Integrating senotherapeutics into transplantation: liver reconditioning in an aging donor pool

Abstract

Our aging population is reshaping transplantation medicine. As demand for liver transplantation continues to rise, an aging donor pool presents unique challenges, with marginal organs becoming increasingly prevalent and representing a critical yet underexploited opportunity. Current selection criteria, such as chronological age, may not fully capture organ quality. A multidimensional approach that better reflects true biological aging is now more crucial than ever. Increasing evidence indicates that senescence, a hallmark of aging, influences multiple stages of transplantation, including organ procurement and preservation. Assessing senescence could provide an objective metric for evaluating organ quality. Importantly, senescence quantification could both define organ quality and guide interventions aimed at mitigating this phenomenon. This review explores the contribution of senescence to the transplant process and evaluates emerging opportunities for senescence-based assessment and therapeutic intervention. We also highlight the potential to integrate these strategies with ex vivo machine perfusion to quantify senescence burden, deliver targeted interventions, and functionally recondition marginal grafts, thereby expanding the donor pool and improving outcomes in an aging population.