Windler Cordula, Gey Claudia, Seeger Karsten
Institute of Chemistry and Metabolomics, University of Lübeck, 23538Lübeck, Germany.
Institute of Biology and Institute of Physiology, University of Lübeck, 23538Lübeck, Germany.
Mech Ageing Dev. 2017 Jun;164:82-90. doi: 10.1016/j.mad.2017.05.001. Epub 2017 May 2.
Unmodified cells undergo only a limited number of cell divisions until they enter a state termed cellular senescence. Other triggers like cytotoxic compounds can also induce cell senescence. Since cell senescence represents a major mechanism of tumor suppression this cellular state has attracted increasing attention. Different markers like senescence-associated β-galactosidase (SAβGal), senescence-associated heterochromatic foci (SAHF) or certain metabolic changes have been identified to be characteristic for senescent cells; however, data is often limited to fibroblasts - the cardinal model system for cellular senescence. In order to investigate whether metabolic changes during senescence are cell type independent, skin fibroblasts and skin melanocytes have been examined. Expression of the senescence marker p16 could be detected in skin fibroblasts but not in melanocytes of this specific donor, rendering the senescent phenotype not fully ascertained for the melanocytes. Metabolic profiles of senescent cells and controls have been determined using NMR spectroscopy. Changes in metabolism are different for fibroblasts and melanocytes. Senescent melanocytes showed lower levels of phosphocholine whereas for fibroblasts in accordance with literature, levels of glycerophosphocholine were increased during senescence. Although no general metabolic marker for cellular senescence exists, the same metabolic pathway seems to be affected for both cell types.
未经修饰的细胞仅经历有限次数的细胞分裂，直到它们进入一种称为细胞衰老的状态。其他触发因素，如细胞毒性化合物，也可诱导细胞衰老。由于细胞衰老代表了肿瘤抑制的一种主要机制，这种细胞状态已引起越来越多的关注。已确定不同的标志物，如衰老相关β-半乳糖苷酶（SAβGal）、衰老相关异染色质灶（SAHF）或某些代谢变化，是衰老细胞的特征；然而，数据通常仅限于成纤维细胞——细胞衰老的主要模型系统。为了研究衰老过程中的代谢变化是否与细胞类型无关，对皮肤成纤维细胞和皮肤黑素细胞进行了检测。在该特定供体的皮肤成纤维细胞中可检测到衰老标志物p16的表达，但在黑素细胞中未检测到，这使得黑素细胞的衰老表型尚未完全确定。使用核磁共振波谱法测定了衰老细胞和对照细胞的代谢谱。成纤维细胞和黑素细胞的代谢变化不同。衰老的黑素细胞中磷酸胆碱水平较低，而对于成纤维细胞，与文献一致，衰老过程中甘油磷酸胆碱水平升高。虽然不存在细胞衰老的通用代谢标志物，但两种细胞类型的相同代谢途径似乎都受到影响。
