that macrophages can detect products of bacteria and other microorganisms using a system of recognition receptors such as toll-like receptors or TLRs. Vyvyane explains the role and significance of these receptors. [00:48:13] Dawn mentions that tissue-resident macrophages, or TRMs, are heterogeneous populations originating either from monocytes or embryonic progenitors and distribute in lymphoid and non-lymphoid tissues. Dawn asks Vyvyane to talk about the diverse roles that TRMs play in many physiological processes, including metabolic function. [00:50:46] Ken mentions that current medical practice still looks at obesity through the lens of caloric balance. Ken asks what new discoveries in obesity research challenge that dogma. [00:54:39] Dawn asks about the aspects of Vyvyane’s life outside of her medical practice such as writing, dance, and choreography. [00:55:47] Ken mentions that Vyvyane’s novel, “Breaking the Tongue,” was selected as one of the Top 25 Books of 2004 by the New York Public Library and in 2006 was nominated for an International IMPAC Award, which is the world’s richest prize for a single work of fiction published in English. Ken explains that the novel chronicles the fall of Singapore to the Japanese in World War II, and asks Vyvyane to talk about the book and how it deals with issues of race and class. [00:58:08] Ken mentions that Vyvyane has another novel she is working on, but that it, and her fiction writing as a whole, is on hold because she is working on a nonfiction book. Ken asks Vyvyane to talk about this new book. [00:59:47] Dawn closes the interview asking about Vyvyane’s morning routine, which incorporates an hour of meditation. Dawn also asks what else Vyvyane does on a regular basis. Links: Vyvyane Loh bio Vyvyane Loh podcast Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio    

Our guest today is Dr. Jeffery Iliff, a professor of psychiatry and behavioral sciences in the Department of Neurology at the University of Washington. Much of Jeff’s research focuses on neurodegeneration and traumatic brain injury. He is the associate director of research at the VA Puget Sound Health Care System and a co-leader for research at the University of Washington’s Alzheimer’s Disease Research Center. In this episode, we talk about Jeff’s investigations into the glymphatic system, which is a newly discovered brain-wide network of perivascular spaces that facilitates the clearance of waste products from the brain during sleep. Jeff goes on to describe how he is exploring how the glymphatic system fails in the aging brain as well as in younger brains after traumatic brain injury. Jeff and Dawn also have a conversation about their collaboration on a research project  that’s focused on how extreme stressors impact the glymphatic system. Together they are investigating a potential approach to optimizing glymphatic clearance for individuals with acute or chronic sleep deprivation. Show notes: [00:02:55] Dawn opens the interview asking Jeff where he grew up. [00:03:21] Dawn asks what Jeff what he was like as a kid. [00:04:01] Ken mentions that it wasn’t until Jeff was working as a lifeguard at a boy scout camp that he first became interested in science. Ken asks Jeff what it was about his lifeguard experience that triggered the interest. [00:05:06] Dawn asks what led Jeff to the University of Washington as an undergrad. [00:06:02] Ken mentions that Jeff originally intended on going into pre-med. Ken explains that Jeff changed his mind and asks about a suggestion from a girlfriend that caused Jeff to have a change of heart. [00:07:39] Dawn points out that in addition to working in the lab as an undergrad, Jeff also worked a 48-hour shift as an EMT over the weekends. Dawn asks Jeff why he kept such a busy schedule. [00:09:35] Ken asks what led Jeff to the Oregon Health & Science University for his Ph.D. [00:10:53] Dawn asks if it’s true that Jeff’s wife played a big role in his decision to travel across the country to New York for his post-doc at the University of Rochester. [00:13:06] Dawn mentions that after the second year of Jeff’s post-doc, he was promoted to a junior faculty position because he was part of the team that discovered a brain cleaning system known as the glymphatic system. The team published a paper in 2012 in science translational medicine that was the first of about ten papers that later became known as the “glymphatic papers.” After a follow-up paper in 2013, Science Magazine cited the discovery that the glymphatic system cleans the brain during sleep as one of the “Top 10 Breakthroughs of 2013.” Dawn asks what this experience was like for Jeff as a young post-doc and junior faculty member. [00:15:55] Dawn explains that the lymphatic system is a network of vessels extending throughout most of the body that transport excess fluid and waste from the interstitial spaces between cells to the blood. She goes on to explain that these vessels are notably not found in the brain leading to the question of how interstitial fluid is cleared in the brain. Jeff’s team discovered the glymphatic system, which serves the same function in the brain as the lymphatic system in the rest of the body. This discovery turned out to be a paradigm shift and led to numerous subsequent studies. Dawn asks Jeff how the initial 2012 study came about and how they identified a distinct clearing system in the brain that serves a lymphatic function. [00:19:59] Dawn mentions that after Jeff’s initial work in the glymphatic system, he went on to write what has become known as his sleep paper. Dawn goes on to say that for this study, Jeff used two-photon microscopy to visualize fluid moving in and out of the brain, and at some point, saw his tracer leaving the brain. Dawn asks Jeff what this experience was like. [00:23:55] Ken asks Jeff to explain the relationship between sleep cycles and the glymphatic system. [00:26:33] Jeff explains some of the differences in sleep between mice