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The University of South Dakota Sanford School of Medicine, United States
Title:Lysosomal Dysfunction as a Central Driver of Age-Related Decline
Long overlooked as simple recycling organelles, lysosomes are emerging as central drivers of cellular health and aging. As the field advances toward a systems-level understanding of aging, evidence increasingly points to lysosomal dysfunction as a unifying driver behind many cellular features of aging such as autophagic failure, mitochondrial dysfunction, chronic inflammation, and impaired metabolism. Rare lysosomal storage disorders caused by genetic deficiencies in lysosomal proteins offer striking models of premature aging, and unexpected clues for intervention and prevention. These conditions expose the downstream consequences of lysosomal collapse with striking clarity, and their effective rescue through pharmacologic and genetic interventions suggests untapped therapeutic potential for healthy aging. This presentation will explore strategies for restoration of lysosomal function through hormetic pathways, enhancement of turnover and substrate clearance, and improvement of catabolic efficiency. By identifying and developing these drugs in LSDs as models of accelerated aging, such an approach could unlock new opportunities for translation to the treatment of age-related cellular dysfunction. By reframing lysosomes not as peripheral players but as master regulators of cellular resilience, this approach has the potential to reveal an entirely new class of gerotherapeutics.
Dr. Jon Brudvig is a neuroscientist and translational drug developer with over a decade of experience turning lab discoveries into real-world therapies. Dr. Brudvig has led drug discovery and development programs at Sanford Research and Amicus Therapeutics, where he has focused on rare pediatric diseases that accelerate aging at the cellular level lysosomal storage disorders.
His research spans basic lysosome biology, biomarker discovery, and therapies ranging from activators of the lysosomal stress response to gene therapies to small molecule chaperones and stabilizers of lysosomal enzymes. He has a deep interest in how drugs developed for targeted indications might be repurposed more broadly to optimize longevity in healthy individuals.
Dr. Brudvig has authored dozens of high impact publications journals such as Geroscience, JCI, and Molecular Therapy and has presented his work at hundreds of national and international conferences. He also serves on a diverse set of editorial and scientific advisory boards, contributes as a member of the International Rare Disease Research Consortium’s Task Force on Preventive Medicines, and teaches graduate courses at the University of South Dakota Sanford School of Medicine.
Dr. Brudvig is a passionate advocate for systems-level approaches to aging, bridging rigorous science with practical strategies to extend healthspan with repurposed and novel therapeutics. At GLF 2026, he will share new insights from the intersection of lysosomal therapeutics and longevity science.