Episode 94: John Newman discusses how the ketogenic diet and fasting regulate the genes and pathways that control aging

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...