Targeting Cellular Senescence in Organ Transplantation

Zhou, Hao; Tullius, Stefan G.

doi:10.1097/tp.0000000000004552

Cited by 1 publication

(1 citation statement)

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“…Overall, there are a myriad of opportunities to exploit senotherapies in transplantation from stabilizing potential recipient while waiting for an organ, optimizing recipients following transplantation, improving the quality of organs by pretreatment of older donors with senotherapeutics before the donation, improving organ regeneration in older living donors and recipients, and optimizing marginal allografts (liver, kidney, heart, lung) on ex vivo perfusion devices with senotherapeutic treatment before transplantation, thus prolonging ex vivo and in vivo lifespan of donated organs (Figure 3). 31,170 In summary, CS of immune and nonimmune compartments plays a major role in chronic disease and aging. Manipulating CS to improve outcomes in transplant candidates and recipients by optimizing their overall medical condition and quality of transplanted organs is an emerging field of research.…”

Section: Application Of Emerging Therapies To Transplantationmentioning

confidence: 99%

Effect of Cellular Senescence in Disease Progression and Transplantation: Immune Cells and Solid Organs

Kirchner,

Badshah,

Hong

et al. 2023

Transplantation

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Aging of the world population significantly impacts healthcare globally and specifically, the field of transplantation. Together with end-organ dysfunction and prolonged immunosuppression, age increases the frequency of comorbid chronic diseases in transplant candidates and recipients, contributing to inferior outcomes. Although the frequency of death increases with age, limited use of organs from older deceased donors reflects the concerns about organ durability and inadequate function. Cellular senescence (CS) is a hallmark of aging, which occurs in response to a myriad of cellular stressors, leading to activation of signaling cascades that stably arrest cell cycle progression to prevent tumorigenesis. In aging and chronic conditions, senescent cells accumulate as the immune system’s ability to clear them wanes, which is causally implicated in the progression of chronic diseases, immune dysfunction, organ damage, decreased regenerative capacity, and aging itself. The intimate interplay between senescent cells, their proinflammatory secretome, and immune cells results in a positive feedback loop, propagating chronic sterile inflammation and the spread of CS. Hence, senescent cells in organs from older donors trigger the recipient’s alloimmune response, resulting in the increased risk of graft loss. Eliminating senescent cells or attenuating their inflammatory phenotype is a novel, potential therapeutic target to improve transplant outcomes and expand utilization of organs from older donors. This review focuses on the current knowledge about the impact of CS on circulating immune cells in the context of organ damage and disease progression, discusses the impact of CS on abdominal solid organs that are commonly transplanted, and reviews emerging therapies that target CS.

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Section: Application Of Emerging Therapies To Transplantationmentioning

confidence: 99%