and humans. [00:28:35] Ken asks if the critical role of slow-wave sleep in glymphatic function and clearance explains the potential relationship between sleep deprivation and increased risk of neurodegenerative disease. [00:31:29] Ken asks about the impact of sleep deprivation of normal cognitive function. [00:32:43] Ken asks if there is any research on the glymphatic function of APOE4 carriers. [00:35:33] Ken asks about work done by Jeff’s postdoc mentor, Maiken Nedergaard, that suggests that glymphatic function can even be impacted by sleep that is outside the normal circadian rhythm, potentially explaining the increased risk of neurodegenerative disease in shift workers. [00:38:50] Dawn mentions that Jeff’s 2013 sleep paper became the predecessor for many subsequent neuro-imaging studies looking at glymphatic function in the human brain, leading to the pursuit of new neuro-imaging techniques for the measurement of glymphatic function and asks about the developments in this area. [00:42:36] Ken asks about Jeff’s 2014 paper in the Annals of Neurology, in which he proposed that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with the accumulation of misfolded protein aggregates. [00:46:44] Ken asks if there is thought to be a connection between glymphatic function and other disorders like Parkinson’s, vascular dementia, etc. [00:48:45] Dawn asks about the meningeal lymphatic system, which consists of lymphatic vessels running parallel to the dural venous sinuses and middle meningeal arteries, and how it relates to the glymphatic system. [00:52:01] Ken asks Jeff why he thinks the glymphatic system had not been identified until recently. [00:54:48] Ken asks about Jeff’s move from the University of Rochester back to Oregon, and how Phil Knight, founder of Nike, played a role in this decision. [00:56:14] Dawn mentions that Jeff was at Oregon for six years, but during this time became connected with a research group at the VA Puget Sound Health Care System in Seattle, which is an affiliate of the University of Washington. Dawn asks what led Jeff to return to Washington, where he currently works as a professor in the Department of Neurology and is the Associate Director for Research at the VA Center, as well as what he and his research group are currently studying. [01:00:24] Ken asks how traumatic brain injury (TBI) affects the glymphatic system. [01:02:44] Dawn mentions that in TBI, Aquaporin-4, or AQP4, is a water channel expressed in astrocytes throughout the central nervous system as well as in epithelial cells in various peripheral organs. The expression of this protein changes in the setting of TBI. She goes on to explain that AQP4 is involved in brain water balance, neuroexcitation, astrocyte migration, and neuroinflammation and is the target of pathogenic autoantibodies in neuromyelitis. Jeff’s 2017 paper in JAMA Neurology looked at how altered AQP4 was associated with aging brains. Dawn asks about this paper, and the implications that the loss of perivascular AQP4 localization may be a factor that renders the aging brain vulnerable to the misaggregation of proteins in neurodegenerative conditions such as Alzheimer’s. [01:05:30] Dawn mentions how the collaboration between her and Jeff’s teams involves working on several studies involving human glymphatic imaging in different settings. Dawn asks Jeff to explain the efforts in validating a non-invasive contrast-free imaging approach to visualizing glymphatic function in humans. [01:08:30] Ken asks Jeff to explain why validating new imaging approaches against intrathecal contrast MRI is so important for the clinical and research communities. [01:12:06] Dawn explains that the first study she and Jeff officially started working on together is funded by the Office of Naval Research, and kicked off in 2021. In this study, they are assessing the impact of extreme environmental conditions on glymphatic function in humans, ranging from hypoxia, hypercapnia, and hyperoxia. Dawn asks Jeff to talk about the status of these studies and their impact on future human glymphatic research. [01:16:28] Dawn asks about a paper Jeff and his team published on astronaut brains post-flight and whether fluid-filled spaces in the brain, known as perivascular spaces, are enlarged post-flight. [01:19:41] Dawn mentions that one of the biggest questions she gets about the glymphatic system is if it can it be ‘fixed’ to function better if it has been impaired. Dawn asks Jeff how he would answer this question based on the current state of research. [01:21:46] Dawn asks Jeff if there are any nutritional or exercise approaches that might help improve glymphatic function. [01:22:53] Ken asks if Heart Rate Variability (HRV) plays a role in glymphatic function. [01:24:52] Dawn mentions that her and Jeff’s collaboration has expanded to include Dr. Miranda Lim at Oregon Health and Science University, Dr. Don Tucker at the Brain Electrophysiology Lab, and Dr. Jeffrey Heys at Montana State University. They are working on DoD funded study to look into a device that could potentially stimulate the glymphatic system in individuals who are acutely or chronically sleep deprived. [02:27:10] Ken asks what should the next key studies in glymphatic research focus on. [01:29:29] Dawn asks if Jeff still takes time off from his lab work to go watch his son’s baseball games and his daughter’s softball games. [01:30:22] Ken asks if it’s true that Jeff is a huge fantasy football fan, and that when he was a post-doc fellow, he and some colleagues started a fantasy football league that is still going on all these years later. [01:32:15] Dawn says she assumes Jeff is a Seattle Seahawks fan and asks Jeff if he ever had Russel Wilson on his fantasy football team. [01:33:15] Ken asks if it is true that Jeff’s students are fans of STEM-Talk. [01:34:19] Dawn closes the interview telling Jeff to let his students know to write a review of this episode so they can get a free STEM-Talk t-shirt.

