In this episode, Rhonda describes NAD+ (perhaps one of the most important molecules in the human body), why it is so important for aging, and why it declines with age. She discusses some of the popular NAD+ boosters like nicotinamide riboside and nicotinamide mononucleotide, explains what the animal and human data say, discusses some of the concerns associated with using these boosters, and provides some concluding thoughts. Learn more about NAD+ Learn more about nicotinamide riboside Learn more about nicotinamide mononucleotide Learn more about sirtuins Get earlier access with the premium members early access podcast feed, monthly Q&A sessions, an exclusive bi-weekly science digest email, and more! Click here to get started.
David A. Sinclair, PhD, is a professor in the Department of Genetics at Harvard Medical School and co-director of the Paul F. Glenn Center for the Biological Mechanisms of Aging. He is the co-founder of the journal Aging, where he serves as co-chief editor. Dr. Sinclair's work focuses on understanding the mechanisms that drive human aging and identifying ways to slow or reverse aging's effects. In particular, he has examined the role of sirtuins in disease and aging, with special emphasis on how sirtuin activity is modulated by compounds produced by the body as well as those consumed in the diet, such as resveratrol. His work has implications for human metabolism, mitochondrial and neurological health, and cancer. In this episode, we discuss... 00:17:59 - How caloric restriction, fasting, and exercise increase levels of a molecule called NAD+ and how this activates sirtuins, a family of genes involved in longevity. 00:21:47 - How NAD+ levels and sirtuin activities decrease with age, and how animal studies suggest that raising cellular NAD+ levels can trick the body into thinking it is younger. 00:23:03 - How resveratrol enhances the binding of sirtuins to NAD+ thus making sirtuins more easily activated for a longer period. 00:27:36 - We also discuss Steve Horvath's epigenetic aging clock, which measures DNA methylation groups, and how they may play a role in widespread gene regulation, including sirtuin genes, and how NAD+ may participate in resetting the clock. 00:31:54 - How the signal that resets the epigenetic clock in mice involves the Yamanaka factors -- a group of four transcription factors that can reprogram an adult cell to become a pluripotent stem cell that can form any cell type. 00:46:48 - How resveratrol is a xenohormetic compound and is produced when grape plants are stressed either in response to fungus or lack of water. 00:55:35 - How a phase 2 clinical trial involving people with Alzheimer's disease showed resveratrol improved cognitive function, improved cerebrospinal fluid amyloid beta levels, lowered markers of activated microglia, and more. 00:58:03 - How both nicotinamide riboside and nicotinamide mononucleotide have been shown to improve cognitive function and brain pathology in mice that have been engineered to get a disease similar to Alzheimer's disease. 01:06:19 - How older mice that were given nicotinamide mononucleotide experienced delayed aging in the liver, muscle, immune cells, eyes, and bones, but those that took a lower dose had improved mitochondrial function and enhanced physical performance. 01:01:22 - How there may be challenges in translating animal studies on nicotinamide riboside and nicotinamide mononucleotide to humans particularly due to the need to determine the dose required to promote health benefits. And so much more! Click here to get this episode's show notes and transcript Watch this episode's highlights on the FMF Clips channel Get early access with the premium members early access podcast feed, monthly Q&A sessions, an exclusive bi-weekly science digest email, and more! Click here to get started. Submit your raw genetic data to get the latest version of the genetic report at foundmyfitness.com/genetics.
This podcast is the audio from a presentation Dr. Rhonda Patrick gave on how the sauna may be an exercise mimetic for heat health and healthspan. Sauna use has emerged as a means to increase lifespan and improve overall health, based on compelling data from observational, interventional, and mechanistic studies. Listen in to find out more. Click here to get the episode show notes and video. Watch the episode with cardiologist and sauna scientist Dr. Jari Laukkanen. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how to support the podcast.
In this short episode, Dr. Patrick discusses some of the compelling science including observational studies, randomized controlled trials, and human mechanistic studies that suggests exercise is a powerful tool for preventing or managing the symptoms of depression and mental illness. Moreover, she talks about the specific types of exercise and exercise parameters that evidence suggests might be the most helpful for depression. This podcast started its life as a video, so make sure to check out the full video or the references and episode notes on the episode page. Click here to get this episode's show notes and video. Click here to visit the in-depth depression topic page. See the full interview with Dr. Charles Raison. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how to support the podcast and access the premium members benefits.
Elissa Epel, PhD, is a Professor in the Department of Psychiatry at the University of California, San Francisco where she serves as the director of the Aging, Metabolism, and Emotions Center. Her research centers on the mechanisms of healthy aging and the associations between stress, telomere length, addiction, eating, and metabolic health. In this episode, we dive deep into the world of telomeres, the length of which is one of the useful biomarkers scientists have for getting a sense of the differences between how individuals or groups of individuals age. Telomere shortening is both a cause and a symptom of aging and plays key roles in not only how long we live, but in how well. Lifestyle factors such as poor nutrition and smoking can accelerate telomere shortening by generating oxidative stress and inflammation. Click here to get this episode's show notes and transcript. Watch this episode's highlights on the FMF Clips channel. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how to support the podcast for as little or as much as you like. Submit your raw genetic data. You can find the Telomere report at foundmyfitness.com/genetics.
Matthew Walker, Ph.D., is a professor of neuroscience and psychology at the University of California, Berkeley, and serves as the Director of the Center for Human Sleep Science. Formerly, Dr. Walker served as a professor of psychiatry at the Harvard Medical School. Walker's research examines the impact of sleep on human health and disease. One area of interest focuses on identifying "vulnerability windows" during a person's life that make them more susceptible to amyloid-beta deposition from loss of slow wave sleep and, subsequently, Alzheimer's disease later in life. Dr. Walker earned his undergraduate degree in neuroscience from the University of Nottingham, UK, and his Ph.D. in neurophysiology from the Medical Research Council, London, UK. He is the author of the New York Times best-selling book Why We Sleep: Unlocking the Power of Sleep and Dreams. Click here to get this episode's show notes and transcript. Watch nearly twenty-seven episode highlights on the new FMF Clips channel. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how to support the podcast for as little or as much as you like. Submit your raw genetic data. You can find the APOE report and the Circadian Report at foundmyfitness.com/genetics.
This episode features a Q&A session with Dr. Rhonda Patrick. The questions were sourced from social media followers of both FoundMyFitness and also Zero Fasting Tracker, a convenient mobile app used widely in the fasting community for logging. In this 45-minute podcast, Dr. Patrick answers some of the most popular questions related to fasting, including: What effects coffee, supplements, and amino acids have on fasting Whether one method of fasting is more beneficial than others What effect the consumption of exogenous ketones have on fasting Whether it is good to exercise while fasting The ideal way to break a fast How fasting affects muscle mass How fasting plays a role in the growth-longevity tradeoff ... and more! Watch the video of the conversion or get the timeline here. Learn how you can support the FoundMyFitness podcast for as little or as much as you like by clicking here.
Dale E. Bredesen, M.D., is a professor of neurology at the Easton Laboratories for Neurodegenerative Disease Research at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA). Dr. Bredesen's laboratory focuses on identifying and understanding basic mechanisms underlying the neurodegenerative process and the translation of this knowledge into effective treatments for Alzheimer's disease and other neurodegenerative conditions. He has collaborated on the publication of more than 220 academic research papers. His work has culminated in the development of a protocol called ReCODE – reversal of cognitive decline – currently used by over 3,000 patients with the goal of not just preventing, but reversing Alzheimer's disease and mild cognitive impairment. Click here to get the episode's show notes and transcript. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how you can support the podcast for as little or as much as you like. Submit your raw genetic data.You can find the APOE report at foundmyfitness.com/genetics.
