Precise strategies for targeted elimination of senescent cells to combat aging and age-related diseases

Cellular senescence is a cell fate marked by a prolonged and generally irreversible cessation of the cell cycle in reaction to stressors and certain physiological events. Senescent cells accumulate with age and contribute to the pathogenesis of various age-related diseases, such as neurodegeneration and cardiovascular disorders. In this context, eliminating senescent cells has emerged as a promising therapeutic approach, giving rise to the development of senolytic agents. Nevertheless, current senolytics lack precise selectivity and may induce off-target toxicity, highlighting the need for more precise interventions. This review summarizes recent progress in targeted elimination of senescent cells, including immunotherapy, engineered extracellular vesicles, and nano-based drug delivery systems. Additionally, we introduce their potential applications across various age-related diseases, then discuss the limitations and future development directions at length. STATEMENT OF SIGNIFICANCE: As the global population ages, age-related diseases pose a significant threat to human health and socioeconomic systems. Currently, eliminating senescent cells has become a promising therapeutic strategy. However, traditional senolytics lack precise selectivity and result in off-target toxicity and considerable side effects, highlighting the importance of targeted elimination. Building upon previous contributions, our study moves the field forward because we provide a systematic overview of recent advances in targeted strategies, including immunotherapy, engineered extracellular vesicles, and nano-based drug delivery systems. These strategies employ and process biomaterials to achieve precise clearance of senescent cells. Besides, we elucidate the molecular mechanisms of action and discuss the challenges and prospects, offering insights for improving biomaterials and therapeutic strategies.