Charles Raison

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 episode, you'll discover:

• (00:00) Introduction
• (06:26) Role of inflammation in depression
• (10:08) Evolutionary mechanism
• (16:19) Genetics of depression
• (22:57) How obesity causes depression biochemically
• (33:32) Does exercise treat depression
• (36:08) Hyperthermia as treatment
• (46:08) Inflammation promotes depression
• (53:39) Did we evolve to need hormetic stress?
• (01:03:38) Heat-shock proteins
• (01:06:10) Repurposing ancient wisdom
• (01:17:31) Psychedelics and meditation
• (01:27:51) What is the role of conventional pharmacotherapy?
• (01:35:19) Lifestyle modifications for depression
• (01:42:21) Why light and circadian rhythm are important for mental health

If you're interested in learning more, you can read the full show notes here.

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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.

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Eric M. Verdin

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, you'll discover:

• (00:00) Introduction
• (07:32) Interventions to prolong lifespan
• (10:42) The role of insulin pathways in aging
• (16:25) HDAC inhibition by ketones
• (27:52) Protein activates mTOR & IGF-1
• (30:28) PPAR-alpha activation facilitates benefits of a ketogenic diet
• (35:28) What biomarkers can predict aging?
• (39:38) Cellular NAD+ levels decrease with age
• (52:47) Ketogenic diet safety
• (56:07) Intermittent fasting as an alternative to a keto diet

If you're interested in learning more, you can read the full show notes here.

Join over 300,000 people and get the latest distilled information on ketogenic diet & longevity straight to your inbox weekly: https://www.foundmyfitness.com/newsletter

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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.

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Dr. Satchin Panda

Dr. Satchidananda (Satchin) Panda is a professor in the Regulatory Biology Laboratory at the Salk Institute for Biological Studies.

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...

• (00:00) Introduction
• (05:36) What is time-restricted eating
• (09:41) Circadian rhythm and eating times
• (16:05) Dr. Panda's eating window
• (20:52) Crowdsourced research uses mobile app to collect data
• (24:34) TRE reduces inflammation
• (36:16) How to minimize the hazards of shift work
• (48:03) Blood glucose control changes throughout the day
• (54:15) Intermittent fasting vs time-restricted eating
• (01:24:41) TRE improves exercise performance and muscle gain
• (01:32:33) What starts the daily eating clock?
• (01:37:32) Eating fewer meals is better
• (01:48:12) TRE improves sleep and cognition
• (01:52:41) Participate in Dr. Panda's research by visiting MyCircadianClock.org

If you're interested in learning more, you can read the full show notes here.

Join over 300,000 people and get the latest distilled information on time restricted eating straight to your inbox weekly: https://www.foundmyfitness.com/newsletter

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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.

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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

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.

In this episode, you'll discover:

• (00:00) Introduction
• (09:09) The three main nutrient signals that activate autophagy
• (20:55) The role of fasting and nutrient deprivation in autophagy
• (28:52) Exercise induces autography
• (33:07) Autophagy cleans out damaged organelles
• (35:14) Mitophagy keeps mitochondria healthy
• (39:38) Autophagy clears away neurodegenerative proteins in the brain
• (48:29) Autophagy in cancer is a double-edged sword
• (54:52) Fasting mimetics (e.g., resveratrol, spermidine, hydroxycitrate) induce autophagy

If you're interested in learning more, you can read the full show notes here.

Join over 300,000 people and get the latest distilled information on fasting & caloric restriction straight to your inbox weekly: https://www.foundmyfitness.com/newsletter

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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.

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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.

Jari Laukkanen

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.

In this episode, you'll discover:

• (00:00) Introduction
• (01:50) Sauna use improves cardiovascular health and reduces risk of death
• (06:42) How sauna use lowers blood pressure
• (08:07) Sauna use mimics aerobic exercise, increasing heart rate up to 150 beats/min
• (09:40) How long should you stay in the sauna?
• (11:59) Heat shock proteins help keep the brain healthy
• (14:52) Sauna use increases growth hormone and improves response to exercise
• (17:43) The positive effects of sauna on mood may be due to endorphins
• (20:58) Finnish sauna culture and adding cold-water immersion to the sauna experience

If you're interested in learning more, you can read the full show notes here.

Join over 300,000 people and get the latest distilled information on sauna use straight to your inbox weekly: https://www.foundmyfitness.com/newsletter

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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.

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