At the Longevity Summit Dublin 2024, Alexander Fedintsev, Chief Science Officer at Radical Life Extension Group, delivered a keynote on measuring and treating clonal hematopoiesis. His talk highlighted how this age-related condition accelerates cardiovascular diseases and cancer risks, contributing to "inflammaging." He emphasized the potential of anti-inflammatory strategies, particularly targeting IL-6, as a promising avenue for combating the adverse effects of clonal hematopoiesis and improving longevity outcomes.

Key Points:

• Understanding Clonal Hematopoiesis (CHIP): Alexander Fedintsev introduced clonal hematopoiesis, a condition where certain mutated blood stem cells outcompete healthy ones, leading to an accumulation of damaged cells in the bloodstream. This is a common age-related phenomenon and is associated with increased risks of cardiovascular diseases, cancers, and inflammatory conditions.
• The Impact of CHIP on Ageing and Longevity: Fedintsev discussed how CHIP exacerbates cardiovascular diseases by shifting the balance of blood cell production towards pro-inflammatory myeloid cells, contributing to "inflammaging"—a chronic, low-level inflammation associated with ageing. This condition is seen in almost all people who live to 100 or older.
• Inflammation and Its Role in CHIP Progression: Inflammatory conditions accelerate the proliferation of mutated stem cells, creating a vicious cycle that favours the growth of these pathogenic clones. Fedintsev highlighted the potential role of glycation (a process where sugar molecules bind to proteins, fuelling inflammation) in promoting this process.
• CHIP's Connection to Epigenetic Age: CHIP is closely linked to higher epigenetic age—meaning individuals with CHIP often exhibit biological markers of ageing that surpass their chronological age. This is primarily due to mutations in genes related to DNA methylation.
• Potential Treatments for CHIP: While Fedintsev acknowledged that fully eradicating clonal hematopoiesis might be challenging, he proposed two strategies: targeting and eliminating mutated cells (though this may be risky) or using anti-inflammatory treatments to slow down the proliferation of these clones. He highlighted promising research involving the inhibition of the inflammatory cytokine IL-6 in rhesus monkeys.
• Ongoing Research and Future Directions: Fedintsev and his team are working on small molecule interventions to reduce inflammation and slow down CHIP in human volunteers. The aim is to suppress harmful clones while preserving overall immune function, paving the way for potential treatments to improve ageing outcomes.