Transfer of Aging: Implications for Pediatric Solid Organ Transplantation.

Abstract

Solid organ transplantation (SOT) is a life-saving intervention for pediatric patients with end-stage organ failure. Due to the limited availability of pediatric donor organs, organs from older donors are frequently utilized, increasing the risk of age-mismatched transplants. Older donor organs are linked to heightened immunogenicity, rejection rates, and impaired long-term outcomes. Emerging evidence suggests that aged donor organs may transfer senescence to pediatric recipients, accelerating aging-like processes such as frailty, cognitive decline, and organ dysfunction. Additionally, the induction of senescence could alter pediatric conditions like chronic kidney disease (CKD), juvenile idiopathic arthritis (JIA), and pediatric brain tumors which have been linked to augmented senescence. Animal models have shown that older donor organs induce senescence-associated changes in young recipients, including immune dysfunction and physical and cognitive impairments. This review highlights the role of cellular senescence in pediatric organ transplantation and discusses strategies to mitigate its impact. Therapies targeting senescence, such as senolytics, offer a potential approach to improve outcomes in pediatric recipients. Further research is needed to validate these findings in human studies and guide clinical strategies that expand the donor pool while prioritizing age-matched transplantation for pediatric patients.