Dr. Daisy Robinton, co-founder and CEO of Oviva Therapeutics, discusses the company's innovative approach to improving women's healthspan by targeting the biology of ovarian aging. Motivated by her personal experiences and the realization that female physiology is underserved by research and medicine, Daisy outlines how menopause is a key inflection point in the acceleration of aging in women. She explains the central role of anti-Mullerian hormone (AMH) in regulating ovarian function and fertility. Oviva's lead program, a recombinant enhanced AMH protein, aims to improve IVF outcomes by synchronizing follicle growth. Excitingly, this approach could also preserve ovarian reserve to delay menopause onset, thereby extending female healthspan.

Key Topics Covered:

• Pivoting from developmental biology to found a women's health startup
• Ovaries as central regulators of female healthspan beyond reproduction
• AMH as a brake on follicle activation and loss of ovarian reserve
• Using enhanced AMH to improve egg yield in poor-responding IVF patients
• Potential of AMH-based therapy to delay menopause and slow aging
• Menopause as the single greatest known accelerator of aging
• Economic and societal impact of extending female healthspan
• Distinguishing reproductive longevity from overall women's health
• Viewing fertility as a marker of overall health and wellbeing

Dr. Noah Davidsohn, co-founder and CSO of Rejuvenate Bio, discusses the company's innovative work using gene therapies to treat age-related diseases in dogs and humans. In his conversation with host Chris Patil, he explains his recent groundbreaking study showing that partial cellular reprogramming with Yamanaka factors extended lifespan and healthspan in very old mice. Noah then outlines Rejuvenate's clinical pipeline, including targeting longevity pathways like FGF-21 for heart disease and combining TGF-beta inhibition with klotho for osteoarthritis. By choosing secreted factors deliverable with liver-targeted gene therapy, Rejuvenate hopes to circumvent delivery challenges. Noah conveys an inspiring vision of adding healthy years to dogs' and humans' lives.

Key Topics Covered:

• Rejuvenate Bio's mission to reverse aging and age-related disease
• Lifespan doubling in old mice with cyclic Yamanaka factor induction
• Controllable gene therapy system for in vivo partial reprogramming
• Choice of FGF-21 for pleiotropic effects deliverable from liver
• Lead programs for arrhythmogenic cardiomyopathy and mitral valve disease
• Advantages of treating age-related diseases first in dogs
• Combination gene therapy for osteoarthritis: TGF-beta and klotho
• Secreted proteins enable broad effects without broad delivery
• Vision of expanding healthspan by "squaring the curve"
• Potential to keep people healthy, active and productive to 100+

30 Years of Aging Biology: A Pioneer’s Perspective (Cynthia Kenyon - VP Aging Biology, Calico Labs)

Dr. Cynthia Kenyon reflects on the evolution of the longevity field over the 30 years since the publication of her groundbreaking paper, “A C. elegans mutant that lives twice as long as wild type,” a genetic analysis of one of the first single-gene mutations to extend lifespan in the worm. She recounts the initial excitement and skepticism around the idea of a pathway that regulates aging, and subsequent validation of this and related ideas in a wide range of model organisms. She also discusses her longstanding belief in the translational potential to improve human healthspan, and her experience as a co-founder of one of the first longevity biotech startups, Elixir Pharmaceuticals, in 1999. Based on her unique historical perspective—and with undiminished enthusiasm—she looks ahead to the unsolved mysteries that will propel the next generation of breakthroughs.

Key ideas:

• Origins of looking at aging regulation in C. elegans in the 1990s
• age-1 and daf-2 as the first aging genes
• Early resistance to the idea of studying aging at the molecular level
• Cloning of genes to reveal conserved longevity pathways (IIS/mTOR)
• Extending lifespan in invertebrates, and then mice
• The connection between stress resistance to evolutionary theory
• Dr. Kenyon's initial belief in the translatability of aging science
• Co-founding Elixir Pharmaceuticals in 1999 to target aging
• Current optimism about interventions against aging
• Need for public funding of large trials of natural compounds
• Excitement about newest mechanisms like reprogramming
• The enduring promise of targeting core nutrient-sensing networks
• Developmental origins of aging rates and resilience

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