The podcast explores why evolution has not optimized for extended human lifespan, citing factors like early reproductive success, high environmental hazard rates, and genomic constraints. It then transitions into how modern science, particularly through epigenetic reprogramming using transcription factors, may be able to reverse cellular aging. Challenges in identifying effective transcription factor combinations and delivering them safely are discussed, with a focus on emerging technologies like lipid nanoparticles and viral vectors. The conversation also covers synthetic transcription factors and their potential to push cells into rejuvenated, non-native states. In drug discovery, the hosts examine Eroom’s Law—the trend of declining R&D productivity—and how virtual cell models could help accelerate progress. Finally, the discussion touches on the economic challenges of pharmaceutical development and the potential for long-term healthspan interventions to reshape healthcare economics by reducing chronic disease burden.