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In this “Ask Me Anything” (AMA) episode, Peter is joined by special guest, Dr. Matt Kaeberlein. Together they answer many questions around the field of aging with an emphasis on three specific molecules—NAD, metformin, and rapamycin—and their purported geroprotective qualities. They first discuss aging biomarkers and epigenetic clocks before breaking down the advantages and limitations of the most common experimental models being used today to study aging and pharmacological possibilities for extending lifespan. Next they dive deep into NAD and the much-hyped NAD precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). They compare data from NAD precursors to studies on metformin and rapamycin, assessing how they stack up against each other and using the comparison as an opportunity to illustrate how to make sense of new experimental data and make smart decisions about how to approach future research.

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We discuss:

• Logic behind comparing NAD precursors to rapamycin and metformin [3:40];
• Aging biomarkers: current state, usefulness, and future promise [7:00];
• Epigenetic clocks: definition, use case, and limitations [14:45];  
• Advantages and limitations of studying aging in non-humans and the strengths and weaknesses of different model systems [26:30];
• Aging studies: importance of control lifespans and the problems with reproducibility [34:15];
• Intro to NAD, potential role in aging, relationship to sirtuins, and more [48:15];
• NAD precursors (NR and NMN): current data [1:10:00];
• Human studies with NAD precursors [1:25:45];
• Comparing NAD lifespan data to data from metformin and rapamycin [1:28:30];
• Defining a “clean drug” and a “dirty drug” [1:38:00];
• Reason for the lack of rapamycin studies in humans compared to NAD and metformin [1:41:00];
• Ranking the geroprotective molecules in terms of risk and reward [1:48:00]; and
• More.

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