The emergence of resistance to anti-infective agents poses a significant threat to successfully treating infections caused by bacteria. Bacteria acquire random mutations due to exposure to environmental stresses, which may increase their fitness to other selection pressures. Interestingly, for bacteria, the frequency of anti-microbial resistance (AMR) seems to be increasing in tandem with the human lifespan. Based on evidence from previous literature, we speculate that increased levels of free radicals (Reactive Oxygen Species-ROS and Reactive Nitrosative Species-RNS), elevated inflammation, and the altered tissue microenvironment in aged individuals may drive pathogen mutagenesis. If these mutations result in the hyperactivation of efflux pumps or alteration in drug target binding sites, it could confer AMR, thus rendering antibiotic therapy ineffective while leading to the selection of novel drug-resistant variants.

中文翻译：

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抗菌耐药性和老化——进化设计

抗感染药物耐药性的出现对成功治疗细菌引起的感染构成了重大威胁。细菌由于暴露于环境压力而获得随机突变，这可能会增加它们对其他选择压力的适应性。有趣的是，对于细菌来说，抗微生物药物耐药性（AMR）的频率似乎随着人类寿命的延长而增加。根据之前文献的证据，我们推测老年人体内自由基（活性氧-ROS 和活性亚硝基-RNS）水平升高、炎症加剧以及组织微环境改变可能会导致病原体突变。如果这些突变导致外排泵过度激活或药物靶标结合位点发生改变，则可能会产生 AMR，从而使抗生素治疗无效，同时导致新的耐药变体的选择。