Episode 94: John Newman discusses how the ketogenic diet and fasting regulate the genes and pathways that control aging
// Aug 20, 2019
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.