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复制性衰老与辐射诱导衰老:基因表达谱比较

Replicative and radiation-induced aging: a comparison of gene expression profiles.

作者信息

Aliper Alexander M, Bozdaganyan Marine E, Orekhov Philipp S, Zhavoronkov Alex, Osipov Andreyan N

机构信息

Inсilico Medicine, Inc., Baltimore, MD 21218, USA.

Moscow Institute of Physics and Technology, Dolgoprudny, Russia.

出版信息

Aging (Albany NY). 2019 Apr 19;11(8):2378-2387. doi: 10.18632/aging.101921.

Abstract

All living organisms are subject to the aging process and experience the effect of ionizing radiation throughout their life. There have been a number of studies that linked ionizing radiation process to accelerated aging, but comprehensive signalome analysis of both processes was rarely conducted. Here we present a comparative signaling pathway based analysis of the transcriptomes of fibroblasts irradiated with different doses of ionizing radiation, replicatively aged fibroblasts and fibroblasts collected from young, middle age and old patients. We demonstrate a significant concordance between irradiation-induced and replicative senescence signalome signatures of fibroblasts. Additionally, significant differences in transcriptional response were also observed between fibroblasts irradiated with high and low dose. Our data shows that the transcriptome of replicatively aged fibroblasts is more similar to the transcriptome of the cells irradiated with 2 Gy, than with 5 сGy.This work revealed a number of signaling pathways that are shared between senescence and irradiation processes and can potentially be targeted by the new generation of gero- and radioprotectors.

摘要

所有生物都要经历衰老过程,并在其一生中受到电离辐射的影响。已有多项研究将电离辐射过程与加速衰老联系起来,但很少对这两个过程进行全面的信号组分析。在此,我们对用不同剂量电离辐射照射的成纤维细胞、复制性衰老的成纤维细胞以及从年轻、中年和老年患者收集的成纤维细胞的转录组进行了基于信号通路的比较分析。我们证明了成纤维细胞的辐射诱导衰老和复制性衰老信号组特征之间存在显著的一致性。此外,高剂量和低剂量照射的成纤维细胞之间在转录反应上也观察到显著差异。我们的数据表明,复制性衰老的成纤维细胞的转录组与接受2 Gy照射的细胞的转录组比与接受5 cGy照射的细胞的转录组更相似。这项工作揭示了衰老和辐射过程之间共享的许多信号通路,新一代的老年保护剂和辐射防护剂可能会针对这些通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85be/6520014/bfdade02b0c7/aging-11-101921-g001.jpg

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