The Wild Health Take: Week One, from micronutrients to saunas

Each week Dr. Carl Seger listens to your favorite podcasts to summarize the data and give you our precision medicine take.

Who: Peter Attia’s The Drive Episode  - 204 with Nir Barzilai: Centenarians, Metformin, and Longevity

When: April 25, 2022

What: 5 Takeaways

1. Genes play a big role in aging especially between 80-100 y/o. Centenarians don’t have as many bad variants/genes. More importantly, they have good genes. And to a lesser but significant extent, the right behaviors. Genes involved are GH/IGF-1, one CETP, FOXO, TSHR, and ApoE. ApoE2 is the most validated longevity genotype.

2. Looking at centenarians, understanding the function of their IGF insulin-signaling, mTOR, MET kinase pathways is important in understanding their longevity. Animal models for longevity are thought to be good surrogates for humans as these pathways are conserved in evolution.

3. The data for APoE3 for risk of Alzheimer’s is not as detrimental as it used to be considered. Plenty of genes exist which lead to resiliency from Alzheimer and may offset risk of APoE4. Which speaks to the polygenic risk scoring being more important for prediction of risk of disease.

4. The real question is how much does lifestyle and environment matter in longevity. We think it matters, but how much is unclear. What is important is health span (which is hard to define) and people having contraction of morbidity. We think genes are important in this. We are getting closer to knowing which genes and what one can do, from a lifestyle standpoint, to improve life and health span by potentially affecting those genes with epigenetic changes and, potentially, medications.

5. Metformin is quite safe, and diabetics taking metformin have lower mortality, but there are multiple problems with these studies. Metformin can elevate lactate and may negatively affect exercise. Current TAME trial (targeting aging with Metformin) looking at patients without diabetes between 65-79 y/o looking at CVD, cancer, cognitive decline and mortality. TAME study will hopefully help with Omic studies from storing data on these patients and lead to the development of better biomarkers for aging.  In the TAME trial, they will gather genome-wide epigenetic data to evaluate changes caused by the treatment. The development of protein biomarkers from this study may be the future of how we measure aging as opposed to methylation. The biological clocks that are currently available are not accurate and use methylation, as well as other poor markers.

How does this apply: We think metformin may improve longevity but it is not clear with available evidence. We should watch for the results of the TAME trial and the subsequent Omic studies that may come out of the trial which could help with better biomarkers and interventions for improving health span.

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Who: Tara Brach’s Joy-Part 3 of Present Heart: The Universal Expressions of Love

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When: May 5, 2022

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What:  Andre Gide Quote on joy

1. What brings joy doesn’t cost much, but does require our attention. Joy is the aliveness and openness to experience life. It’s a natural instinct, but can also be cultivated. Joy and happiness are terms used interchangeably and must be experienced from the full body.
2. Sympathetic joy: When you experience joy alongside others.

1. Mary Oliver, “My work is to love the world.” Joy is seen as an obligation. It’s part of our human duty to experience and share joy with those around us.

Ask yourself the following:

What is between me and feeling more joy in my life?

What blocks me from feeling this openness?

Continuously shine a light of awareness to identify and separate these barriers.

A common barrier to experiencing joy: “If only _____ then I could be happy.” If you host this habit of thinking, it pulls you from being present with joy. Whatever you are thinking creates biochemistry within the body which creates a loop cycle. Most of our thinking has to do with believing something is missing or something is wrong. This line of thought must stop to fully experience joy. Being present from moment to moment is the training. Unconditional presence doesn’t mean we don’t seek our “if only’s”, but that your life isn’t set on dependence on them.

How do we gladden the mind?

You can do this through purposeful ways: by doing things you love to do & reflecting on what you’re grateful for. There’s a plethora of research to support how reflecting on ways you’re grateful can positively change the body/mind composition. Here's how:

Step 1: Have an experience (spontaneous or purposeful) that gladdens the mind

Step 2: Allow for the pause to occur for 15-30 seconds for the experience of joy to sink into your implicit memory.

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How: Joy is a feeling of being open and alive to each experience in life. You can work towards gladdening the mind through spontaneous activities in life and purposeful actions. We believe partaking in activities that bring you joy and sitting in that feeling will allow you to have a present heart. With a present heart, you are able to have sympathetic joy which is part of our due diligence to society. With practice, focus on purposeful ways to experience joy and pause in the feeling of joy for :15-30 to create an open heart habit.

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Who: Andrew Huberman, Ph.D. with guest Rhonda Patrick, Ph.D.

MICRONUTRIENTS FOR HEALTH & LONGEVITY

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When: May 2, 2022

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What: Cold and Heat exposure discussion (this podcast is separated into 2 parts as there are very different discussions and it is long)

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Discussion: Hormesis- the intermittent challenging of ourselves, including exposure to cold or heat, substances in plants like polyphenols & flavonols, intense physical activity, as well as caloric restriction and fasting result in improved management of life stress, normal immune system function, stem cell production, protein function in cells, DNA expression, autophagy, aging and longevity.  There is overlap between these stress responses in the mechanisms that produce the positive beneficial effects in humans.

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Cold Exposure: There is a relationship between uncoupling protein 1 (UCP1) and cold exposure.  Norepinephrine in the plasma does act as a vasoconstriction hormone and regulates molecular functions that have to do with adaptation to cold.  Shivering is an inefficient way to produce heat, a better way is to have your mitochondria produce heat, instead. This is done by activating UPC1 with norepinephrine. The activation of UPC1 uncouples the energy charge across the double membrane resulting in protons leaking out of the mitochondria, which respond by making as much energy as possible in the form of heat, instead of ATP.   As you become more adapted, you’ll stop shivering and use this form of thermogenesis instead.  Another adaptation is that you produce more mitochondria in the adipose tissue through activation of a protein called PGC1alpha.  

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Heat Exposure: Heat shock proteins are important to make sure the proteins inside of cells maintain their 3D structure and, therefore, are not prone to aggregating like amyloid plaque which is linked in Alzheimer’s disease (AD) and dementia. There are people who have SNPs in heat shock proteins who live, on average, 1 year longer for 1 allele or 2 years with 2 alleles.  The heat shock proteins are activated by stress response pathways including cold, just not as robustly.  In stress situations you have an improved ability to memorize and learn. There is a lot of overlap between moderate intensity exercise and sauna, including elevating core temperature to sweat out metals and improving blood flow. Studies show use of sauna has a great reduction risk of dementia and Alzheimer’s disease. Studies also show reduced CVD in men at dose-dependent rates.  

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How to apply this information:

For cold exposure: Even 20 seconds of exposure at 49 degree can lead to long lasting increases in epinephrine.  Rhonda does 3 minutes in a 49 degree Plunge tub with circulating water.  Longer and at higher temperatures may also be utilized.

For heat exposure: 20 minutes at greater than 170 degrees for reducing CVD. Conventional saunas are preferred over infrared saunas to achieve proper temperatures. Sauna use mimics moderate intensity exercise and is really good for those who cannot workout due to injury or immobility. Rhonda does 30 minutes at 189 degrees 4-7 days per week (results are dose-dependent, so daily is best).  If you don’t have a sauna, you can get activation of heat shock proteins at 104 degrees F for 20 minutes, from the shoulders down in hot water.

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