The Problem with Senolytics That Clinical Trials Missed | Dr Sundeep Khosla

Mayo Clinic's Dr. Sundeep Khosler discusses findings from the first major randomized controlled trial of senolytics in humans, revealing why cellular aging varies dramatically between individuals and what this means for longevity interventions.

Dr. Sundeep Khosler, a physician-researcher at the Mayo Clinic, leads some of the first human clinical trials testing senolytics for aging and age-related diseases. In this conversation, he shares critical findings from their 60-person randomized controlled trial that challenge assumptions about how we age at the cellular level.

The study revealed that senescent cell burden varies dramatically between individuals, with significant implications for who might benefit from senolytic interventions. While overall results showed modest improvements in bone formation markers, women with the highest senescent cell burden (measured through blood biomarkers) showed dramatic 60% improvements—suggesting aging interventions may require personalized approaches rather than universal protocols.

Dr. Khosler discusses the development of blood-based biomarkers for measuring senescent cell burden, explains why age 70 appears to be a critical threshold, and addresses the gap between promising animal studies and human translation. He provides evidence-based guidance on what people can do now, explains why he doesn't recommend current senolytics outside clinical trials, and discusses FDA-approved medications that may impact cellular aging as secondary benefits.

This interview offers a balanced, nuanced perspective on where senolytic research actually stands, moving beyond hype to understand both the promise and limitations of targeting senescent cells for healthspan.

🌐Links in this video

Dr Khosla's page at the Mayo Clinic https://www.mayo.edu/research/faculty/khosla-sundeep-m-d/bio-00078126

Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial

https://pubmed.ncbi.nlm.nih.gov/38956196/

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