Today we would like to introduce you to one of our newest colleagues here at IHMC,  Dr. Kaleen Lavin, a research scientist who investigates the molecular mechanisms by which the body adapts and reacts to stressors such as exercise, training and aging. Kaleen came onboard at IHMC last year and is known for her use of computational biology techniques as a means to understand and improve human health, performance and resilience. She also is interested in the use of exercise as a countermeasure for a range of disease conditions, including neurodegenerative diseases such as Parkinson’s disease. Today we will talk to her about some of her most recent work that examined the molecular effects of exercise training in skeletal muscle and in people with Parkinson’s. We also talk to Kaleen about her recent paper that took a comprehensive look at the current literature surrounding the molecular and cellular processes underlying the molecular benefits that exercise induces in humans. The paper appeared earlier this year in Comprehensive Physiology and was titled, “State of Knowledge on Molecular Adaptations to Exercise in Humans.” Kaleen is a graduate of Georgetown University, where she earned a bachelor’s degree in biology. She also earned a master’s in sports nutrition and exercise science from Marywood University in Pennsylvania and a Ph.D. in human bioenergetics from  Ball State University in Indiana. Show notes: [00:03:02] Dawn opens the interview mentioning that Kaleen grew up in Scranton, Pennsylvania, and asks Kaleen about her passion for music as a youth. [00:03:25] Ken asks Kaleen about her high school years and how she became  a competitive swimmer. [00:04:26] Dawn mentions that Kaleen was an excellent student growing up, but that it wasn’t until her junior year of high school that she became interested in science. Dawn asks if it were a teacher who inspired Kaleen. [00:05:21] Dawn asks what led Kaleen to attend Georgetown University after graduating from high school. [00:05:57] Dawn asks if Kaleen knew she wanted to major in biology when she first arrived on campus at Georgetown. [00:06:45] Ken asks about Kaleen’s experience of becoming a part of the Howard Hughes Program at Georgetown, which led to her gaining experience working in lab. [00:08:47] Dawn mentions that Kaleen transitioned from competitive swimming to running during her undergraduate years, running a marathon and half marathon. Dawn asks if  Kaleen’s father, who is an avid marathoner, gave her the incentive to start signing up for marathons. [00:13:19] Dawn asks Kaleen about a faculty advisor who noticed her passion for running and exercise and helped her decide what to pursue for her master’s degree. [00:15:23] Ken asks Kaleen what led her to pursue her master’s at Marywood University, a small Catholic University in Scranton. [00:16:56] Ken asks Kaleen what prompted her to pursue a Ph.D. in exercise science at Ball State University, which has one of the longest-standing human performance programs in the country. [00:17:57] Dawn mentions Kaleen’s experience with no-breath laps as part of her training when she was in high school on the swim team. Dawn asks Kaleen to explain what no-breath laps are. [00:19:00] Dawn asks Kaleen about a study she conducted for her master’s thesis at Marywood that examined the effects of controlled frequency breath swimming on pulmonary function. [00:22:13] Ken asks about how Kaleen’s time at Ball State set her up for her post-doc work at Center for Exercise Medicine at the University of Alabama at Birmingham. [00:24:31] Ken asks what it was about UAB that attracted Kaleen to do her post-doc work there. [00:26:08] Dawn asks about a study published in 2017 by a group at UAB led by Marcas Bamman where researchers took people with Parkinson’s disease and ran them through a high-intensity exercise program, finding that you could not only help people preserve some function but also restore some function. [00:28:52] Ken mentions that despite the awareness of Parkinson’s negative impact on motor function, there has been very little attention paid to its impact on skeletal muscle. Ken asks Kaleen to talk about her study that provided insights into the potential mechanistic roles of skeletal muscle. [00:31:33] Dawn mentions that the research Kaleen just discussed was published in a paper titled “Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease.” [00:31:51] Kaleen talks about her analysis of the dataset from the 2017 study at UAB that was led by Marcus Bamman.  Kaleen explains how she was able to identify 706 genes that were differently expressed after rehabilitative training, and how this work strengthens our understanding of skeletal muscle as a communicative tissue in exercise, aging, and neurodegenerative disease. [00:33:38] Dawn asks Kaleen to elaborate on how she ended her paper talking about how future research is needed to determine the influence of exercise training on other levels of phenotypes in Parkinson’s Disease and how skeletal muscle may reflect or orchestrate these changes. [00:35:31] Ken asks Kaleen to talk about her plans for a future clinical trial concerning Parkinson’s at IHMC. [00:37:21] Dawn asks about another study Kaleen conducted that looked at why people respond differently to the same exercise. Dawn also asks Kaleen to talk about why the