#333 ‒ Longevity roundtable — the science of aging, geroprotective molecules, lifestyle interventions, challenges in research, and more | Steven Austad, Matt Kaeberlein, Richard Miller

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In this special episode of The Drive, Peter introduces a brand-new roundtable format. Joined by three renowned experts in longevity science—Steven Austad, Richard Miller, and Matt Kaeberlein—the group explores the rapidly evolving field of geroscience. Together, they dive deep into topics like the relationship between healthspan and lifespan, evaluating interventions like rapamycin and senolytics, the role of epigenetic changes in aging, and whether GLP-1 receptor agonists hold geroprotective potential. They also tackle major challenges in funding and public acceptance of longevity research including how geroprotective interventions might be tested in humans. Packed with nuanced debate, humor, and groundbreaking insights, this episode is a must-listen for anyone fascinated by the science of aging.

We discuss:

• The recent rise in public interest in longevity, misconceptions, and the link between healthspan and lifespan [3:45];
• Redefining healthspan, the US healthcare paradox, and separating longevity science from commercial hype [12:30];
• The need to redirect medical research from disease-specific models to aging-focused approaches [21:30];
• Proactive healthcare: rethinking health, disease, and the role of aging [30:00];
• Biologic age versus chronologic age, and the limitations and potential of epigenetic clocks [35:00];
• The utility and drawbacks of the "hallmarks of aging" as a framework for research and funding [49:30];
• The role of epigenetic changes in aging and the challenges of proving causality [56:45];
• The translational challenges of moving aging research from preclinical studies to human applications [1:03:45];
• Distinguishing between a biomarker of aging and aging rate indicators [1:17:15];
• The difficulties of translating longevity research in mice to humans, and the difficulties of testing interventions in humans [1:21:15];
• Exercise, aging, and healthspan: does exercise slow aging? [1:35:45];
• Are GLP-1 receptor agonists geroprotective beyond caloric restriction effects? [1:41:00];
• The role of senescent cells in aging, challenges with reproducibility in studies, and differing views on the value of current research approaches [1:46:15];
• How funding challenges and leadership in NIH and other institutes impact the advancement of aging-related research [2:00:15];
• Metformin: geroprotective potential, mechanisms, and unanswered questions [2:02:30];
• Canagliflozin and rapamycin as geroprotective molecules: mechanisms, dosing strategies, and longevity potential [2:10:45];
• Resveratrol and NAD precursors—a lack of evidence for anti-aging effects [2:22:45];
• The potential of parabiosis and plasmapheresis to slow aging, the challenges in translating mouse studies to humans, and possible design for human studies [2:29:45]; and
• More.

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