Bringing Senotherapeutics from Research to Patient Care: Status and Challenges

The evolution of senotherapeutics began with first-generation senolytics targeting antiapoptotic pathways in senescent cells. More recent strategies involve marker-specific targeting, addressing the limitations of current therapies and aiming for greater precision. This has led to the development of second-generation senotherapeutics, including senoblockers (prevent senescence) and senoreversers (reverse established senescence). While still in the early to middle stages, future success depends on long-term efficacy, safety validation, and advancements in biomarker discovery, senescence heterogeneity, and precision drug design. Key developments include biomarker identification for detecting in vivo senescence, targeted therapy development with minimal toxicity, multidisciplinary integration of genetics, metabolomics, and artificial intelligence, single-cell technology to understand senescence dynamics and greater investment and global collaboration. These therapies represent a shift from disease-focused care to aging-centered, preventive medicine, with the potential to transform healthcare and usher in a new era of regenerative, longevity science.