本期节目中，Peter与特别嘉宾Matt Kaeberlein博士共同探讨了关于衰老领域的问题，重点分析了NAD、二甲双胍和雷帕霉素这三种分子的抗衰老特性。他们讨论了衰老生物标志物和表观遗传钟，并剖析了当前用于研究衰老和延长寿命的实验模型的优缺点。节目深入探讨了NAD及其前体NR和NMN，比较了这些前体与二甲双胍和雷帕霉素的研究数据，并讨论了如何解读新实验数据，为未来的研究方向做出明智决策。

🧬 NAD及其前体NR和NMN在延缓衰老中的作用被详细讨论，它们如何影响衰老过程以及与长寿蛋白sirtuins的关系得到阐述。

🔬 节目对比了NAD前体与二甲双胍和雷帕霉素的研究数据，分析了它们在抗衰老效果上的优劣。

🧪 节目还讨论了非人类模型系统在研究衰老中的优势和局限性，以及控制寿命实验的重要性和可重复性问题。

💊 分析了“干净药物”与“脏药物”的定义，并探讨了为什么雷帕霉素在人类研究中的数量少于NAD和二甲双胍。

📈 最后，节目对这三种分子的抗衰老效果进行了风险与收益的排名。

View the Show Notes Page for This Episode

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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.

If you’re not a subscriber and listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or on our website at the AMA #35 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

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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