Recycling senescent cell lipids for targeted senotherapy

Abstract Senescent cells (SnCs) are increasingly recognized as key contributors to osteoarthritis, with conventional strategies centered on their elimination. However, senolytic approaches face mounting limitations, driving the need for refined interventions. Here, we exploit SnCs’ lipid metabolic signature to develop a senotherapeutic strategy. Given the universal lipid accumulation in SnCs and the dual role of lipids as both metabolic liabilities and essential lubricants, we engineer an injectable nanoliposuction hydrogel platform designed for “waste recycling”. This system removes excess lipids to mitigate senescence-associated secretory phenotype (SASP) propagation and incorporates the harvested lipids as a pivotal component of the biomimetic lubricating system, thereby alleviating mechanical allodynia and cartilage wear. This strategy circumvents potential side effects associated with direct SnCs clearance and repurposes these traditionally harmful cells as functional resources. Our findings establish a shift in the philosophy of senescence therapy, transitioning the focus from destructive ablation to spatially adaptive reallocation of metabolites.