reduction in skeletal muscle mass with advancing age is such a serious issue. [00:39:20] Ken follows up mentioning that sarcopenia is often thought of as a gradual decline in muscle mass, but often it is a process where there will be a slow gradual trend punctuated with large downward spikes as individuals grow older and experience illness and injury over the years. [00:41:01] Ken mentions that for the aforementioned study, Kaleen examined what occurs at the molecular level to shed light on the impact of resistance training on muscle hypertrophy. Ken goes on to explain that, previously, the UAB lab and others had demonstrated the magnitude of resistance-training-induced muscle hypertrophy is highly variable across individuals, a phenomenon known as interindividual response heterogeneity. [00:43:07] Dawn mentions that Kaleen used two algorithms to assess the evidence of gene networks that link muscle building to gene expressions. Dawn asks why Kaleen decided to proceed this way, and what future research possibilities does this method open up. [00:45:20] Ken asks about the possibility that Kaleen’s study leaves open the idea that exercising in the past leaves a molecular footprint, creating a kind of “muscle memory” that can come back to help us as we age, even if we haven’t kept up the habit of exercise. [00:54:39] Dawn mentions that Kaleen’s 2019 study on the effects of aging and lifelong aerobic exercise on inflammation supports other recent evidence that training is anti-inflammatory. Kaleen explains that the lifelong habit of exercise offers protection against “inflammaging,” which is the experience of chronic low-grade inflammation throughout the aging process. Dawn asks, however, if people who have waited till their 30s or 40s to begin the habit of exercise have passed the window of opportunity to benefit from the protective therapeutic factors that regular training confers. [00:55:55] Dawn explains that Kaleen was recently the lead author of a paper that appeared earlier this year in Comprehensive Physiology titled, “State of Knowledge on Molecular Adaptations to Exercise in Humans.” Dawn explains that this paper was a comprehensive look at the current literature surrounding the molecular and cellular processes underlying exercise-induced benefits and adaptations in humans. Dawn asks Kaleen to explain how the study of exercise as a preventative and therapeutic treatment has been rapidly gaining momentum for the past couple of decades. [00:57:58] Dawn mentions that the National Institutes of Health decided to fund a trial to look at the effects of exercise at the molecular level across a large group of people to build what they’re calling the Molecular Map of Exercise. Dawn asks Kaleen to talk about the consortium that the NIH is funding for this trial, and how Kaleen’s paper ties into that. [01:01:46] Ken asks what kind of response this review paper has received from the broader community. [01:02:49] Ken mentions that Marcas Bamman, who is helping spearhead IHMC’s new Healthspan, Resilience and Performance Complex, recruited Kaleen to become part of this initiative. Ken asks Kaleen what attracted her about this project. [01:04:15] Dawn mentions that Kaleen is heading up a lot of the computational work at IHMC to help the institute’s researchers gain insight into why some people respond better to exercise than others on a molecular level. Dawn goes on to mention that Kaleen is currently working on a number of ongoing projects and asks her to talk about how her work plays into all this research. [01:05:44] Kaleen talks about how it’s essential to have the right tools as researchers’ questions become more complicated. She and a colleague at IHMC recently received funding to enhance what is known as a pathway-level information extractor, a tool more commonly referred to as PLIER. Kaleen talks about how the funding for this project will allow IHMC to build up its algorithm potential and open the door for IHMC researchers to handle higher dimensions of data.   [01:07:48] Dawn asks about a paper by a group of researchers out of the Swedish School of Sport and Health Sciences in Stockholm, which examined acute molecular responses to concurrent exercise involving different muscles. [01:09:56] Ken asks if Kaleen thinks that her type of muscle fiber, which is highly skewed toward Type I, has anything to do with her gravitation towards endurance sports [01:11:39] Ken talks about the shift in muscle fiber type seen in the aging population where fast twitch fibers are lost first, leading to some older people maintaining strength but losing explosive power. [01:13:20] Dawn asks if there is a triathlon in Kaleen’s future. [01:14:02] Dawn asks Kaleen about the influence of muscle-fiber type on performance and how that might influence someone in terms of them gravitating toward a particular mode of exercise. [01:15:41] Dawn closes the interview asking about Kaleen’s passion for singing and how she now sings in her church choir. Links: Kaleen Lavin bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio  

