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

Aug 10, 2020

Joan Mannick, M.D., co-founder of Restore Bio, and Nir Barzilai, M.D., director at the Institute for Aging Research, delve into the fascinating worlds of rapamycin and metformin. They discuss how these compounds may enhance longevity and boost immune responses, particularly in reducing COVID-19 mortality. Nir shares insights from his clinical trial testing metformin's pro-longevity effects, while Joan explains rapalogs' immune-enhancing capabilities. The potential roles of these drugs in combating neurodegenerative diseases also spark engaging discussions.

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ANECDOTE

Joan Mannick's Entry into Aging Research

Joan Mannick's initial interest in aging research stemmed from Cynthia Kenyon's work on lifespan-extending genetic mutations in worms.
This led her to propose an aging study at Novartis, initially met with skepticism but later embraced by leadership.

INSIGHT

Rationale for Testing Rapamycin for Immune Enhancement

Rapamycin's clinical use as an immunosuppressant raised questions about its potential to enhance immune function.
Joan Mannick argued that human trials were necessary to see if rapamycin's beneficial effects on aging translated to immune enhancement in humans.

ANECDOTE

Nir Barzilai's Metformin Journey

Nir Barzilai's early work involved investigating metformin's mechanism of action.
He later rediscovered its potential for longevity based on various studies showing its preventive effects on age-related diseases and mortality.

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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
More.

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