Matarrese Paola, Tinari Antonella, Ascione Barbara, Gambardella Lucrezia, Remondini Daniel, Salvioli Stefano, Tenedini Elena, Tagliafico Enrico, Franceschi Claudio, Malorni Walter
Department of Drug Therapy and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Age (Dordr). 2012 Dec;34(6):1341-59. doi: 10.1007/s11357-011-9307-4. Epub 2011 Sep 9.
In the present work, we analyzed the survival features of six different Epstein-Barr virus (EBV)-stabilized lymphoid cell lines obtained from adult subjects and from subjects of more than 95 years. For the first, we found that lymphoid B cells from centenarians were more resistant to apoptosis induction and displayed a more developed lysosomal compartment, the most critical component of phagic machinery, in comparison with lymphoid B cells from adult subjects. In addition, cells from centenarians were capable of engulfing and digesting other cells, i.e., their siblings (even entire cells), whereas lymphoid cells from "control samples", i.e., from adults, did not. This behavior was improved by nutrient deprivation but, strikingly, it was unaffected by the autophagy-modulating drug, rapamycin, an autophagy inducer, and 3-methyladenine, an autophagy inhibitor. Transcriptomic analyses indicated that: (1) aspartyl proteases, (2) cell surface molecules such as integrins and cadherins, and (3) some components of cytoskeletal network could contribute to establish this survival phenotype. Also, Kyoto Encyclopedia of Genes and Genomes pathways such as Wnt signaling pathway, an essential contributor to cell migration and actin cytoskeleton remodeling, appeared as prominent. Although we cannot rule out the possibility that EBV-immortalization could play a role, since we observed this phagic behavior in cells from centenarians but not in those from adults, we hypothesize that it may represent an important survival determinant in cells from centenarians.
在本研究中，我们分析了从成年受试者和95岁以上受试者获得的六种不同的爱泼斯坦-巴尔病毒（EBV）稳定的淋巴样细胞系的存活特征。首先，我们发现，与成年受试者的淋巴B细胞相比，百岁老人的淋巴B细胞对凋亡诱导更具抗性，并且具有更发达的溶酶体区室，这是吞噬机制的最关键组成部分。此外，百岁老人的细胞能够吞噬和消化其他细胞，即它们的同类细胞（甚至是整个细胞），而来自“对照样本”（即成年人）的淋巴细胞则不能。营养剥夺可改善这种行为，但令人惊讶的是，它不受自噬调节药物雷帕霉素（一种自噬诱导剂）和3-甲基腺嘌呤（一种自噬抑制剂）的影响。转录组分析表明：（1）天冬氨酸蛋白酶，（2）细胞表面分子如整合素和钙黏着蛋白，以及（3）细胞骨架网络的一些成分可能有助于建立这种存活表型。此外，京都基因与基因组百科全书通路如Wnt信号通路（细胞迁移和肌动蛋白细胞骨架重塑的重要贡献者）也显得很突出。虽然我们不能排除EBV永生化可能起作用的可能性，因为我们在百岁老人的细胞中观察到了这种吞噬行为，而在成年人的细胞中没有观察到，但我们推测这可能是百岁老人细胞中一种重要的存活决定因素。