In response to several requests from listeners, we have as our guest today, Dr. Matt Kaeberlein, a professor of pathology at the University of Washington. Matt is well-known for his investigations into the basic mechanisms of aging. Much of his research in this area is focused on identifying interventions that promote healthspan and lifespan. In today’s interview, we talk to Matt about the biology of aging and what he has learned about slowing the aging process.  In 1999, Matt and his colleague Mitch McVey discovered that overexpression of the SIR2 gene is sufficient to extend lifespan in yeast. SIR stands for silent information regulator, and we have an interesting discussion about how Matt’s research and 1999 discovery have elevated SIR2 to the forefront of aging research. Also, some of Matt’s most recent and fascinating investigations have been into rapamycin, the only known pharmacological agent to extend lifespan.  His research has shed new light on the role rapamycin plays in delaying age-related dysfunction in rodents, dogs, and humans. We also have a fun discussion with Matt about his research showing that rapamycin may have the potential to reduce the mortality of companion dogs. The paper that came out of this research landed Matt on the front page of the New York Times and received prominent play in the national and overseas media. Other topics we cover include: Matt’s attempts to uncover the molecular mechanism behind lifespan extension via calorie restriction. His research into mTOR, which is a protein in every cell, and how inhibiting mTOR has been shown to extend the lifespan of insects, rodents, and animals. Matt’s 2006 study that showed fasting extends lifespan in worms more than caloric restriction. And an article Matt published last year that summarized several of the most popular anti-aging diets, comparing them with classical caloric restriction. In addition to his work in his Kaeberlein Lab, Matt is the co-director of the Nathan Shock Center of Excellence in the Basic Biology of Aging and the founding director of the Healthy Aging and Longevity Research Institute at the University of Washington. He also is the founder and co-director of the Dog Aging Project. Show notes: [00:02:53] Dawn asks Matt and his youth and where he grew up. [00:03:06] Ken asks if it is true that Matt spent a good deal of his youth “up to no good.” [00:04:20] Dawn mentions that while Matt got decent grades in school, it wasn’t until he went to college that he became studious. Dawn asks Matt if it true that he had originally decided to skip college. [00:05:42] Dawn asks how Matt ended up in Bellingham at Western Washington. [00:06:41] Dawn asks how in the world, despite not liking high school and working a morning shift at UPS for two years after graduating, Matt decided to head off for college and major in biochemistry of all things. [00:08:01] Ken asks what led Matt to travel across the country to Boston and MIT’s biology program. [00:09:57] Ken asks why Matt decided to focus his research on the biology of aging. [00:11:57] Matt talks about what he did following his Ph.D. [00:13:15] Dawn asks Matt what kind of research he did at the University of Washington Department of Genome Sciences for his post-doc, and how this research related to aging. [00:15:10] Ken mentions that it was during Matt’s undergrad that he decided to focus on the question, “To what extent are the mechanisms of aging evolutionarily conserved?” Ken asks Matt what caused him to arrive at that for his central focus. [00:19:36] Dawn mentions that the discovery by Matt, and Mitch McVey, that overexpression of SIR2 (Silent Information Regulator) is sufficient to extend life span in yeast is credited with promoting SIR2 to the forefront of aging research. Dawn goes on to mention that SIR genes are determinants of life span in yeast mother cells. Dawn asks Matt to give a quick primer on the SIR genes and their functions. [00:20:55] Ken follows up asking about Matt’s 1999 paper that appeared in the journal Genes and Development. Matt talks about this paper and how he demonstrated that increasing the dosage of SIR2 extended lifespan. [00:23:42] Dawn mentions that after Matt arrived at the University of Washington, he began looking at yeast and C. elegans, to see if there were key aspects of aging that could be related to humans. This research led to Matt and his colleagues publishing a paper in 2008 demonstrating quantitative evidence for conserved longevity pathways between different eukaryotic species. Dawn asks Matt to talk about how today most people agree that there are key aspects of aging shared across all animals, even down to yeast. [00:27:27] Dawn asks about Matt’s lab and the work he does at the University of Washington as well as the work he does as the director of the Healthy Aging and Longevity Research Institute as well as the work he does as director of the Nathan Shock Center of Excellence in the Basic Biology of Aging Training Program. [00:30:06] Dawn asks about some papers Matt published in 2004 and 2005, which attempted to uncover the molecular mechanism behind lifespan extension via calorie restriction, which has been seen across a wide variety of animals. Dawn mentions that one of Matt’s 2004 papers disproved the model that caloric restriction acts solely through SIR2 to mediate lifespan extension and asks him to talk about that discovery. [00:36:31] Ken follows up asking Matt to talk more about his TOR and mTOR related work. [00:39:57] Dawn mentions that Matt’s lab followed up these aforementioned papers with a study that showed fasting