Homoharringtonine (HHT), an FDA-approved anti-leukemic drug, has emerged as a promising candidate for senotherapeutic applications, demonstrating significant efficacy in targeting senescent cells. In a comprehensive drug-repositioning study involving 2,150 clinically applied compounds, HHT was identified for its ability to selectively eliminate senescent preadipocytes and adipocytes with minimal cytotoxicity to non-senescent cells. This selective action positions HHT as a potential therapeutic agent for addressing age-related metabolic dysfunctions, particularly those associated with white adipose tissue (WAT).

The findings highlight the critical role of senescent cells in the pathogenesis of metabolic diseases, particularly their accumulation in WAT, which correlates with functional decline and inflammation. HHT treatment not only improved WAT function and reduced inflammation in male mice but also prevented diet- and age-induced metabolic abnormalities. Mechanistically, the senotherapeutic effects of HHT are linked to its interaction with heat shock protein family A member 5 (HSPA5), underscoring a novel pathway for therapeutic intervention. Notably, HHT treatment also delayed aging and extended lifespan in progeroid and aged mice, suggesting broader implications for longevity research.

This study shifts the paradigm of drug development by reinforcing the potential of repurposing existing drugs to address age-related conditions, particularly metabolic diseases. HHT’s dual action—targeting senescent cells while preserving non-senescent cell viability—could accelerate the timeline for therapeutic applications in clinical settings. As the field moves toward integrating senotherapeutics into standard care for age-related diseases, HHT’s profile may inspire further exploration of other cancer therapies with similar mechanisms, potentially leading to more effective treatments for metabolic dysfunction and longevity enhancement.

Source: fightaging.org