Naesens Maarten
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Belgium.
Discov Med. 2011 Jan;11(56):65-75.
Cellular or replicative senescence is classically seen as the key element of aging. In renal disease and after kidney transplantation, there is increasing evidence that replicative senescence pathways (p53 and p16) play a central role in disease progression and graft outcome, independent of chronological age. In this review, we summarize the current concepts in the molecular mechanisms of cellular senescence, and correlate these theories with the available literature on aging of native kidneys, kidney diseases, and outcome of renal allografts. Recent data illustrate the complex biology of senescence in vivo, and disprove the concept that senescence is an intrinsic injury process with immanent deleterious consequences. Senescence acts as a homeostatic mechanism that can even limit renal fibrosis, at least in animal studies. In a human setting, it remains to be investigated whether cellular senescence plays an active or a bystander role in fibrogenesis and atrophy of renal tissue.
细胞衰老或复制性衰老通常被视为衰老的关键要素。在肾脏疾病及肾移植后，越来越多的证据表明，复制性衰老途径（p53和p16）在疾病进展和移植肾预后中起着核心作用，且与实际年龄无关。在本综述中，我们总结了细胞衰老分子机制的当前概念，并将这些理论与有关天然肾脏衰老、肾脏疾病及同种异体肾移植预后的现有文献进行关联。近期数据阐明了体内衰老的复杂生物学特性，并反驳了衰老乃具有内在有害后果的内在损伤过程这一概念。至少在动物研究中，衰老作为一种稳态机制，甚至可以限制肾纤维化。在人类环境中，细胞衰老在肾组织纤维化和萎缩中是发挥积极作用还是旁观者作用，仍有待研究。