extends lifespan in worms more than caloric restriction, in which the worms were fasted for their entire adulthood. Matt talks about the findings and implications of this study. [00:43:41] Ken asks about Matt’s research into rapamycin and the role it plays in increasing the lifespan of rodents and delays age-related dysfunction in both rodents and humans. Ken asks specifically about Matt’s 2016 study, the findings of which suggest that short-term rapamycin treatment late in life can not only delay aging but also influence cancer prevalence and modulate the microbiome. [00:47:43] Dawn mentions Matt’s research that garnered the attention of the NY Times, where he began treating dogs with rapamycin and asks what prompted Matt’s interest in studying dogs and aging. [00:51:06] Ken mentions Matt’s article in Nature published earlier this year, where he explained that the primary goal of the Dog Aging Project is to generate and facilitate discoveries on the fundamental biology of aging. He also argued that the impact of the Dog-Aging Project will go far beyond this goal and Ken asks Matt to explain what he meant by that. [00:53:46] Dawn asks about Matt’s recent paper in eLife that looked at whether rapamycin could rejuvenate oral health in mice, and goes on to explain that periodontal disease is prevalent in elderly human populations and currently has no therapy that can effectively reverse it. Matt talks about this study and the promising results from it. [00:56:21] Dawn asks about Matt’s recent review summary that appeared in the journal Science last year that looked at several of the most popular anti-aging diets, comparing them with classical caloric restriction. Matt gives an overview of the interventions evaluated and what insights were gained. [01:01:38] Ken mentions that IHMC has done some studies on ketone esters and asks about Matt’s opinion on findings that suggest that ketone esters by themselves could have antiaging properties. [01:04:59] Ken asks about Matt’s opinion that a case can be made that mTOR complex 1 is a particularly relevant and robust molecular transducer of diet-induced antiaging signals. [01:08:41] Ken asks if mTOR complex 1 is the complex that is involved in muscle protein synthesis. [01:11:31] Ken brings up the point that discussions of mTOR inhibition via rapamycin is often coupled with the idea of inhibition of protein synthesis which leads to confusion regarding the difference between not having enough protein in the diet and inhibiting protein synthesis. Matt brings up the point that transient inhibition of mTOR will have different effects than continued chronic inhibition of mTOR, making dosing and timing important variables in this question. [01:13:08] Ken and Matt discuss the self-experimentation that many people have begun to do with rapamycin. They also discuss the possible interaction of rapamycin and resistance exercise in humans. [01:14:58] Ken asks, based on all the current findings regarding rapamycin, whether Matt thinks we are at the point where people should start seriously considering rapamycin or if more research needs to be done first. [01:17:55] Ken asks if Matt has perceived a benefit from his own personal use of rapamycin. [01:20:06] Dawn asks Matt, as someone who lives by the motto “live long or die trying,” what are the strategies that he uses in terms of diet, supplements, and exercise. [01:23:46] Dawn asks Matt how his dog is doing to close the interview. Links: Matt Kaeberlein bio Kaeberlein lab Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio  

Today’s guest is Dr. Mark Lewis, executive director of NDIA’s Emerging Technologies Institute (NDIA ETI), a nonpartisan think tank focused on technologies that are critical to the future of national defense. ETI provides research and analyses to inform the development and integration of emerging technologies into the defense industrial base.   We will discuss the Emerging Technologies Institute’s Vital Signs report, which is an evaluation of the readiness and health of the defense industrial base. Prior to his role at the Emerging Technologies Institute, Mark was the Director of Defense Research & Engineering in the Department of Defense, overseeing technology modernization for all military services and DoD Agencies, as well as the acting Deputy Under Secretary of Defense for Research & Engineering.  In this role he was the Pentagon’s senior-most scientist, providing management oversight and leadership for DARPA, the Missile Defense Agency, the Defense Innovation Unit, the Space Development Agency, Federally Funded Research and Development Centers, and the DoD’s basic and applied research portfolio. At the Department of Defense, Mark worked closely with Mike Griffin, who appeared on episodes 23 and 134 of STEM-Talk. In today’s interview with Mark, we will again discuss hypersonics and other emerging technologies and modernization priorities that are critical to our national defense. Mark is also the former longest-serving and is perhaps best known for his work in hypersonics. In addition to these important defense-related roles, Mark is also a professor emeritus at the University of Maryland. He spent 25 years as a faculty member at Maryland, conducting basic and applied research in hypersonic aerodynamics, advanced propulsion, and space-vehicle design. Show