This podcast is a spectacular round two podcast with Dr. Valter Longo. Dr. Longo is the current director of the longevity institute at the University of Southern California and also director of the Oncology and Longevity Program at the Institute of Molecular Oncology Foundation in Milan, Italy. Dr. Longo’s research focuses understanding the biological mechanisms that regulate the aging process, the role of fasting and diet in longevity and healthspan in humans as well as metabolic fasting therapies for the treatment of human diseases. In this episode, we discuss... What two seminal studies on chronic caloric restriction in primates from the 80s teach us about caloric restriction as a preventer of age-related disease, and how the effects of caloric restriction may actually be stronger when the diet that is being restricted is an unhealthy one – similar, in some ways, to the typical western diet. How certain macronutrients influence the insulin/IGF-1/growth hormone axis interact to modulate aging in many cell types. How mice and humans who have growth hormone receptor deficiencies have low circulating IGF-1 – as little as 10% of normal levels – and have reduced risk of diseases like cancer, diabetes, and age-related cognitive decline, hinting at what future research might reveal about the beneficial effects of prolonged fasting and fasting-mimicking diets through the downstream effects of periodic deprival of growth-related factors. How the growth hormone / IGF-1 axis got a big boost early on in scientific interest when it was revealed that mice that have either deficiency in growth hormone itself or the growth hormone receptor live up to 40% longer and how this is accomplished through what is essentially a delaying of the decrepitudes of old age. The origins of what Dr. Longo calls the fasting-mimicking diet – a 5-day diet focused on recapitulating some of the benefits of prolonged fasting, like dramatic changes in metabolic biomarkers, but without some of the drawbacks like reduced compliance and other risks that can come with multiple days of grueling strict water fasting in large, heterogeneous populations. How periodic prolonged fasting or the fasting-mimicking diet may be able to render cancer cells more vulnerable while conferring stress resistance to healthy cells, a quality known as differential stress resistance. This can happen because of the way fasting interferes with what is known as oncogenic signaling. The mixed results associated with the use of the ketogenic diet in treatment of cancer and how some cancers seem to be hurt by the metabolic switch of utilizing ketone bodies, which creates oxidative stress from the use of mitochondria, while other cancers seem to be able to use ketones effectively as an energy source, potentially accelerating their growth. Some of the early but promising pre-trial clinical anecdata suggesting potential complementary roles for the ketogenic diet and the fasting-mimicking diet (FMD) used in conjunction with conventional treatments like chemotherapy or radiotherapy for certain cancers like gliomas. In the context of aging, how the fasting mimicking diet has been shown to “reset” metabolism, driving down biomarkers associated with poor metabolic health, inflammation, and cardiovascular health. How fasting, through the shrinking and then re-expansion of whole systems like the liver, kidneys, heart, and immune cells may represent a type of whole-system renewal that originated as a three-billion-year-old self-repair mode that was only activated during periods of famine or inconsistent food availability, but might now be dormant in people living in a modern world of regular food intake. How Dr. Longo’s group has shown that, in animal models of multiple sclerosis and pharmacologically-induced type 1 diabetes, several cycles of the fasting-mimicking diet is able to reverse disease and restore healthful function. This mechanism also may generalize to erasing other diseases of autoimmunity through the destruction of autoimmune immune cells that are essentially reset through fresh differentiation from progenitors untainted by autoimmunity. A very exciting area of continued inquiry! How shorter fasts may fail to approach some of the effects of periodic fasting and the fasting-mimicking diet by failing to achieve adequate glycogen depletion and ketogenesis. Dr. Longo’s “top picks” for assessing biological age – markers a person can ask their doctor to measure to gauge how well they’re aging. A sneak peek at what’s covered in Dr. Longo’s new book, The Longevity Diet. … and so much more. Go to the timeline on the episode page to see a full breakdown. Click here to visit the episode page and show notes now. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how you can support the podcast for as little or as much as you like.
Charles Raison, M.D. is a professor at the School of Human Ecology at the University of Wisconsin-Madison and Founding Director of the Center for Compassion Studies in the College of Social and Behavioral Sciences at the University of Arizona. Dr. Raison’s research focuses on inflammation and the development of depression in response to illness and stress. He also examines the physical and behavioral effects of compassion training on the brain, inflammatory processes, and behavior as well as the effect of heat stress as a potentially therapeutic intervention major depressive disorder. In this nearly 2-hour episode, we discuss the extremely dynamic interaction that the immune system has with mood, behavior, and the brain, as well as the potential that whole-body hyperthermia, a research technique mostly indistinguishable from sauna use, may have for the treatment of clinical depression. Additionally, we also talk about…. How depression as a disease may be subdivided based on whether or not there is involvement of chronic inflammation and how this could influence how it should be treated. The changes in functional brain connectivity that are associated with the high inflammation subtype of depression. The physiological similarities a sauna, hot bath, steam shower, and hot yoga have with whole-body hyperthermia from the standpoint of potentially therapeutically boosting body temperature. Preliminary evidence that increased expression of a certain heat shock protein in the brain may influence behavior by protecting against stress-induced depression. … and so much more. Go to the timeline on the episode page to see a full breakdown. Click here to visit the episode page and show notes now. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how you can support the podcast for as little or as much as you like.
Eric M. Verdin, M.D. is the fifth president and chief executive officer of the Buck Institute for Research on Aging and is a professor of Medicine at UCSF. Dr. Verdin's laboratory focuses on the role of epigenetic regulators in the aging process, the role of metabolism and diet in aging and on the chronic diseases of aging, including Alzheimer’s, proteins that play a central role in linking caloric restriction to increased healthspan, and more recently a topic near and dear to many of you, ketogenesis. He's held faculty positions at the University of Brussels, the NIH and the Picower Institute for Medical Research. In this episode, we discuss... The effects of a low protein, cyclic ketogenic diet beginning in midlife (12 months of age) in male mice. The result? Increased healthspan and improved memory. Dr. Verdin explains how the cyclic ketogenic diet decreased insulin, IGF-1, and mTOR signaling and decreased fatty acid synthesis, and increased PPAR-alpha (which promotes beta-oxidation and mitochondrial biogenesis in muscle). How this diet is somewhat qualitatively similar to fasting. Some of the possible reasons why the cyclic ketogenic diet created such a striking improvement in memory even when compared to younger mice. How beta-hydroxybutyrate, which is the major circulating ketone body during fasting and nutritional ketosis, may, in addition to being an energy source, regulate inflammation and gene expression by acting as a signaling molecule by inhibiting what are known as class 1 histone deacetylases (HDACs). How this inhibition of class 1 HDACs leads to the increased expression of notorious longevity gene Foxo3, which may help explain why mice given an exogenous beta-hydroxybutyrate ester had lower markers of inflammation and oxidative damage, which are physiological contributors to the aging process. The role of the nicotinamide adenine dinucleotide (NAD+) in the aging process and how replacing declining levels (or preventing them from declining in the first place) may prove to be an important anti-aging strategy. Some of the reasons why NAD+ might be declining with age, its role in DNA damage repair via an enzyme known as PARP, and what the literature says about the NAD+ precursor nicotinamide riboside. How a special class of enzymes called sirtuins, also known to be activated by caloric restriction and caloric restriction mimetic resveratrol, is tightly correlated with the level of NAD+ and how this "energetic currency" rises in response to fasting. The role of the sirtuin enzymes in regulating mitochondrial function, neuronal functions, stem cell rejuvenation and why they may be important in delaying the aging process. Grab the full show notes, timeline & glossary from the episode page now. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how you can support the podcast for as little or as much as you like.
This is a nearly 2-hour round 2 episode with none other than Dr. Satchin Panda of the Salk Institute! At nearly two hours of dialog, this episode touches on a lot of material but has a special focus on practical implementation of time-restricted eating. Put another way, I kept a list of a lot of questions that seem to keep coming up and present them directly to Satchin. We talk about dealing with shift work, black coffee when fasting, and some of the distinctions between Satchin's approach to time-restricted eating which is influenced by his deep background in circadian biology and more conventional protocols like 16:8 that many people are familiar with. In addition to these important and very practical how-to tidbits, we dive into lots of interesting new territory as well, including... How human anecdote and animal evidence suggests time-restricted feeding may be especially useful for gut-related issues, including inflammatory bowel disease and acid reflux. The fascinating way Dr. Panda is using human anecdote from his trial to ask new scientific questions he wouldn't think to ask and then going back to animal data to figure it out and how this unique approach forms a sort of closed loop pattern: animal → human feedback → back to animal for mechanism. How labs doing caloric restriction research may have actually been reaping the benefits of time-restricted without realizing it as an incidental to their experimental design. The revelation that 70% of FDA drugs are subject to circadian effects and are either less effective or more effective at certain times of the day. The effect melatonin has on the pancreatic production of insulin and the insight this lends to why we should probably stop eating 3-4 hours before we go to bed. The bizarre way circadian rhythms affects everything from susceptibility to UV damage to recovery from surgery to cancer risk. Sign-up for Dr. Panda's mobile app study on time-restricted eating. Grab the full show notes, timeline & glossary from the episode page now. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how you can support the podcast for as little or as much as you like.
