Strickertsson Jesper A B, Desler Claus, Rasmussen Lene Juel
Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Exp Gerontol. 2014 Aug;56:164-74. doi: 10.1016/j.exger.2014.03.024. Epub 2014 Apr 3.
The commensal floras that inhabit the gastrointestinal tract play critical roles in immune responses, energy metabolism, and even cancer prevention. Pathogenic and out of place commensal bacteria, can however have detrimental effects on the host, by introducing genomic instability and mitochondrial dysfunction, which are hallmarks of both aging and cancer. Helicobacter pylori and Enterococcus faecalis are bacteria of the gastrointestinal tract that have been demonstrated to affect these two hallmarks. These, and other bacteria, have been shown to decrease the transcription and translation of essential DNA repair subunits of major DNA repair pathways and increase production of reactive oxygen species (ROS). Defects in DNA repair cause mutations and genomic instability and are found in several cancers as well as in progeroid syndromes. This review describes our contemporary view on how bacterial infections impact DNA repair and damage, and the consequence on the mitochondrial and nuclear genomes. We argue that in the gastrointestinal tract, these mechanisms can contribute to tumorigenesis as well as cellular aging of the digestive system.
栖息于胃肠道的共生菌群在免疫反应、能量代谢乃至癌症预防中发挥着关键作用。然而,致病的和异位的共生细菌可能会对宿主产生有害影响,它们会引发基因组不稳定和线粒体功能障碍,而这两者都是衰老和癌症的特征。幽门螺杆菌和粪肠球菌是已被证明会影响这两个特征的胃肠道细菌。这些细菌以及其他细菌已被证明会降低主要DNA修复途径中必需DNA修复亚基的转录和翻译,并增加活性氧(ROS)的产生。DNA修复缺陷会导致突变和基因组不稳定,在多种癌症以及早衰综合征中都有发现。本综述描述了我们目前对于细菌感染如何影响DNA修复和损伤以及对线粒体和核基因组产生何种后果的观点。我们认为,在胃肠道中,这些机制可能会促进肿瘤发生以及消化系统的细胞衰老。