Podcast Notes Playlist: Latest Episodes

• Our knowledge of the brain surpasses any other organ yet there’s a TON that we still don’t know about it
• “We have not made any significant progress in Alzheimer’s disease research. This is the largest failure of the biomedical research enterprise during my lifetime.”
• Today, many believe that if we find out what’s happening with Early-Onset Alzheimer’s Disease (EOAD) cases then we can cure the more common senile, older age late-onset dementia – this is NOT true (the pathologies are vastly different)
  • Even though a VERY small percentage of people that are described as having Alzheimer’s disease belong to this early-onset category, this is where over 90% of the research is focused
• The epidemiology shows that there’s no greater association with Alzheimer’s disease (or cardiovascular disease) than age
• 3 alternative Alzheimer’s disease treatment methods: Methylene blue, infrared light, and the ketogenic diet
• The health of the heart is very closely related to the health of the brain
  • Whatever you do that improves cardiovascular health will also improve brain health

In this episode, Francisco Gonzalez-Lima, a Professor of Neuroscience and Pharmacology & Toxicology, explains the vascular hypothesis of Alzheimer’s disease which says the central problem is a progressive neuronal energy crisis of impaired blood flow to the brain and impaired mitochondrial respiration. He walks us through the ways we can intervene in this process and also shares details of the exciting future of Alzheimer’s treatment and prevention.

We discuss:

• Background and interest in the brain [5:15];
• The unique nature of the human brain [9:15];
• Why we’ve made so little progress in Alzheimer’s research [23:00];
• The amyloid beta hypothesis [28:30];
• Hypometabolism in the brain leading to cognitive decline [39:30];
• Early signs of AD, and deciphering between age-related decline versus something pathologic [47:45];
• The vascular hypothesis of Alzheimer’s disease [54:00];
• The relationship between mitochondria, cytochrome c oxidase, and Alzheimer’s disease [1:08:00];
• Chronic inhibition of cytochrome c oxidase leads to chronic neurodegenerative disease [1:22:45];
• Major risk factors for AD, head trauma, and other forms of dementia [1:33:45];
• Methylene blue for treating and preventing neurodegeneration [1:38:15];
• Current standard of care for AD, and the reasons for a lack of advancement [2:01:45];
• Near infrared light as a targeted treatment for cognitive decline [2:05:30];
• The ketogenic diet as a treatment and preventative measure [2:13:15];
• Exciting future research coming from Francisco [2:13:00];
• Methylene blue for traumatic brain injuries [2:25:15]; and
• More.

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• The Central Tenants of Aging (AKA what goes bonkers when you get older)
  • Epigenetic changes
  • Changes in cell communication
  • Inflammation
  • The build-up of senescent cells
  • Protein misfolding
  • Telomere loss
  • Genomic instability
  • Metabolic changes
  • Adverse responses to amino acids and other nutrient inputs
• The Unifying Theory of Aging
  • Although the above doesn’t seem all that related, David believes he’s discovered an underlying factor. He explains:
    • The genome is digital information (it can easily be stored and read)
    • As it turns out, the genome is very much intact within older people/animals
    • People inherent epigenetic information from their parents (AKA the pattern of gene expression AKA the pattern to which certain genes are turned on/off)
      • This information acts in multiple dimensions: it adapts to what we eat/drink, if we exercise, and how much sleep we get (genes are being turned on/off ALL the time)
        • David refers to the above as “analog information”
  • “That’s the problem with aging: we don’t lose the digital information… the compact disc of our lives is still intact when we’re old, but it’s as if we have a scratched CD and cells don’t read the right genes at the right time.” 
    • In simple terms – Genes are being turned on/off when they shouldn’t be
      • Because of this, cells start losing their functionality and basically their identity (so you’d get a liver cell behaving as a neural cell)
• How confident is David that he’ll see a step function change in human longevity during his lifetime?
  • “There really hasn’t been a step function change in human longevity since the introduction of sanitation” – Peter
    • Perhaps there was also one with the introduction of antibiotics and vaccinations
  • “I’m getting more and more confident” – David

Today's episode of The Qualys is from podcast #27 – David Sinclair, Ph.D.: Slowing aging – sirtuins, NAD, and the epigenetics of aging.

The Qualys is a subscriber-exclusive podcast, released Tuesday through Friday, and published exclusively on our private, subscriber-only podcast feed. Qualys is short-hand for “qualifying round,” which are typically the fastest laps driven in a race car—done before the race to determine starting position on the grid for race day. The Qualys are short (i.e., “fast”), typically less than ten minutes, and highlight the best questions, topics, and tactics discussed on The Drive.

Occasionally, we will also release an episode on the main podcast feed for non-subscribers, which is what you are listening to now.