notes: [00:03:27] Dawn opens the interview asking where Mark grew up and what he was like as a kid. [00:04:29] When Dawn asks Mark when he first became interested in science, Mark tells a funny story form his time as president of the American Institute of Aeronautics and Astronautics? [00:06:21] Ken asks Mark how he ended up at MIT after high school. [00:07:46] Mark talks about taking a job as an assistant professor of aerospace engineering at the University of Maryland after earning his Ph.D. in aeronautics and astronautics at MIT. [00:09:34] Dawn mentions that from 2002 to 2004, Mark was the director of the Space Vehicle Technology Institute. She asks Mark to give an overview of the Institute and the kind of work that goes on there. [00:12:45] Ken mentions that in 2004, Mark became Chief Scientist of the U.S. Air Force, going on to become the longest-serving Chief Scientist in Air Force history. Ken asks Mark to explain the role of the chief scientist, and what he focused on during his time in the position. [00:17:37] Dawn explains that in 2012, Mark became the director of the Science and Technology Policy Institute, which worked with the executive office of the President and other Executive Branch agencies. Mark talks about the kind of work the Science and Technology Policy Institute does. [00:20:23] Dawn mentions that during Mark’s 25 years as a faculty member at the University of Maryland, he conducted basic and applied research in a variety of fields, such as hypersonic aerodynamics, space vehicle design, and advanced propulsion.  She point out that Mark, however, is best known for his work in hypersonics. She asks Mark what led him to focus on hypersonics. [00:22:46] Ken asks Mark to explain why he decided to work under Mike Griffin (episodes 23 and 134) in the Pentagon as the Director of Defense Research and Engineering, and what that experience was like. [00:28:19] Dawn mentions that during Mike Griffin’s time as Under Secretary of Defense for Research and Engineering, he made hypersonics the department’s number one priority. Dawn asks Mark to explain the importance of hypersonics in terms of our national defense. [00:33:38] Ken asks Mark when he thinks an air breathing hypersonic tactical round might be available on a production basis. [00:35:40] Ken mentions that Russia recently test-launched the RS-28 Sarmat, a liquid-fueled MIRV-equipped super-heavy intercontinental ballistic missile, sometimes referred to in the west as the “Satan II.” Mark gives his take on the RS-28. [00:39:44] Dawn explains that in 2008, when Mark was concluding his time as Chief Scientist of the Air Force, he launched a study that became known as the Day Without Space Study. This study concluded that we would have a very hard time fighting a war without our relatively vulnerable space assets. Dawn asks Mark to talk about the importance of space in our national defense. [00:43:03] Ken asks Mark about directed energy technology, and its importance in terms of our national defense and weapons capabilities. [00:45:02] Mark discusses his new role as the executive director of the National Defense Industrial Association’s Emerging Technologies Institute, which is a nonpartisan institute focused on technologies that are critical to the future of our national defense. [00:47:28] Dawn asks about the Institute’s ongoing initiative called the Vital Signs Project, which is a report that measures the well-being of the nation’s defense industrial base. [00:48:41] Ken mentions that the 2022 Vital Signs report came out earlier this year with the defense sector receiving an overall poor grade of 69, which is three points below last year’s grade. Ken asks what effect these reports are having. [00:49:50] Dawn explains that in 2022, the authors of the Vital Signs report assigned a failing grade in five areas, with one of the most troubling declines being in supply-chain performance. Dawn goes on to say that the report noted that the decline reflected the turbulence the economy is facing, some of it caused by the COVID-19 pandemic. She also points out that next year’s report is expected to report even greater supply chain issues and she asks Mark to explain why this is such a major problem for the Pentagon. [00:51:57] Ken mentions that another significant drop came in productive capacity and surge readiness. He asks Mark to define what is meant by the term “surge readiness.” [00:54:28] Dawn asks Mark for his take on the fact that U.S. government funding for research and development fell by 12 percent between 2011 and 2016, while in the same time frame China increased its R&D investments by 56 percent. [00:58:54] Ken asks if we are doing a good job of not only researching and developing technologies for our national defense, but also pushing these developments into practical production. [01:02:54] Ken circles back to hypersonics, explaining that the U.S. used to be the world leader in this technology, partly because of our past test-fail approach to innovation. Ken explains that there is a real resistance to that approach to research today in Congress and asks Mark if he believes we need a return to this old mindset for innovation if we are going to catch up with the Chinese and Russians. [01:12:33] Dawn asks what Mark likes to do in his spare time. [01:13:44] Dawn closes the interview and thanks