Abstract：
Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.
摘要：
衰老和年龄相关疾病与氧化应激和炎症错综复杂。非甾体抗炎药（NSAIDs）已显示出在减轻与年龄有关的疾病和延长各种模式生物寿命方面的希望。然而,NSAIDs在老年个体中的疗效可能受到药物代谢和耐受性的年龄相关变化的影响。这可能导致年龄依赖性毒性。本研究旨在评估与常用NSAIDs（阿司匹林，布洛芬,对乙酰氨基酚,和吲哚美辛）的寿命，healthspan,和氧化应激水平在年轻和老年秀丽隐杆线虫。结果表明，阿司匹林和布洛芬能够通过抑制ROS的产生和增强抗氧化SOD基因的表达来延长幼龄蠕虫的寿命。相比之下,对乙酰氨基酚和吲哚美辛加速了老蠕虫的衰老过程，通过pmk-1/skn-1途径导致氧化应激损伤并降低对热应力的抵抗力。值得注意的是,当pmk-1（km25）菌株中pmk-1被敲除时，对乙酰氨基酚和吲哚美辛的有害作用得以减轻。这些结果强调了由于老年人对毒性的敏感性增加，对乙酰氨基酚和吲哚美辛可能缺乏益处。进一步的研究对于阐明驱动这些年龄依赖性反应的潜在机制以及评估与老年人群使用NSAID相关的潜在风险至关重要。
