普林斯顿大学的化学与综合基因组学教授Josh Rabinowitz在本次访谈中深入探讨了代谢组学、NAD及其前体与癌症代谢三大主题。他从代谢的基本定义出发，详细解析了葡萄糖代谢、乳酸作为燃料的角色，以及这些底物的调控机制。此外，他还阐述了电子传递链和克雷布斯循环在药物和营养方面的意义，并探讨了NAD在能量生成过程中的核心作用。最后，Josh展望了癌症代谢与免疫疗法结合可能带来的治疗希望。

🔍Josh Rabinowitz教授的研究聚焦于通过代谢物及其流量来全面理解细胞代谢。他首先定义了代谢、代谢物和流量组学，接着深入探讨了葡萄糖代谢，特别是乳酸作为替代燃料的角色及其调控。

🧬在讨论NAD及其前体时，Josh详细解释了NAD在能量生产中的关键作用，以及随着年龄增长NAD水平的下降。他还探讨了通过静脉或口服补充NMN和NR前体来提高NAD水平的有效性及其对寿命和健康期的影响。

🦄关于癌症代谢，Josh讨论了癌症代谢与免疫疗法之间的交汇点，以及如何利用癌症的代谢特性来开发新的治疗方法。他还提出了将癌症转变为慢性疾病的可能性，并展望了营养方法在癌症治疗中的潜在作用。

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Josh Rabinowitz is a Professor of Chemistry and Integrative Genomics at Princeton University, where his research focuses on developing a quantitative, comprehensive understanding of cellular metabolism through the study of metabolites and their fluxes. In this episode, Josh focuses the discussion on three main topics: metabolomics, NAD (and its precursors), and cancer metabolism. The metabolomics discussion starts with a broad definition of metabolism, metabolites, and fluxomics before diving deep into glucose metabolism, lactate as a fuel, movement of lactate, and the regulation of these substrates. He then gives a detailed explanation of the electron transport chain and Krebs cycle and their implications with respect to both drugs and nutrition while also explaining how NAD is central to the process of energy generation. He then discusses the age-related decline in NAD and what current literature says about efforts to increase NAD through intravenous or oral supplementation with the precursors NMN and NR, including whether doing so provides any advantage to lifespan or healthspan. Finally, Josh ends the conversation talking about cancer metabolism and how one particular intersection between cancer metabolism and immunotherapy might provide a hopeful outlook on the future of cancer treatment.

We discuss:

Josh’s background and unique path to becoming a research scientist at Princeton [3:30]; What sparked Josh’s early interest in metabolism [11:15]; Metabolomics 101: defining metabolites and how they are regulated [16:30]; Fluxomics: metabolism as a system in action [26:00]; The Randle Hypothesis: glucose and fatty acids compete as substrates for oxidation [33:30]; The important role of lactate as an alternate fuel [36:30]; Fasting lactate levels as a potential early indicator of metabolic dysfunction [48:00]; The beauty of the Krebs cycle and the role of NAD in energy production [53:15]; How the drug metformin acts on complex I of the electron transport chain [1:05:00]; The difference between NADH and NADPH [1:08:45]; NAD levels with age, and the efficacy of supplementing with intravenous NAD [1:10:45]; The usefulness of restoring NAD levels and efficacy of oral supplementation with NAD precursors NR and NMN [1:22:15]; Exploring the hypothesis that boosting NAD levels is beneficial [1:32:30]; Cancer metabolism and the intersection with immunotherapy [1:39:00]; Making cancer a chronic disease: exploiting the metabolic quirks of cancer, augmenting the immune system, and more [1:46:15]; The challenge of treating pancreatic cancer [1:50:30]; Epithelial cancers that might respond to metabolic approaches to therapy [1:56:30]; Josh’s hopeful outlook on the future of cancer treatment [1:59:00]; Nutritional approaches to cancer attenuation [2:00:15]; What makes Princeton University special [2:06:15]; More.

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