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与年轻女性相比,百岁老人的淋巴母细胞系中 ATM 的表达更高。

Higher ATM expression in lymphoblastoid cell lines from centenarian compared with younger women.

机构信息

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

出版信息

Drug Dev Res. 2022 Sep;83(6):1419-1424. doi: 10.1002/ddr.21972. Epub 2022 Jun 30.

Abstract

With increased life expectancies in developed countries, cancer rates are becoming more common among the elderly. Cancer is typically driven by a combination of germline and somatic mutations accumulating during an individual's lifetime. Yet, many centenarians reach exceptionally old age without experiencing cancer. It was suggested that centenarians have more robust DNA repair and mitochondrial function, allowing improved maintenance of DNA stability. In this study, we applied real-time quantitative PCR to examine the expression of ATM in lymphoblastoid cell lines (LCLs) from 15 healthy female centenarians and 24 younger female donors aged 21-88 years. We observed higher ATM mRNA expression of in LCLs from female centenarians compared with both women aged 21-48 years (FD = 2.0, p = .0016) and women aged 56-88 years (FD = 1.8, p = .0094. Positive correlation was found between ATM mRNA expression and donors age (p = .0028). Levels of hsa-miR-181a-5p, which targets ATM, were lower in LCLs from centenarians compared with younger women. Our findings suggest a role for ATM in protection from age-related diseases, possibly reflecting more effective DNA repair, thereby reducing somatic mutation accumulation during aging. Further studies are required for analyzing additional DNA repair pathways in biosamples from centenarians and younger age men and women.

摘要

随着发达国家预期寿命的延长,癌症在老年人中的发病率越来越高。癌症通常是由个体一生中积累的种系和体细胞突变共同驱动的。然而,许多百岁老人在没有经历癌症的情况下达到了非常高的年龄。有人认为,百岁老人具有更强的 DNA 修复和线粒体功能,从而能够更好地维持 DNA 稳定性。在这项研究中,我们应用实时定量 PCR 检测了来自 15 名健康女性百岁老人和 24 名 21-88 岁年轻女性供体的淋巴母细胞系 (LCL) 中 ATM 的表达。我们观察到,与年龄在 21-48 岁的女性(FD=2.0,p=0.0016)和年龄在 56-88 岁的女性(FD=1.8,p=0.0094)相比,LCL 中女性百岁老人的 ATM mRNA 表达更高。ATM mRNA 表达与供体年龄之间存在正相关关系(p=0.0028)。靶向 ATM 的 hsa-miR-181a-5p 在百岁老人的 LCLs 中的水平低于年轻女性。我们的研究结果表明,ATM 在保护与年龄相关的疾病方面发挥作用,这可能反映了更有效的 DNA 修复,从而减少了衰老过程中体细胞突变的积累。需要进一步研究分析百岁老人和年轻男性和女性生物样本中的其他 DNA 修复途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d011/9545764/acd0fc68fdcd/DDR-83-1419-g002.jpg

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