Absence of replicative senescence in cultured cells from the short-lived killifish Nothobranchius furzeri
Absence of replicative senescence in cultured cells from the short-lived killifish Nothobranchius furzeri
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DOI：
10.1016/j.exger.2012.02.012
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发表时间：
2013-01-01
影响因子：
3.9
通讯作者：
Englert, Christoph
中科院分区：
文献类型：
--
作者：
Graf, Michael;Hartmann, Nils;Englert, Christoph
年龄研究的一个主要挑战是缺乏寿命短的脊椎动物模式生物。绿松石鳉鱼Nothobranchius furzeri的寿命是已知的最短的脊椎动物，可以在人工饲养。短寿命的GRZ菌株仅达到3-4个月的最大年龄，而其他菌株（MZM）达到6-10个月。最重要的是，短寿命与典型的衰老迹象有关。为了更多地了解可能导致短寿命和菌株之间寿命差异的可能细胞因素，我们分析了细胞衰老标志物的表达。皮肤中Tp 53、Cdkn 1 a和Cdkn 2a/B的表达显示，随着年龄的增长，短寿命GRZ没有变化，但长寿命MZM株中细胞周期抑制剂Cdkn 1 a和Cdkn 2a/B的表达增加。这表明，不同的细胞周期抑制剂的表达反映了N. furzeri。为研究细胞体外寿命与生物体寿命的关系，建立了原代细胞培养模型。对于这两种菌株，我们在这里证明了复制衰老的情况下，通过形态学，Cdkn 1a和Cdkn 2a/B，群体倍增时间和γ H2 AFX在长期和短期培养细胞中的表达分析。我们认为这是由于持续的端粒酶活性和维持的端粒长度。因此，我们认为不同N. furzeri菌株之间的差异并不反映在各自培养细胞的增殖速度或复制潜力的差异上。(C)2012 Elsevier Inc. All rights reserved.
A major challenge in age research is the absence of short-lived vertebrate model organisms. The turquoise killifish Nothobranchius furzeri has the shortest known lifespan of a vertebrate that can be bred in captivity. The short lived GRZ strain only reaches a maximum age of 3-4 months, whereas other strains (MZM) reach 6-10 months. Most importantly, the short lifespan is associated with typical signs of ageing. To find out more about possible cellular factors that might contribute to the short lifespan and to the difference in lifespan between strains, we analyzed the expression of markers for cellular senescence. Expression of Tp53, Cdkn1a and Cdkn2a/b in skin revealed no change in the short-lived GRZ but increased expression of the cell cycle inhibitors Cdkn1a and Cdkn2a/b in the long-lived MZM strain with age. This suggests that expression of distinct cell cycle inhibitors reflects rather chronological than biological age in N. furzeri. To study the relationship of organismal life span and in vitro life span of cells, we established a primary cell culture model. For both strains we demonstrate here the absence of replicative senescence as analysed by morphology, expression of Cdkn1a and Cdkn2a/b, population doubling times and gamma H2AFX in long-term and short-term cultured cells. We reason this to be on account of sustained telomerase activity and maintained telomeric length. Hence, we propose that differences in maximum life span of different N. furzeri strains is not reflected by differences in proliferation speed or replicative potential of the respective cultured cells. (C) 2012 Elsevier Inc. All rights reserved.