Chevanne Marta, Calia Corinne, Zampieri Michele, Cecchinelli Barbara, Caldini Riccardo, Monti Daniela, Bucci Laura, Franceschi Claudio, Caiafa Paola
Department of Experimental Pathology and Oncology, University of Florence, Italy.
Rejuvenation Res. 2007 Jun;10(2):191-204. doi: 10.1089/rej.2006.0514.
Oxidative DNA damage has been implicated in the aging process and in some of its features such as telomere shortening and replicative senescence. Poly(ADP-ribosyl)ation is involved in many molecular and cellular processes, including DNA damage detection and repair, chromatin modification, transcription, and cell death pathways. We decided to examine the behavior of poly(ADP-ribosyl)ation in centenarians, i.e., those subjects who represent the best example of longevity having reached a very advanced age avoiding the main age-associated diseases. In this study we investigated the relationship between DNA repair capacity and poly(ADP-ribose) polymerase activity in Epstein-Barr virus-immortalized B lymphocyte cell lines from subjects of three different groups of age, including centenarians. Our data show that cells from centenarians have characteristics typical of cells from young people both in their capability of priming the mechanism of repair after H(2)O(2) sublethal oxidative damage and in poly(ADP-ribosyl)ation capacity, while in cells from old subjects these phenomena are delayed or decreased. Moreover, cells from old subjects show a constitutive expression level of both parp 1 and parp 2 genes reduced by a half, together with a reduced presence of modified PARP 1 and other poly(ADP-ribosyl)ated chromatin proteins in comparison to cells from young subjects and centenarians. Our data support the hypothesis that this epigenetic modification is an important regulator of the aging process in humans and it appears to be rather preserved in healthy centenarians, the best example of successful aging.
氧化性DNA损伤与衰老过程及其某些特征有关，如端粒缩短和复制性衰老。聚（ADP - 核糖）化参与许多分子和细胞过程，包括DNA损伤检测与修复、染色质修饰、转录和细胞死亡途径。我们决定研究百岁老人（即那些代表长寿最佳范例、年事已高却避免了主要年龄相关疾病的个体）体内聚（ADP - 核糖）化的表现。在本研究中，我们调查了来自三个不同年龄组（包括百岁老人）的受试者的爱泼斯坦 - 巴尔病毒永生化B淋巴细胞系中DNA修复能力与聚（ADP - 核糖）聚合酶活性之间的关系。我们的数据表明，百岁老人的细胞在H₂O₂亚致死性氧化损伤后启动修复机制的能力以及聚（ADP - 核糖）化能力方面具有年轻人细胞的典型特征，而老年受试者的细胞中这些现象则延迟或减弱。此外，与年轻受试者和百岁老人的细胞相比，老年受试者的细胞中parp 1和parp 2基因的组成型表达水平降低了一半，同时修饰的PARP 1和其他聚（ADP - 核糖）化染色质蛋白的含量也减少。我们的数据支持这样一种假设，即这种表观遗传修饰是人类衰老过程的重要调节因子，并且在健康的百岁老人（成功衰老的最佳范例）中似乎得到了较好的保留。
