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Lloyd Klickstein is the Chief Science Officer at resTORbio, a biopharmaceutical company that develops medications to target the biology of aging. In this episode, Lloyd discusses his company\u2019s clinical application of rapamycin and its derivatives. He also elucidates details of his 2014 paper\u2014a paper that greatly influenced Peter\u2019s perspective of rapamycin in the context of longevity. Peter and Lloyd go on to discuss the dose-dependent effect of rapamycin on immune function and compare rapamycin, fasting, and caloric restriction. \xa0 We discuss:

• His background and decision to leave academia for translational medicine [6:15];
• Translational medicine\u2014bridging the gap between basic science and clinical medicine [10:30];
• What prompted Lloyd to focus on mTOR inhibition? [18:00];
• Defining mTOR, TORC1, and TORC2, and the consequences of inhibiting them with rapamycin [21:30];
• Dose-dependent impact of rapamycin on immune function, mTOR inhibition, and toxicity [42:15];
• Lloyd\u2019s 2014 experiment\u2014mTOR inhibition improves immune function in the elderly [53:00];
• Insights into autophagy, antigen presentation, and the pleiotropic benefits of a rapalog, and how it compares to fasting [1:13:00];
• Lloyd\u2019s 2018 experiment\u2014TORC1 inhibition enhances immune function and reduces infections in the elderly [1:18:45];
• Creation of resTORbio, subsequent studies, and takeaways about dosing, TORC2 inhibition, and tissue selectivity [1:29:00];
• Comparing the longevity effect of rapamycin, fasting, and caloric restriction [1:40:00];
• Excitement around RTB101\u2014resTORbio\u2019s mTOR inhibiting molecule [1:47:00];
• Identifying rapalogs selective for TORC1 [1:56:15];
• Treating depression with ketamine, an activator of mTOR [2:00:00];
• Epigenetic clocks, rapalogs, and metformin [2:03:30]; and
• More.

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