Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, The Netherlands.
Pharmacol Res. 2018 Apr;130:322-330. doi: 10.1016/j.phrs.2018.02.015. Epub 2018 Feb 19.
Kidney transplants from aged donors are more vulnerable to ischemic injury, suffer more from delayed graft function and have a lower graft survival compared to kidneys from younger donors. On a cellular level, aging results in an increase in cells that are in a permanent cell cycle arrest, termed senescence, which secrete a range of pro-inflammatory cytokines and growth factors. Consequently, these senescent cells negatively influence the local milieu by causing inflammaging, and by reducing the regenerative capacity of the kidney. Moreover, the oxidative damage that is inflicted by ischemia-reperfusion injury during transplantation can induce senescence and accelerate aging. In this review, we describe recent developments in the understanding of the biology of aging that have led to the development of a new class of therapeutic agents aimed at eliminating senescent cells. These compounds have already shown to be able to restore tissue homeostasis in old mice, improve kidney function and general health- and lifespan. Use of these anti-senescence compounds holds great promise to improve the quality of marginal donor kidneys as well as to remove senescent cells induced by ischemia-reperfusion injury. Altogether, senescent cell removal may increase the donor pool, relieving the growing organ shortage and improve long-term transplantation outcome.
与来自年轻供体的肾脏相比，老年供体的肾脏移植更容易受到缺血性损伤，更容易出现移植物功能延迟，并具有较低的移植物存活率。在细胞水平上，衰老会导致处于永久细胞周期停滞的细胞（称为衰老细胞）数量增加，这些细胞会分泌一系列促炎细胞因子和生长因子。因此，这些衰老细胞通过引发炎症老化和降低肾脏的再生能力，对局部环境产生负面影响。此外，移植过程中缺血再灌注损伤造成的氧化损伤可诱导衰老并加速衰老。在这篇综述中，我们描述了对衰老生物学的最新理解，这些理解导致了一类旨在消除衰老细胞的新型治疗药物的开发。这些化合物已经被证明能够恢复老年小鼠的组织内稳态，改善肾功能和整体健康状况和寿命。使用这些抗衰老化合物有望改善边缘供体肾脏的质量，并消除缺血再灌注损伤引起的衰老细胞。总之，清除衰老细胞可能会增加供体库，缓解日益增长的器官短缺问题，并改善长期移植效果。