Dr. Guido Kroemer is a professor at the University of Paris Descartes and an expert in immunology, cancer biology, aging, and autophagy. He is one of the most highly cited authors in the field of cell biology and was the most highly cited cell biologist for the period between 2007 and 2013. Especially notable among his contributions: he was the first to discover that the permeabilization of mitochondrial membranes is a concrete step towards apoptotic cell death. This episode is decidedly focused on autophagy, an important cellular program that is inducible by dietary fasting and has broad implications for aging and cancer. Autophagy discussion includes: How the 3 main signals that activate autophagy all involve nutrient sensing (00:09:09). The role of different types of fasting and nutrient deprivation in autophagy (00:20:55). How different types of exercise can induce autophagy (00:24:35). How a specific type of autophagy called mitophagy keeps mitochondria healthy (00:36:29). How autophagy has been shown to slow cellular aging (00:33:07). How autophagy prevents neurodegenerative diseases by clearing away protein aggregates (00:39:38). The role of autophagy in cancer as a possible double-edged sword (00:48:29). How certain compounds known as caloric restriction mimetics (or fasting mimetics) including resveratrol, spermidine, hydroxycitrate can induce autophagy by tricking the cell through the modulation of one or more of the 3 main autophagy signaling pathways (00:54:52). Visit Dr. Guido Kroemer's website. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how you can support the podcast for as little or as much as you like. Watch the full video on YouTube.
This podcast features Jari Laukkanen, M.D., Ph.D., a cardiologist and scientist at the Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio. Dr. Laukkanen has been conducting long-term trials looking at the health effects of sauna use in a population of over 2,000 middle-aged men in Finland. The results? Massive reductions in mortality and memory disease in a dose-response fashion at 20-year follow-up. In this almost 25-minute episode, we talk about... 00:00:37 - The association between sauna use and fatal cardiovascular outcomes. 00:00:37 - The inverse association between cardiovascular-related deaths and all-cause deaths. 00:02:00 - How men that used the sauna 2-3 times per week had a 27% lower cardiovascular-related mortality than men that used the sauna 1 time per week. 00:02:15 - How men that used the sauna 4-7 times per week had a 50% lower cardiovascular-related mortality than men that used the sauna one time per week. 00:02:50 - The confounding factors Dr. Laukkanen and his colleagues had to adjust for, such as physical exercise, cholesterol, obesity, smoking, alcohol consumption, socioeconomic status. 00:03:26 - The various types of cardiac-related deaths their reductions were shown in, including coronary artery disease, sudden cardiac death and more. 00:05:00 - How one of the major mechanisms by which sauna use improves heart health is by reducing blood pressure and incident hypertension. 00:05:40 - The mechanisms by which the sauna lowers blood pressure, which can occur via balancing of the autonomic nervous system, improvements in blood vessel function, decreases in arterial stiffness and compliance of arteries. 00:06:17 - The increases in heart rate seen with sauna use that make it similar to moderate aerobic exercise in some ways (up to 150 beats/min!). 00:06:56 - How time spent in the sauna was one of the more important factors for risk reduction with at least 20 minutes per session in a 174 F (79C) 4-7 times per week being a "sweet spot." 00:09:29 - The inverse, dose-response relationship between sauna use and all-cause mortality: 24% for 2-3 times per week, 40% for 4-7 times. 00:10:00 - His newest study that now shows a reduction in risk in a similar dose-response fashion for dementia and Alzheimer’s disease by around 65% for the most frequent sauna users. 00:10:18 - The way sauna use increases heat shock proteins which repair damaged proteins and prevent protein aggregates and how this could end up being at least one potential molecular mechanism at play. 00:13:03 - How sauna use increases growth hormone by 200-330%. 00:14:10 - The patterns of sauna use and especially whether to sauna before or after you weight train. 00:15:55 - The effect of sauna on mood which may be from improvements in cardiorespiratory fitness and possibly endorphins as well. 00:18:39 - How sauna improves heart rate variability. 00:20:04 - Cold-water immersion after sauna and a few cautionary words for extreme contrast therapy in people with a pre-existing heart condition that is currently unstable. Send Dr. Jari Laukkanen a tweet on Twitter. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how you can support the podcast for as little or as much as you like.
Dr. Judith Campisi is a professor of biogerentology at the Buck Institute for Research on Aging and a co-editor in chief of the Aging Journal. As an expert on cellular senescence, the discussion involves a lot of talk about aging and cancer, where senescence plays a very important fundamental role. What are some of the strategies we might use in the future to prevent senescent cells? What causes them in the first place? In this 1-hour long conversation, we discuss a great number of very interesting things including: Why diseases of aging, despite occurring in vary diverse tissue types, all begin to crop up simultaneously after 50 or 60 years of life. What the fundamental molecular processes of aging are and what some of the on-going research and general thoughts are surrounding these processes. What senescence is and the evolutionary biology explanation for why we have the mechanism of cellular senescence in the first place. The infiltration of immune cells into our tissues that occurs as a function of aging and the role of damaged or senescent cells in attracting these immune cells. The changes in gut permeability that happens with age and how that may increase our susceptibility to chronic, low-level inflammation. The role of senescent cells in cancer metastasis and progression. The clearance of senescent cells as a valid life extension strategy. How mitochondrial dysfunction, even in the absence of DNA damage, can cause cells to undergo senescence. The interesting observation that senescence from damage versus energy crisis (failed mitochondria) demonstrates a different and unique phenotype of cellular senescence. The effects prolonged fasting may have on the clearance of senescent cells. How periodic prolonged fasts might mimic some of the effects associated with an mTOR dampening drug like rapamycin. How the secretions of senescent cells can affect the regenerative capacity of stem cells. The practicality of a consumer available clinical assays for DNA damage and the challenge of assessing tissue-specific senescence without the use of invasive biopsy. The effect of so-called fasting mimetic compounds (e.g. hydroxycitrate, resveratrol & spermidine) on senescent cells. And believe it or not much more! Studies mentioned: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Learn more about Dr. Judy Campisi. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how you can support the podcast for as little or as much as you like.
Dr. Gordon Lithgow of the Buck Institute for Research on Aging tells us about worms! Well, more accurately, his lab does research on nematodes, particularly an animal known as C. elegans. This unassuming scientific model has a lot of important advantages for science: they can be frozen and subsequently thawed and retain viability, they are extremely well understood down to the precise number of cells in their body and the wiring of their nervous system, known as the connectome. Additionally, they have a short lifespan and are cheap to work with. Why would that be advantageous, you may ask? This is where Dr. Lithgow's work on the Caenorhabditis Intervention Testing Program comes in. Short-lived organisms give Dr. Lithgow and his colleagues the opportunity to see how their biology responds to compounds in different contexts and to do so cheaply and rapidly. Think a vitamin, pharmaceutical or one of any number of other compounds may have a broad effect on longevity? Try it on Caenorhabditis first! Taking this approach allows the broad screening of compounds that might not otherwise get its chance in the limelight if science were limited to only working with rodents, for example. But what could nematodes possibly have in common with us? The answer to the question is... gene homology! In fact, around 35% of C. elegans genes have a corresponding human version. In this over 40-minute long conversation with professor Dr. Gordon Lithgow, we talk about... Nematodes... especially C. elegans, of course! The synergistic way in which research in lower organisms (C. elegans in this case) works together with rodent research to better understand the biology of aging and identify potential therapeutics. The story behind the Caenorhabditis Intervention Testing Program, a multi-institutional effort using the advantages of C. elegans short lifespan to screen for potential compounds that may increase lifespan. We also discuss the more expensive-but-closer-to-humans version of this program known just the Intervention Testing Program. The various qualities of C. elegans, especially as related to science's deep knowledge of the organism, that make it a perfect fit for this type of research. Some of the early experiences that actually lead to my early interest in the aging field and how it actually holds a bit in common with Gordon's story today. The role of protein aggregation as a possible fundamental mechanism of aging... even beyond its more established role in neurodegenerative diseases. Some of the fascinating research surrounding mild heat stress as a means to increase lifespan in lower organisms. Some of Gordon's research into the effects of metal accumulation, particularly iron, on aging in lower organisms and how, in humans, it may be important to approach the intake of these minerals with care. The interplay between genes that influence iron-binding and the development of Alzheimer's disease. Some of Gordon's research into the (perhaps surprising) effect of vitamin D on aging in C. elegans and, particularly, on the solubility of proteins... the loss of which is a feature of aging of particular interest. The critical involvement of the Nrf2 stress-response pathway in conferring benefits of vitamin D in worms... a pathway many of you may know about from previous discussions of sulforaphane, a robust activator of Nrf2 in humans. Some of the challenges encountered with ensuring standardization of protocols across all of the participating labs in the Caenorhabditis Intervention Testing Program. The amazing genetic diversity represented in soil-dwelling nematodes and how this is also an advantage in longevity research. The interesting possibility that certain compounds may have a different overall effect on lifespan or healthspan that is dependent within certain contexts (e.g. environmentally stressed or not). Learn more about Dr. Gordon Lithgow. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how you can support the podcast for as little or as much as you like. Have you done a 23andMe genetic test? You can learn more about whether you have some of the specific polymorphisms discussed in this podcast, including ones related to the hemochromatosis and transferrin genes, by clicking here.