Learn more: https://peterattiamd.com/podcast/qualys/  

Subscribe to receive access to all episodes of The Qualys (and other exclusive subscriber-only content): https://peterattiamd.com/subscribe/ 

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• Silicon Valley culture is causing stress, health problems, and unhappiness in kids
• Insulin resistance is far more complicated than we make it out to be
• Exercise is essential for long-term functional health
• You don’t need a Ph.D. to take charge of your own health
• South Asians are the most insulin resistant population on the planet
• It’s been stated widely (because it should be), but smartphone and social media use among children/teens NEEDS to be limited 

In this episode, Dr. Ronesh Sinha, a physician, author, and educator based in Silicon Valley, shares his many insights into metabolic illness that he has gleaned from his South Asian patient population. In this conversation we focus on hyperinsulinemia, insulin resistance, metabolic dysregulation, inflammation, blood pressure, obesity, etc. and ways to address them with nutrition, sleep, exercise, stress management, and more. We also take a deep dive into insulin resistant phenotypes, evolutionary theory and geographic determinants of insulin resistance which provides insight into the genetic architecture and pathophysiology of metabolic syndrome. Additionally, we discuss the surprisingly interrelated topic of stress, and how we might be inadvertently passing this on to our children, leading to mental and physical sickness down the road.

We discuss:

• How a stubborn case of insulin resistance connected Peter with Ronesh [7:15];
  
• Ronesh’s clinical treatment focus of metabolic illnesses in South and East Asian patient populations [8:45];
  
• The distinction between visceral fat and subcutaneous fat stores [15:00];
  
• Shortcomings of a body mass index (BMI) calculator for evaluating metabolic disease risk [17:15];
  
• Cortisol and blood glucose variability [28:30];
  
• Insulin’s role in elevated blood glucose: A symptom of metabolic syndrome [33:25];
  
• Mechanistic explanations of insulin resistance (there may be more than one) [35:15];
  
• Theories on origins and evolutionary reasons for insulin resistance [40:00];
  
• The inverse relationship between the amount of brown adipose tissue and rates of insulin resistance, and the role of climate in patterns and prevalence of insulin resistance [49:50];
  
• Vitamin D levels, hyperinsulinemia, and other effects [53:45];
  
• The evolutionary benefit of being able to turn fructose into fat (and the price we are now paying for it) [58:00];
  
• The VO2 max relationship to insulin resistance and familial metabolic health [59:30];
  
• Using zone 2 fitness test to evaluate mitochondrial performance [1:01:15];
  
• Exercise for long-term functional health [1:06:00];
  
• Lifestyle changes to improve insulin resistance and other metabolic phenotypes [1:14:00];
  
• Is PCOS a manifestation of insulin resistance? [1:21:00];
  
• The impact of stress on adiposity, and Peter’s treatment regimen for overweight females resistant to typical nutritional approaches [1:23:45];
  
• How a culture of achievement and expectations can lead to undue stress, unhappiness, and health problems in our children (a Silicon Valley case study) [1:35:00];
  
• The negative impact of devices and social media on children [1:48:45];
  
• How you can help yourself, your family, and your community without being an MD or PhD [1:55:00]; and
  
• More.

Learn more: https://peterattiamd.com/

Show notes page for this episode:https://peterattiamd.com/roneshsinha/

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• With every interaction, aim to make someone’s day a little bit better
• In the world of music and art, rebellion is often what attracts a crowd
• Trust is the foundation of any successful business partnership
• An easy way to help deal with fame: think about your famous persona as a character
  • “When you go out to dinner and you’re Michael Douglas, you have to be Michael Douglas. The second you get back to the house, zip up the costume, put it in a closet, and go be who you are.”
  • Thinking about it this way makes dealing with criticism much easier:
    • When your “character” gets a bad review… they’re in the closet and it’s much easier to stomach
    • But, on the other hand, when YOU get a bad review, you can’t not take it personally
• “Try and make relationships win-win instead of win-lose”
  • Aim to always make sure the other person in the relationship gets something out of it, whether emotional, economic, or career-driven
• A quote to ponder – “Money equates to respect. If you work for free for people, you don’t get their respect.”

Legendary show-business manager, agent, and producer Shep Gordon talks sex, drugs, and rock and roll. He also shares the formula for manufacturing fame, and his unique philosophy on success, love and happiness.

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For comprehensive show notes on this episode, including a full edited transcript, go to https://fs.blog/podcast/

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"The most exciting new podcast in the startup world.” - Eric Ries, Founder and NYTimes bestselling author

Today we chat with Sam Parr, founder of “The Hustle” one of the fastest growing media companies here in America. They have talented writers who create amazing newsletters and compelling content on the most important business news and trends. It covers some really interesting topics outside of what you would normally find in a business-focused media company.

I met Sam in 2015 when I was invited to speak at their convention, Hustle Con. Actually, I'm going to be speaking again on December 2nd and 3rd of this year at Hustle Con here in the Bay Area.

Sam and I touched on a handful of interesting topics. He's not the conventional founder that raises VC funding in the Bay Area — He's done it completely differently and this conversation is just as unique as Sam has built his business.

We chat about him giving up alcohol 6 years ago, getting started in the hotdog stand business, and the way he built The Hustle with very little money. We also talked about him hitting moments with The Hustle that made him want to quit (despite its growth trajectory) and before hitting a new stride in the last 12 months. All of that and more on today’s episode with Sam.

You can email James questions directly at [email protected] or follow us on Twitter @ twitter.com/gobelowtheline — “Below the Line with James Beshara" is brought to you by Straight Up Podcasts LLC.