FoundMyFitness

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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Direct download: eric_verdin_1.mp3
Category:general -- posted at: 1:02am EST

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.

Direct download: satchin_panda_2.mp3
Category:general -- posted at: 4:51pm EST

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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Watch the full video on YouTube.

 

 

Direct download: kroemer_1.mp3
Category:general -- posted at: 8:55pm EST

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!
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Direct download: laukkanen_1.mp3
Category:general -- posted at: 3:52pm EST

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, 67, 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.

 

Direct download: campisi_1.mp3
Category:general -- posted at: 11:22pm EST

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.

Direct download: lithgow_1.mp3
Category:general -- posted at: 3:39pm EST

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

Direct download: refined_sugar_1.mp3
Category:general -- posted at: 9:41pm EST

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:

Genetics resources:

Direct download: saturated_fat_solocast_1.mp3
Category:general -- posted at: 5:36pm EST

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:

 

Direct download: meat_solocast_1.mp3
Category:general -- posted at: 10:58pm EST

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:

Direct download: depression_solocast_1.mp3
Category:general -- posted at: 12:30am EST