If you're anything like me, having the facts straight can sometimes help you to push through the tough part of building new habits or breaking old bad ones. This podcast talks about the realities about what the science says surrounding the consumption of refined sugar. Some of the facts may surprise you! We talk about the relationship of consumption of refined sugar with... mortality and aging brain function, memory, and neuroinflammation the development of cancer and expression of oncogenes sex hormones ... and, of special relevance, if you're hoping to cut out a soda habit, the real addictive properties of refined sugar consumption that mirror that of more well-known drugs of abuse. Enjoyed this episode?Learn how to support the podcast by visiting our crowdsponsor page. Studies mentioned in podcast: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 10, 11, 14, 15, 16, 17, 18, 19
Today we try to answer or at least explore a big question in the world of health: does saturated fat cause heart disease? This is not an unreasonable concern given the fact that there have been several associative studies that have found a link between saturated fat and heart disease, which is, no doubt, a fat that we find abundantly in the typical American diet since it is richly found in staples like fatty beef, pork, butter, cheese, and other dairy products. And if you're in the United States and you're not at least a little concerned about heart disease, you may be asleep at the wheel since it's currently our leading cause of death. Studies mentioned in this episode: Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Visceral adiposity and metabolic syndrome after very high–fat and low-fat isocaloric diets: a randomized controlled trial. Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial. Personalized Nutrition by Prediction of Glycemic Responses. Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease. Added sugar intake and cardiovascular diseases mortality among US adults. Genetics resources: 23andme.com promethease.com foundmyfitness.com/genetics
Does meat consumption cause cancer? Or, put another way… does avoiding meat help prevent cancer? If you aren't already savvy to the topic, this may sound more absurd than it should. Here's why: there have been many, many, many correlative studies that have found that higher meat consumption is associated with a significantly higher risk of cancer and cancer mortality. To try to answer this question we end up going deep into discussing plausible mechanisms that might help explain this phenomenon and, indeed, discussing a little bit of cancer biology as well. Some of the publications mentioned in this podcast: Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality Effect of aerobic exercise on insulin, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in overweight and obese postmenopausal women Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3 Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. Functionally significant insulin-like growth factor I receptor mutations in centenarians Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies Changes in plasma somatomedin-C in response to ingestion of diets with variable protein and energy content
The World Health Organization estimates that more than 350 million individuals of all ages have depression and approximately one-third of all patients with depression fail to respond to conventional antidepressant therapies like SSRI’s. The good news is that today, perhaps more than ever, good science is starting to illuminate some of the underlying biological mechanisms surrounding the development of depression. This new understanding may soon help the clinical world develop new approaches to treatment that may be vastly more effective and for a greater number of people than the traditional approaches. Publications mentioned: Antidepressants versus placebo in major depression: an overview Inflammation: Depression Fans the Flames and Feasts on the Heat Association of high-sensitivity C-reactive protein with de novo major depression. Sex Differences in Depressive and Socioemotional Responses to an Inflammatory Challenge: Implications for Sex Differences in Depression Dopaminergic Mechanisms of Reduced Basal Ganglia Responses to Hedonic Reward During Interferon Alfa Administration Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward. Structural and functional features of central nervous system lymphatic vessels Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism Neurobiology: Rise of resilience First biological marker for major depression could enable better diagnosis, treatment Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial Sweetened-Beverages, Coffee, and Tea in Relation to Depression among Older US Adults (P05.122) Consuming highly refined carbohydrates increases risk of depression
Dr. Roland R. Griffiths is a clinical pharmacologist at Johns Hopkins and has been researching mood-altering compounds for over 40 years. As an unusually prolific scientist, having published over 360-times, he's also responsible for having started the psilocybin research program at Johns Hopkins nearly 2 decades ago. In this 1-hour and 15-minute podcast, we discuss… 00:01:03 - the broader story of Dr. Griffiths 40 years of mood-altering drug research, including what got him started and how taking up a meditation practice ultimately influenced the eventual focuses of his research. 00:02:22 - the effect psilocybin has had in clinical trials in eliciting so-called mystical experiences that can act as a long-term catalyst for meaningful spiritual change and is amenable to being reproduced and clinically studied in a prospective manner. 00:03:45 - what distinguishes psilocybin from other drugs, particularly when reflecting backward on the experience months afterward. 00:05:11 - the process by which Dr. Griffiths and his team create an appropriate “setting” and facilitate feelings of safety for those participating in his trials. 00:06:42 - the elusive fundamental nature of a classical psychedelic experience whereby people often simultaneously describe the experience as ineffable (indescribable) but yet also often assign it a truth value that may even exceed that of everyday consensus reality. 00:07:36 - a description of the core features of a classical mystical experience that overlap with those found in a mystical experience induced by psilocybin. 00:08:58 - the qualities of the experience that Dr. Griffiths believes to most underlie the “reorganizational” potential it can have. 00:10:55 - the interesting potential areas for scientific exploration that the reproducibility of the psilocybin experience makes the substance amenable to. 00:11:25 - the promise psilocybin has shown as an effective therapeutic for anxiety and depression in patients with life-threatening cancer and also treatment-resistant depression in otherwise healthy patients (00:18:46). 00:13:04 - the lack of rigor in the very early trials on these compounds and the way in which cultural stigma surrounding psychedelic drugs ultimately played a role in impeding real, substantive clinical research for decades afterward. 00:16:31 - the long-term resilience of the antidepressant and anxiolytic effect, lasting six months and possibly even longer. 00:21:01 - the effect psilocybin has demonstrated in animal studies to increase hippocampal neurogenesis and enhance extinction of trace fear conditioning. 00:23:07 - the somewhat unintuitive neurobiological mechanism that may tie together some of the antidepressant properties of both psilocybin and ketamine, an anesthetic currently being studied as a rapid-onset antidepressant. 00:25:16 - whether or not the mystical subjective experiences are necessary for drugs like psilocybin to exert their antidepressant or anxiolytic effects. 00:26:43 - what the default mode network is and what its pattern of activity is in depression, long-term meditators, and after the acute use of psilocybin. 00:32:16 - the hard problem of consciousness. 00:37:26 - the challenge of finding the neurological correlates to match the phenomenology of individual’s subjective experiences. 00:38:16 - the promise psilocybin has shown in a small trial on smoking cessation where 60% of the treatment group were still abstinent a year afterward and plans Dr. Griffiths has to expand this area of research 00:41:10 - the possibility that the “reorganizational nature” of these experiences may open up new avenues as trials continue to try to embed the experience within different therapeutic contexts. 00:44:02 - the roadmap to FDA approval for use of psilocybin as a medication, particularly in the context of cancer-associated depression and anxiety. 00:45:05 - the risks inherent in taking psilocybin and the frequency of self-reported negative experiences in the general population. 00:47:22 - the criteria Dr. Griffiths and his colleagues use when screening for volunteers to participate in his studies involving psilocybin. 00:49:21 - the inability for clinicians to predict who is at risk of having challenging experiences defined by fear and anxiety (“bad trip”) and whether or not it is desirable, in terms of achieving a therapeutic outcome, to prevent these types of experiences altogether or not. 00:51:43 - the sort of dosages used in the trials. 00:54:45 - the clever ways devised by Dr. Griffiths to placebo control trials where expectation itself can affect outcome. 00:57:45 - some of the interesting anecdotes gleaned from Dr. Griffiths’ working with long-term meditators participating in the psilocybin trial. 01:05:13 - a brief discussion about some of the other psychedelics besides psilocybin, such as salvia divinorum and DMT (at 01:10:24). 01:12:08 - the historical indigenous use of psychedelics in various cultures spread throughout the world. Watch this as a video on YouTube.
