Senotherapy: Implications for Transplantation.

Abstract

Cellular senescence has been identified as a potential driver of age-associated loss of organ function and as a mediator of age-related disease. Novel strategies in targeting senescent cells have shown promise in several organ systems to counteract functional decline, chronic inflammation, and age-dependent loss of repair capacity. Transgenic models have provided proof of principle that senolysis, the elimination of senescent cells, is an attractive strategy to overcome many age-related pathologies. The translation into clinical application is now possible with the emergence of drug-based senotherapies. In this review, we will discuss different senotherapeutic approaches and their modes of action. Senolytics eliminate senescent cells preferentially through the induction of apoptosis in senescent but not in normal cells, whereas senomorphics rather interact with the proinflammatory profile present in senescent cells. In the context of transplantation, the natural clearance of senescent cells might be reduced because of dysfunctional immune surveillance under immunosuppression. The transplantation setting allows for different applications of senotherapies. Conditioning donor organs before and during the ex situ phase offers the opportunity to interfere with accumulating senescence, ultimately reducing the burden of life-limiting comorbidities in chronically ill recipients.