Wednesday, October 21, 2020
Mitochondrial Health

#123–Joan Mannick & Nir Barzilai: Rapamycin and metformin—longevity, immune enhancement, & COVID-19

In this episode, Joan and Nir discuss their extensive research into rapamycin (including the category of analogs to rapamycin known as rapalogs) and metformin, respectively. Based on his work with metformin, Nir shares how he believes it could be a pro-longevity drug and the clinical trial he’s leading to test this belief. Joan discusses her work with rapalogs, their ability to suppress the immune system as well as provide immune-enhancement, and the clinical trials she has led that inform her insights. We also talk about the potential beneficial roles of both metformin and rapamycin in reducing mortality from COVID-19, reducing the risk of neurodegenerative diseases, and delaying aging as well as its related diseases.

We discuss:
-Joan’s career, interest in aging, and work with rapamycin analogs [3:45];
-When Nir became convinced metformin could be a pro-longevity agent [15:00];
-How metformin and rapamycin impact the hallmarks of aging and extend lifespan [24:15];
-Enhancing the immune system with rapalogs and metformin [34:15];
-Potential of metformin and rapamycin in reducing mortality from COVID-19 [41:30];
-Insights from Joan’s studies investigating the immune-enhancing effects of rapalogs [59:30];
-Vaccines and treatments strategies for COVID-19, and the likelihood of long-term immunity [1:08:15];
-The potential role of rapalogs and metformin in neurodegenerative disease [1:14:30];
-Nir’s TAME trial—primary objectives and latest updates [1:18:00];
-Potential synergistic effect when combining metformin with rapamycin [1:25:45];
-Why Peter stopped taking metformin and started taking rapamycin [1:27:30];
-Story from Nir’s book that demonstrates the challenge of doing good scientific studies [1:37:30];
-The biology of aging—epigenetic clocks, proteomics, and Nir’s centenarian data [1:42:00];
-Joan’s dream experiment to test immune-enhancing effect of RTB101 [1:57:15];
-Concluding thoughts on COVID-19 [1:59:45]; and

Show notes page:

The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 10 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more.

Peter is the founder of Attia Medical, PC, a medical practice with offices in San Diego and New York City, focusing on the applied science of longevity. The practice applies nutritional biochemistry, exercise physiology, sleep physiology, techniques to increase distress tolerance, lipidology, pharmacology, and four-system endocrinology to increase lifespan (delaying the onset of chronic disease), while simultaneously improving healthspan (quality of life).

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10 thoughts on “#123–Joan Mannick & Nir Barzilai: Rapamycin and metformin—longevity, immune enhancement, & COVID-19
  1. Peter! Unrelated, but I listened to your podcast with Joe Rogan and was wondering how you transitioned from engineering to medicine. Can you elaborate on that in some form or direct me to where you talked about that? i.e. did you work an engineering job, then take MCAT while working, quit your job, go to med school… etc

  2. Do we know anything about the 200 gene expressions that change as women age versus the 560 genes that change in men?

    Regarding the 46m/59m mark on how low-dose rapamycin seems to help vaccine / the immune-system by better regulating interferon, while larger doses inhibit the immune system and therefore maybe helpful once there's a cytokine storm.. sounds much like the risk-management of using 500mg of quercetin or 250mg of hydroxychloroquine, 25mg zinc and zithromax, the prevention upside seems much greater than any downside. So one is best protected while actively taking 1500mg metformin (spread throughout the day) and low-dose Afinitor (everolimus) / rtb101 (rapalog).. where rtb101 is an atp competitive inhibitor instead of an allosteric inhibitor.. what would be the dosing schedule?

    Also enjoyed the episode with Stanley Perlman on how to prepare for the next outbreak (1h3m) as well as the strategy discussed here (2h3m).. however, is there any reason why no ever seems to mention investing in antibody cloning machines. It would seem, having an army of machines cranking out antibodies from recovered patients, could help those most seriously affected. Do the antibodies not transfer well?


    What determines a person's longevity? According to the information space diagnostics ISD (, the lifetime depends, if a person is not sick, on the structure of water in the blood. Blood with old water in 66 water molecules in a cluster promotes the adhesion of red blood cells, which reduces the delivery of oxygen to blood cells. Old water is consumed by 99.9% of the people on Earth. If a person leads a correct lifestyle, then he will live 100 years. However, in some places on Earth there is water with 44 water molecules in a cluster. When consumed, such water in the blood reduces the adhesion of erythrocytes, there is more oxygen in the cells, biochemical processes in the cells are activated, and a person, with the right lifestyle, can live up to 122 years. One of the silicon minerals changes the structure of water. Hundreds of thousands of people on Earth live in such places.

    However, there is another unique structure of water with 33 water molecules in a water cluster, which allows a person to live up to 182 years with a correct lifestyle. This is achieved by the fact that erythrocytes with such a structure of water in the blood do not stick together. ISD found a substance that converts old water into the specified unique water structure. Such a substance is L type stabilized malic acid (SMA). Malic acid of the L type exists in nature and technically, but it does not change the structure of water and does not have the ability to increase longevity due to the fact that it has its structure in water in 12 acid molecules in a cluster. ISD found a technology for converting ordinary malic acid into SMA with 9 acid molecules in a cluster, with such a structure, if we take a few drops of concentrated SMA with water, the structure of water in the blood will change and will correspond to the structure with 33 water molecules in a water cluster in the blood. If you regularly take such activated water, the life expectancy increases to 182 years. In addition, SMA has another unique property – it suppresses pathogenic viruses, bacteria, fungi, blue-green algae in the body, i.e. relieves a person from disease.

    Ermakov P, professor

  4. I love this stuff. Thanks for putting it out there Peter. I put myself on metformin even though I never have elevated bg or a1c and immediately pushed the needle on weight loss where I had been stuck. It also helped me move more easily into getting ketotic, now I cycle it. My next step is going to be adding rapamycin but I'm still considering the dose and how to cycle it. I'm so glad this information is available in a digital and digestible format. No time to sit and read!

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