Dr. Jed Fahey is a multi-decade veteran of isothiocyanate research and is the director of the Cullman Chemoprotection Center at Johns Hopkins University. Much of this conversation, as you might expect given Dr. Fahey's pedigree as a research scientist, is focused on isothiocyanates and, indeed, sulforaphane! While we covered quite a lot on this very topic (isothiocyanates) via my solo podcast a few weeks ago, this covers everything that may have been overlooked.... and, indeed, so much more! Skip to the timeline below for a sampling. Dr. Fahey and his colleagues have been, in a big way, at the absolute center of what is a staggering amount of research on these very powerful compounds. There is hardly a topic which we can discuss in which he doesn't have an anecdote about a study he was involved in, or, in some cases, tribal knowledge that may not even be published but is nonetheless interesting and an important part of the story that is unique to his particular vantage point. In this 2-hour and 30-minute interview, we discuss... 00:00:00 - the early history of sulforaphane research, including key initial discoveries. 00:00:37 - the serendipitous unfolding of events that lead to the converging of the research on the NRF2 stress response pathway with the sulforaphane-related research going on at the same institute Johns Hopkins. 00:05:06 - why cruciferous vegetables bother to create isothiocyanates in the first place. 00:07:26 - the involvement of the heat shock proteins, in addition to the increased activity of Nrf2, as an additional cellular response mechanism that's been observed in association with sulforaphane. 00:08:11 - how sulforaphane affects a diverse array of biochemical processes from glutathione synthesis to elimination of reactive oxygen species and detoxification of harmful compounds, including carcinogens. 00:15:01 - whether or not to cook your cruciferous vegetables. 00:15:34 - the epidemiological (associative) evidence that cruciferous vegetable consumption may help reduce the risk of cancer. 00:18:30 - the extremely unpredictable nature of endogenous conversion of glucorapahanin (the precursor) into sulforaphane between person to person. 00:22:14 - practical information surrounding supplementation of sulforaphane. 00:27:05 - the effect one particular french sulforaphane supplement had on the doubling rate of PSA, which is a marker for prostate cancer recurrence in prostate cancer patients. 00:28:17 - the role that the Cullman Chemoprotection Center at Johns Hopkins has played, in addition to fundamental research, in providing early, vital infrastructure enabling some of the efforts of the international research community in elucidating the effects of sulforaphane and related compounds and the underlying biological pathways. 00:28:26 - the incredible, almost geometric growth in new studies that has occurred since the advent of a few of the key discoveries about sulforaphane and its method of action. 00:32:48 - the practicality of probiotics as a way to improve endogenous myrosinase activity needed to convert the precursor to sulforaphane into the bioactive sulforaphane. 00:33:26 - the involvement of our gut bacteria in our ability to convert the precursor of sulforaphane into its active form. 00:37:13 - whether or not endogenous myrosinase activity improves as a function of repeated challenge with glucoraphanin (the precursor to sulforaphane). 00:39:30 - why probiotics may vary in their degree of efficacy. 00:43:00 - why consuming isothiocyanates to reduce the number of bacterial colonies of h. pylori, a risk factor for peptic ulcers and stomach cancer, may turn out to be a better intervention than complete eradication of the species with antibiotics. 00:47:21 - the bizarre relationship h. pylori has with childhood asthma, where it has been shown that having some h. pylori seems to reduce asthma incidence in childhood. 00:52:28 - the effect sulforaphane has on inflammation and why inflammation is often a great therapeutic target for many different diseases, including diseases of aging. 00:54:05 - the life extension properties broccoli has been shown to have in an insect model of aging. 00:59:27 - the underlying causes of Hutchinson-Gilford progeria and the promise sulforaphane may hold for this disease of rapid aging. 01:09:00 - the effects of sulforaphane or Nrf2 activation on diseases of the brain, such as autism (human evidence) and Alzheimer's (animal evidence), possibly through anti-oxidative or anti-inflammatory effects. 01:11:09 - the so-called autistic fever response whereby autistic patients report a sudden reversal of symptoms during brief periods of fever. 01:10:05 - the role heat shock proteins might play more broadly in the prevention of certain neurological diseases. 01:19:00 - the challenges inherent in clinical trials where scientists may be extremely optimistic about the effects that might be observed, but still have to exercise caution and choose trial conditions that may be conservative, for the good of the people whose lives and hopes hang in the balance. 01:27:01 - the role of inflammation and depression and what some studies on animals have demonstrated in terms of sulforaphane's potential as an antidepressant. 01:42:30 - a special isothiocyanate-containing plant known as Moringa or sometimes referred to as the drumstick tree or the horseradish tree. 01:46:32 - Dr. Fahey's inadvertent foray into the consumption of exotic meats during a visit to Africa. 01:51:15 - a compound commonly associated with broccoli: indole-3-carbinol and its downstream product diindolylmethane (DIIM). 01:57:00 - the practicality of using mustard seed powder as an extra source of myrosinase, possibly for your cooked cruciferous vegetables. 02:00:13 - whether or not it makes sense to freeze broccoli sprouts in order to extend their shelf life, and possibly even increase sulforaphane within certain contexts. 02:05:25 - Dr. Fahey's thoughts on where endogenous conversion of glucoraphanin occurs in the body, as well as how long it takes before sulforaphane metabolites hit the bloodstream after ingestion. 02:07:25 - Some general thoughts on frequency in terms of how often one might need to take sulforaphane to elicit its biological effects. 02:12:16 - why sulforaphane may one day be a component of sunscreen. 02:12:31 - what some of the upcoming trials involving sulforaphane are at the Cullman Chemoprotection Center. 02:17:07 - the incredible way in which a sulforaphane-rich broccoli sprout beverage was shown to dramatically enhance the detoxification of benzene through excretion: one study showed up to 61% starting immediately after supplementation. You can find out more about Dr. Fahey and the Cullman Chemoprotection Center by visiting: The Cullman Chemoprotection Center Website (donation link) facebook.com/chemoprotectioncenter twitter.com/jedosan (Jed's twitter) jedfahey.com
This podcast is about one of the most important biological pathways you could possibly take the time to learn about: the NRF2 pathway. The most potent naturally-occurring inducer of this pathway, a plant compound known as sulforaphane, may be one of the most potent health-enhancing compounds at our disposal and yet... no one is keeping it out of your hands! No $1,000 per pill markup is keeping it out of your hands -- it’s available to anyone willing to take the little bit of time it takes each week to produce broccoli sprouts. In some respects, broccoli sprouts may even be a great equalizer in a way... while it’s true that healthy food can often be expensive, it’s even reasonably possible for a person to take $20 worth of seeds and feed their whole family some of the most healthful greens you could get your hands on. This video will tell you why. Here are a few of the more salient points surrounding sulforaphane that are discussed in this podcast... Profound changes in lipid biomarkers, reducing heart disease risk by as much as 50% in humans. Massive reductions in cancer risk in humans and also highly effective as a cancer intervention, particularly prostate and breast but also many others. Steep reductions in inflammation in humans. Shown in mice to be as effective as prozac as an anti-depressant. Steep behavioral changes in humans with respect to certain neurological disorders, such as autism. Causes dramatic boosts in the excretion of air pollutants (up to 60%) in humans. Key sections you may want to skip to: 00:03:35 - Cancer and mortality 00:21:56 - Aging 00:29:37 - Brain and behavior 00:41:33 - Final recap 00:44:18 - Dose NOTE: If you enjoy this podcast, you'll enjoy the YouTube video more since it shows all of the figures and citations.