Mark for his time. Links: Mark Lewis bio Learn more about IHMC STEM-Talk homepage  Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Today we return with the second half of our two-part interview with Dr. Greg Potter, a British researcher who specializes in circadian biology, sleep, diet, and metabolism. In this second part of our interview, host Ken Ford and Greg continue their conversation about circadian biology and cover topics ranging from insomnia, sleep apnea, time-restricted eating, exercise, nutrition, and supplementation. In part one of our interview, episode 136, Ken talked to Greg about how he became interested in circadian biology and the importance of synchronizing our lifestyles to be in tune with our circadian rhythms. Greg also explains why he decided to specialize in sleep and what his research has taught him about the role and importance of melatonin, a hormone that helps control the body’s sleep cycle. Dawn Kernagis was traveling during our talk with Greg and couldn’t join Ken to co-host the interview.  Greg gained attention in the U.S. and Europe for his research into the importance of biological rhythms and sleep and how they affect people’s lives. His work has been featured in the BBC World Service, the Washington Post, Reuters and other scientific journals and news outlets. In addition to being a science writer and sleep consultant, Greg also is an entrepreneur who co-founded Resilient Nutrition in 2020, a company that leverages science to produce foods and supplements geared toward helping people feel and perform better. Greg earned undergraduate and master’s degrees in exercise science from Loughborough University in England a Ph.D. from the University of Leeds. Show notes: [00:03:12] Ken opens part two of our interview with Greg by asking him about continuous positive airway pressure machines, known as CPAPs, that are used for sleep apnea and related disorders, and how these devices relate to circadian rhythms and quality of sleep. [00:05:47] Ken brings up chronotypes, the concept that some people are better suited to an earlier or later sleep schedule. Ken goes on to say that during our interview with Satchin Panda, he argued that chronotypes are largely a myth. Ken asks Greg how much he thinks chronotypes are the product of environment as opposed to evolutionary biology and genetics. [00:10:27] Ken asks what an example would be of an advanced chronotype. [00:11:54] Ken asks Greg about chrononutrition, which is the relationship between a person’s nutrition and their body clock. [00:20:46] Ken mentions that muscle protein synthesis comes up as a problem for people getting older who begin a fasting diet which is generally good for their health but prevents them from maintaining or gaining substantial muscle mass, as their protein demands are higher than they were in youth. Ken asks Greg his thoughts on a pulsatile approach to fasting and protein intake for this cohort. [00:23:39] Ken asks Greg about chronopharmacology, what it is and how it might tie into nutrition. [00:25:21] Ken asks Greg to explain his stance that we should re-engineer our lifestyles to better mimic certain aspects of our distant ancestors to protect ourselves from chronic diseases and revive the kinds of energy we had as children. Greg explains what aspects of our ancient ancestors we ought to emulate. [00:29:07] Ken mentions a paper Greg published on sleep and bodyweight, and asks Greg to expound on the relationship between sleep and weight regulation. [00:33:54] Ken asks if Greg thinks it is true that there is now an “epidemic” of sleep loss. [00:36:57] Greg gives a list of advice for people to optimize their sleep. [00:40:57] Ken mentions that many people enjoy a little wine or other drink before bed because they feel as if it helps them fall asleep. Ken asks Greg to talk about how this can damage a person’s sleep. [00:43:52] Ken asks when people should go to bed, and how much sleep is needed for a person on average, and how much variation there is in the quantity of sleep needed between people. [00:49:12] Ken asks Greg what people should consider when selecting sleep supplements. [00:52:39] Ken mentions that during the COVID-19 pandemic, Greg ventured into the world of entrepreneurship and launched a new company, Resilient Nutrition. Ken goes on to say that Greg has recently launched a new product called Switch On, which Greg has called the first supplement specifically formulated to mitigate some of the negative effects of lost sleep. Ken asks Greg to talk more about this. [00:57:45] Greg talks about the importance of unwinding at the end of the day and some strategies to aid in that, as well as the importance of having a healthy attitude towards sleep. [01:01:14] Ken ends the interview asking Greg if sexual activity prior to sleep influences the quality as well as the duration of sleep.    

British researcher Greg Potter discusses circadian biology and the importance of sleep. He shares his academic background and interest in circadian biology, childhood interests, journey into sports science, and development of interest in circadian rhythms and sleep. He also explores the roles of peripheral clocks in glucose regulation and cardiovascular function, the impact of the social clock on humans, and the implications of shift work on health and performance.