Ermolaeva Maria A, Dakhovnik Alexander, Schumacher Björn
Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD) and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD) and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
Ageing Res Rev. 2015 Sep;23(Pt A):3-11. doi: 10.1016/j.arr.2014.12.009. Epub 2015 Jan 3.
The maintenance of the genome is of pivotal importance for the functional integrity of cells and tissues. The gradual accumulation of DNA damage is thought to contribute to the functional decline of tissues and organs with ageing. Defects in multiple genome maintenance systems cause human disorders characterized by cancer susceptibility, developmental failure, and premature ageing. The complex pathological consequences of genome instability are insufficiently explained by cell-autonomous DNA damage responses (DDR) alone. Quality control pathways play an important role in DNA repair and cellular DDR pathways. Recent years have revealed non-cell autonomous effects of DNA damage that impact the physiological adaptations during ageing. We will discuss the role of quality assurance pathways in cell-autonomous and systemic responses to genome instability.
基因组的维持对于细胞和组织的功能完整性至关重要。DNA损伤的逐渐积累被认为是导致组织和器官功能随衰老而衰退的原因。多种基因组维持系统的缺陷会导致人类疾病，其特征为易患癌症、发育失败和早衰。仅靠细胞自主的DNA损伤反应（DDR）不足以解释基因组不稳定的复杂病理后果。质量控制途径在DNA修复和细胞DDR途径中发挥着重要作用。近年来发现，DNA损伤具有非细胞自主效应，会影响衰老过程中的生理适应。我们将讨论质量保证途径在细胞自主和全身对基因组不稳定反应中的作用。