This episode of the FoundMyFitness podcast features Dr. Valter Longo, a professor of gerontology and biological sciences and director of the longevity institute at the University of Southern California. Dr. Longo has made huge contributions to the field of aging, including the role of fasting and diet in longevity and healthspan in humans as well as metabolic fasting therapies for the treatment of human diseases. In this podcast, Valter and I discuss... The effects of prolonged fasting, which refers to 2-3 day fasting intervals in mice and 4-5 days in humans. Dr. Longo’s work on the fasting-mimicking diet, which is 5 day restricted diet that is meant to simulate some of the biological effects of prolonged fasting while still allowing some food. How clinical trials have demonstrated efficacy for this diet for type 2 diabetes, multiple sclerosis, and cancer patients. Fasting as an inducer of differential stre�ss resistance, where it can simultaneously make cancer cells more sensitive to death while also making healthy cells more resistant to these same death stimuli (such as chemotherapy) which might otherwise induce cell death amongst healthy cells as collateral damage. Fasting as a biological state which humans historically experienced with extreme regularity and we may ultimately need in order to mitigate various disease states. The effects of prolonged fasting on the immune system, namely, how it clears away damaged white blood cells via autophagy and how this causes hematopoietic stem cells to self renew and make more stem cells and also produce new blood cells to fully replenish the white blood cell population. How prolonged fasting causes a shift in the immune cell population towards one that is more representative of youth by normalizing the ratio of myeloid cells to lymphoid cells. The positive effects of prolonged fasting and the fasting-mimicking diet on markers of systemic inflammation, blood glucose levels and other aging biomarkers. The conclusions of Dr. Longo & Dr. Marcus Bock’s research comparing 1 week of the fasting-mimicking diet followed by 6 months of mediterranean diet to six months of a ketogenic diet in people with multiple sclerosis. The strange, somewhat paradoxical role of autophagy genes in cancer progression and some of the open questions surrounding the exact role that these genes are playing. Dr. Longo’s high level thoughts on metformin as an anti-aging drug. How the growth hormone/IGF-1 axis is one of the most important genetic pathways in aging from yeast to worms to mice to humans. You can learn more about the fasting-mimicking diet by visiting prolonfmd.com and you can receive an email when Dr. Longo published his upcoming book (English version) by following his profile on Amazon.
Today's episode features Dr. Ruth Patterson, a professor in the UC San Diego Department of Family Medicine and Public Health as well as Associate Director of Population Sciences and leader of the Cancer Prevention program at Moores Cancer Center at UC San Diego Health. If you enjoyed my last episode with Dr. Satchin Panda, I have good news! This will also be a great episode for you, since we talk about some similar ideas, but focus more on the human side of things, especially when it comes to time-restricted eating, since Dr. Patterson does primarily clinical research. In this 45-minute podcast, we talk about... The importance of time-restricted eating as a practical public health intervention, mostly for it's ease of implementation, that may have a widespread impact on disease risk. Why you should probably make sure your time-restricted eating window occurs earlier in the day, rather than later. How the first 5% drop in weight loss can have disproportionately large effects on the metabolic factors associated with breast cancer risk when compared with subsequent weight loss. The association of longer fasting durations beginning earlier in the evening and improved sleep in humans, as well as spontaneous physical activity in their day-to-day lives. The relationship between metabolism and breast cancer risk. The effect of lifestyle factors, such as obesity, physical activity, what and even when you eat, whether or not you smoke tobacco... and how even modest changes, such as consuming food earlier in the day and only during an 11-hour window, can decrease breast cancer risk and recurrence by as much as 36%. The importance of starting your fast earlier in the evening, and how an earlier eating window has been shown to correlate to reductions in inflammatory markers. The association of higher circulating insulin levels with breast cancer risk, and how insulin itself has an important relationship with estrogen by affecting the levels of sex-hormone binding globulin. The dangers of having a cellular environment that is inflamed, as the case is with the obese, and simultaneously having elevated cellular growth signals, which is also characteristic of the hormonal milieu of the obese. The surprisingly small role heredity plays in determining overall risk of breast cancer when compared to lifestyle factors. How healthful lifestyle habits, like choosing to eat during the right window, ultimately helps us trend our risk for many of the diseases of old age in the correct direction instead of influencing only one or another. If the concept of time-restricted eating especially piques your interest, make sure to... Check out the podcast released just prior to this one: Dr. Satchin Panda on Time-Restricted Feeding and Its Effects on Obesity, Muscle Mass & Heart Health. Make sure your data points go to good use! Visit myCircadianClock.org to learn how you can, by committing to a minimum of a 14 week "intervention" and submitting pictures of your food from your iPhone or Android phone, move human research on time-restricted eating forward. Huge special thanks to Dr. Ruth Patterson for coming on. Enjoy the podcast!
Dr. Rhonda Patrick speaks with Dr. Satchin Panda, a professor at the Salk Institute for Biological Studies in La Jolla California. Satchin's work deals specifically with the timing of food and it's relationship with our biological clocks governed by circadian rhythm and also the circadian rhythm in general. In this video we discuss... The fascinating history of experimentation that ultimately elucidated the location for the region of the brain necessary for a properly timed sleep-wake cycles. The relationship between our body's "master clock" and it's many peripheral clocks. Why infants sleep so intermittently, instead of resting for a longer, sustained duration like healthy young adults... and why this sustained rest also goes haywire in the elderly. The fascinating work Dr. Panda took part in that lead to the discovery of a specialized light receptor in the eye that sets circadian rhythms and is known as melanopsin. The important relationship between the relatively light insensitive melanopsin, which requires around 1,000 lux of light to be fully activated, and its control of the circadian clock by means of activation of the suprachiasmatic nucleus and suppression of melatonin. The effects light exposure seems to have on next-day cortisol, a glucocorticoid hormone that regulates around 10-20% of the human protein-encoding genome. The clever experimental design by which Dr. Panda and his colleagues discovered that certain circadian rhythms, especially of the liver, are entrained by when we eat, instead of how much light we get. This underlines the fact that, when managing are circadian rhythm, both elements are important! One of the more surprising effects of time-restricted feeding in mice eating a so-called healthy diet: increases in muscle mass and even endurance in some cases. Interested in trying out time-restricted feeding? Don't let your data points go to waste! You can try out time-restricted feeding and have a real impact on human research! Commit to 14 weeks and download Dr. Panda's mobile app to get started. Learn more at: mycircadianclock.org/participant
Dr. Rhonda Patrick speaks with
Ray Cronise, a former NASA material scientist and cofounder of zero
gravity, a company that offers weightless parabolic flights to
consumers and researchers. In this episode, coming at the tail end
of a rather extreme 23-day water fast for Ray, we discuss, perhaps
unsurprisingly, some of the benefits that are associated with
fasting! Ray talks about
shifting one's perspective from looking at nutrition only through
the lens of meeting day-to-day nutritional needs, and instead, also
considering optimizing metabolism for longer-term effects as
well, the importance of
thinking about longevity in the context of functional healthspan,
some of the similarities between the body’s physiological response
to heat stress, cold stress, and exercise and so much
Learn more about Ray Cronise by
visiting his website at hypothermics.com
(raycronise.com) or by saying hello on twitter: twitter.com/raycronise.
Finally, Ray also has a book
available for pre-order called "Our
This podcast is with Dr. Dominic D'Agostino, an assistant professor at the University of South Florida in Tampa and all around expert on ketosis.
In this podcast we discuss...
* Dom's efforts at teasing out the differences between induced nutritional ketosis (through a low carbohydrate, high fat diet) and ketosis from the dietary introduction of exogenous ketones, like beta-hydroxybutyrate, especially in the context of therapeutic and performance enhancing effects.
* His work on formulating ketone esters.
* The differences in tolerability between MCT (medium chain triglycerides) powders versus liquids, as well as the amount of supplemental MCT a person would need to consume in order to achieve mild ketosis without carbohydrate restriction.
* The differences between different types of ketogenic diets.
* The modified atkins diet which has been demonstrated to have similar efficacy to the classical ketogenic diet in the treatment of drug-resistant epilepsy and how it may be a slightly more practical option for achieving therapeutic nutritional ketosis.
* The importance of making the correct carbohydrate choices, even and maybe especially in the context of a ketogenic diet, with a diverse variety of raw vegetables being the most favorable.
* What keto adaptation is and what it means, at a physiological level, to be keto adapted and how this is distinguished from short periods of ketosis we experience in our day-to-day lives.
* Some of Dom's ideas around cycling various dietary strategies as a way of promoting metabolic flexibility.
* How ketones, when used as a source of energy, may result in a net reduction in the number of damaging reactive byproducts known as reactive oxygen species than what may be produced by other forms of energy metabolism while also producing more ATP from, proportionately, the same amount of oxygen.
... AND SO MUCH MORE. OH MY LORD THERE IS SO MUCH MORE. Enjoy!
This podcast is with Dr. Peter Attia. Peter is the founder of Attia Medical, a medical practice with offices in San Diego and New York City, focusing on the applied science of longevity and optimal performance.
You may have first heard about Dr. Attia from his two interviews that have been on the Tim Ferriss show, or from any number of popular presentations he's given that were filmed and put online. In addition to being a medical doctor, Dr. Attia has done research on the role of regulatory T cells in cancer regression and other immune-based therapies for cancer. Regulatory T cells have also been, in the past, referred to as suppressor T cells because of their role in actually attenuating or reducing the inflammatory response.
Dr. Attia and I share interests in all things related to longevity and healthspan, which includes the role of diet, nutrition, sleep, exercise, and stress. Dr. Attia is a medical doctor and specializes in implementing these strategies in clinical practice. You can learn more about that at his website www.attiamedical.com.
This podcast has a 20-page report associated with it! Get it now at foundmyfitness.com/cryotherapy. Dr. Rhonda Patrick explains how cold shock is a type of hormesis, which is a description of a type of stress that, in the right doses, is enough to shock the body and kick off adaptive processes and response mechanisms that are hardwired into our genes, and, once on, are able to create a resilience that actually exceeds what was needed to counter the initial stimuli. Rhonda discusses how cold exposure increases norepinephrine up to 5-fold in the brain and what the temperature and duration needed to do this are, how norepinephrine has an affect on mood, vigilance, focus, and attention, how cold exposure increases cold shock proteins including one in the brain that repairs damaged synapses and in muscle prevents atrophy, how cold-induced norepinephrine lowers inflammation and pain by decreasing the levels of 3 inflammatory mediators, how chronic cold shock may increase immune cell numbers and particularly a type of immune cell that kills cancer cells, how cold exposure increases metabolic rate, the number of mitochondria, and the burning of fat, what the effects of different cold exposure temperatures and timing are on athletic performance, recovery time, and muscle mass, and the differences between various types of cold shock modalities, including cold water immersion and whole body cryotherapy.
This podcast features Rich Roll. Rich is an author, a podcaster ("Rich Roll Podcast" on iTunes), as well as founder and first person to complete the EPIC5 Challenge. The EPIC5 challenge involves completing 5 Full Iron Distance triathlons on 5 Hawaiian islands in under a week. Rich has also been a repeated top finisher in the Ultraman World Championships in Hawaii, which is a three-day, 515km (320 mile) annual endurance race held on the Big Island of Hawaii. The race is divided into three stages over three days: The first is a 6.2 mile (10-km) ocean swim, followed by a 90-mile (145-km) cross-country bike ride, with vertical climbs that total 6,000 feet. Stage two is a 171.4-mile (276-km) bike ride, with total vertical climbs of 4,000 feet. Finally, stage three is a 52.4-mile (84-km) double marathon. Each stage must be completed within 12 hours or less. You can read about Rich's journey to Ultraman competitor in his book, "Finding Ultra: Rejecting Middle Age, Becoming One of the World's Fittest Men, and Discovering Myself."
In this episode, Dr. Rhonda Patrick chats with Dr. Darya and Kevin Rose. They chat about Darya's fascinating experience on a 10-day silent meditation retreat where she spent around 7 hours a day doing seated meditation, intermingled with another 6 hours a day of walking meditation. They discuss the biological significance of mindfulness while eating, unlocking the mysteries of blood glucose by actually testing your response to foods, or, in Kevin's case, alcoholic beverages. Kevin talks about his experiments with a ketogenic diet featuring large amounts of vegetables combined with fats to drive his ketosis and other ideas and projects he is working on. They also discuss how intermittent fasting and how intermittent fasting functions as a beneficial hormetic stressor that activates gene expression changes that can actually make you more resilient and much more!
Dr. Rhonda Patrick interviews Dr. Pierre Capel, professor emeritus in experimental immunology at the Utrecht University in the Netherlands where he researched a wide range of topics from genetic modification to cancer immunotherapy. Pierre also works with Wim Hof, otherwise known as the iceman (guest on the last podcast) who is especially well-known for some of his amazing physical feats, like staying in a tub with direct contact to ice for over an hour and fifty three minutes. Pierre explains some of the science behind how Wim is able to withstand cold temperatures for prolonged periods of time. The explanation comes down to what the 2014 PNAS study on Wim's technique showed: that reductions in carbon dioxide temporarily increased blood pH. The missing piece to the puzzle that Pierre brings in is the simple fact that pain receptors that are critical to feeling cold temperatures actually rely on what are known as "acid sensing ion channels", which have been shown in other studies to become inactive within
the pH ranges Wim and his trainees are able to increase their blood to.
In addition to talking about some of the thermo- and pain- receptor stuff, Pierre and Rhonda also discuss other cool literature he's familiar with, including:
1.) Good stress and bad stress and how meditation affects the expression your genes.
2.) Meditation and the speed with which it affects fMRI changes.
3.) How even loneliness can change gene expression, including some involved in metabolism, inflammation, and the endocrine system.
4.) The effect of social isolation in mice on cancer metastasis, and conversely how wound healing can be affected in mice just by changes in their environment.
5.) What affects the stress hormone cortisol has on gene expression.
6.) What the inflammasome is and how its activation can be linked to the central nervous system.
7.) How the limbic system regulates emotions (and this is not easily controlled) but meditation has been shown to help control the limbic system.
Dr. Rhonda Patrick interviews Wim Hof also known as the "Iceman." Wim holds the world record for the longest ice bath (1 hour and 53 minutes and 12 seconds), just to name one of his many impressive feats. Dr. Patrick and Wim talk a bit about Wim's back story that culminated in him trying out cold water immersion, the relatively recent 2014 scientific publication of the “Wim Hof Method” which includes cold exposure during training, exposure to bacterial endotoxin, Wim's breathing techniques, and meditation (http://www.ncbi.nlm.nih.gov/pubmed/24799686).
The 2014 study demonstrated the effects of just 4 days of training with the “Wim Hof method” on 12 volunteers injected with bacterial endotoxin. Some of the effects include: increased epinephrine, norepinephrine, increased anti-inflammatory cytokines (IL-10), decreased pro-inflammatory cytokines (TNF-alpha), increased blood ph to 7.75 (in some cases), and decreased carbon dioxide blood levels. The results of this study hint at some very interesting possibilities that might explain why Wim's technique helps him to endure the cold more, as well as how he was able to suppress his inflammatory response to endotoxin himself.
In this audio recorded Oct. 3rd, 2015, Dr. Rhonda Patrick delivers the keynote lecture at the Orthomolecular Medicine Congress in Bussum, Netherlands (MBOG Congres 2015).
Discussion includes how micronutrient inadequacies are very prevalent, and how her mentor, Dr. Bruce Ames, found that the body does a strategic rationing so that those proteins and enzymes in the body which are essential for short-term survival get their share of vitamins and minerals at the expense of other proteins and enzymes that are essential for long-term survival. This results in insidious types of damage and may lead to diseases of aging such as cancer and neurodegenerative diseases.
She also discusses her ongoing clinical research on the role of DNA damage in cancer and aging and how her data shows that obese individuals have much more DNA damage than lean individuals, her recent research on how vitamin D is needed to produce serotonin in the brain and how this may be relevant for the prevention of autism because serotonin shapes the structure and wiring of the developing fetal brain. Finally, she talks about her research on how omega-3 fatty acids regulate serotonin release from neurons and receptor function and how vitamin D and omega-3 fatty acids are important to prevent brain dysfunction particularly in individuals that have gene polymorphisms in the serotonin pathway that predispose them to low serotonin.
In this podcast I discuss some of the mechanisms by which chronic stress (and rumination) affect the brain and brain aging, the gut and inflammation, the immune system, and biological aging through acceleration of telomere shortening. I talk about how meditation can buffer these negative effects of stress and improve cognitive performance, brain aging and biological aging in general. Get the free report: foundmyfitness.com/meditation-report
In this episode Rhonda talks about how heat stress from using the sauna makes the body more resilient to the stresses of aging, possible reasons why one study associated sauna use with up to a 40% lower all-cause mortality as well as a 50% lower cardiovascular disease related mortality, how it enhances athletic endurance, staves off muscle atrophy, improves regrowth of muscle after disuse, and some of the profound effects on the brain, including the growth of new brain cells, improvement in focus, learning, and memory, and even potentially ameliorating depression and anxiety. She also talks about how BPA, PCBs, phthalates, and other metals are excreted through sweat. In addition, she addresses some practical applications like temperature and duration in the sauna, the difference between a dry, wet and infrared sauna, sauna timing, as well as other forms of heat stress such as steam showers, hot baths, and hot yoga.
Dr. Justin Sonnenburg is an associate professor of microbiology and immunology at Stanford and Dr. Erica Sonnenburg is a senior research scientist in the Sonnenburg lab where they research many aspects the interaction between diet with the 100 trillion or so bacteria in the gut (specifically the colon) and how this impacts the health of the host (which in this case is a laboratory research mouse). In this episode we discuss the pivotal role fiber plays in fueling good bacteria in the gut to produce compounds that regulate the immune system including increasing the number of T regulatory cells, which are specialized types of immune cells that keep the immune system in check and prevent autoimmune responses, and how these compounds also increase other types of blood cells in the body in a process known as hematopoiesis. We also talk about how the lack of fiber in the typical American diet actually starves these good bacteria of their food. This has an effect not only on the immune system and autoimmune diseases but also results in the breakdown of the gut barrier, which leads to widespread inflammation and inflammatory diseases. Lastly, in this podcast, Dr. Erica Sonnenburg talks about how C-sections, have a negative effect on the infant’s gut due to the lack of exposure to bacteria present in the mother’s vaginal canal, and how the use of formula deprives the infant not only from the good bacteria present in Mom’s gut but also from special carbohydrates in breast milk that are good for the infant gut flora known as HMOs or human milk oligosaccharides.
Dr. Ronald Krauss, M.D. is the director of atherosclerosis research at Children’s Hospital Oakland Research Institute, Adjunct Professor at UCSF and UC Berkeley. Dr. Krauss is really one of the pioneering scientists that changed the way we all think about cholesterol and saturated fat. He developed an assay that allows the quantification of low density lipoprotein particle size and concentration (known to the wider world as LDL cholesterol) based on a technique which determines the size of the particle based on physics...meaning the speed at which it flies through the air. In this episode, Rhonda and Ron discuss what HDL and LDL cholesterol are, what they do in the body and how they play a role in heart disease. We talk about what small, dense LDL particles are, how they form, what effect eating saturated fat versus refined carbohydrates have on LDL particle size and heart disease risk and more generally what the main risk factors for heart disease are. Ron also talks about the good, bad and the ugly of LDL-lowering drugs known as statins and much more.
Meet some of the CHORI bar team: Dr. Bruce Ames, Dr. Joyce McCann, and Dr. Mark Shigenaga. On this podcast we talk about the different types of HDL and LDL cholesterol and what they do in the body. We discuss a low-calorie, micronutrient- and fiber-dense nutrition bar (referred to as the CHORI bar) that Bruce and I briefly touched on in a previous conversation, how each of the components of the bar from the vitamins and minerals to the fiber and polyphenols are all really important but have separate functions in the body that can work together in much the same way an orchestra play their individual parts to create a symphony that is larger than their individual roles, how the chori bar raised a certain type of HDL in lead adults in just two weeks, how eating the CHORI bar raised HDL, lowered triglycerides and small LDL particles, and improved insulin sensitivity after eight weeks in overweight/obese individuals all without them changing their diet. The chori bar is not available for consumers yet but you can keep up with choribar updates on bruceames.org/choribar
Dr. Aubrey de Grey is a biomedical gerontologist and the founder of the SENS research foundation which aims to find technologies that can repair the various types of damage that occur during the aging process. In this episode Rhonda and Aubrey discuss the types of damage that cause aging, how aging results in a decrease in the capacity to repair damage, what role epigenetics play in aging, how people age at different rates, chronic inflammation as a driver of aging, factors that are in young blood that repair damage, the role of nutrition in aging, and recent technologies such as CRISPR, induced pluripotent stem cells that will advance anti-aging research and more. You can find Aubrey on twitter at @aubreydegrey, and his foundation at www.sens.org.
Dr. Rhonda Patrick answers some of the most popular questions regarding vitamin D including:
- How she decides how much vitamin D to supplement with
- Can you get too much vitamin D
- Is there a difference in vitamin D made from the sun versus a supplement
- What form of vitamin D is more bioavailable or absorbed better.
Dan Pardi is a Ph.D candidate that researches sleep neurobiology at Stanford and University of Leiden. He is also co-founder of Dan’s Plan, an online wellness and technology company. In this podcast Rhonda and Dan discuss what the determinants of good sleep are including duration, timing and intensity,the major causes of less sleep in our society, the consequences of sleep loss including decreased purging of toxic substances from the brain, damage to neurons that signal to the brain to stay awake (and how this leads to that feeling that you need coffee in the morning), increased incidence of chronic diseases such as cancer and type 2 diabetes, cognitive and behavioral impairments, the impact on eating behaviors and weight gain. We also discuss what the optimal amount of sleep is, the importance of sleep timing, and keeping the same schedule as well as other ways to improve sleep.
Tim Ferriss, notorious self-experimenter, three-time New York Times bestselling author, an angel investor, startup advisor, and much, much, much more. Full audio transcript available at: http://wwww.foundmyfitness.com/timtranscript
Jim Kean is the CEO of National Pro Grid League (NPGL) and founder of WellnessFX. In this podcast Rhonda and Jim discuss the quantified self movement and the importance of measuring biomarkers more than once, the gut's role in cholesterol and serotonin in the gut versus in the brain, about the role of exercise in preventing neuroinflammation and the effects of overtraining on sex hormones, a bit about the psychology of constructing a new, non-gender segregated, team spectator sport and bringing it to market, the factors that separate a professional spectator sport from any other form of entertainment: including patriotism, justice, and vicariousness, the mathematical nature of the sport and the floor coach's role in monitoring athletes before they start "redlining," how NPGL teams may find new ways to tune their gameplay and find an edge on the competition in the future by stepping up the use of more advanced athlete-level analytics.
Dr. Rhonda Patrick speaks with Dr. Bruce Ames, about a micronutrient- and fiber-dense nutrition bar (referred to as the CHORI bar) that was developed in the Ames laboratory. The bar was formulated to be moderate in calories (107 kcal/≈25 g bar), but nutrient dense, with a polyphenolic-rich matrix of fruit, walnuts, and non-alkali-processed dark chocolate, supplemental vitamins, minerals, docosahexaenoic acid (DHA), a blend of insoluble and soluble fibers, protein, and glutamine. Most vitamins and minerals are present in amounts representing 10 to 50% of their corresponding recommended daily allowance (RDA) per bar; with the exceptions of vitamin D and vitamin C (both added above 50% RDA). The goal was not to meet the RDA in every case but to complement standard dietary intakes by consumption of 2 bars each day. People that ate the bar were told not to change their diets but just to eat the bars on top of their normal diet.
Lean people that ate the CHORI bar twice a day were able to raise HDL, lower homocysteine, and raise glutathione in just two weeks. Overweight/obese people with low inflammation that ate the bar showed weight loss after 8 weeks, raised their HDL, lowered triglycerides and small LDL particles, and improved insulin sensitivity. Overweight/obese people that had high inflammation were able to lower their inflammation after 2 weeks of eating the bar and raise their HDL after 8 weeks.
In this podcast Dr. Rhonda Patrick interviews Dr. Bruce Ames about his triage theory, which he proposes that the body has developed a rationing response to shortages of micronutrients (vitamins and minerals) throughout evolution. When cells run out of a vitamin or mineral, that scarce micronutrient is allotted to proteins (in the body) essential for short-term survival. Proteins needed for long-term health, including those that protect DNA, lose out and become disabled and lead to diseases of aging. In addition they discuss how RDAs are chosen and what Bruce calls “longevity vitamins” which he calls a class of nutrients that exist mostly to prevent degenerative diseases of aging in addition to essential vitamins and minerals.